Heart of the Matter

A good way to survive an acute myocardial infarction is to go to the best hospital.

Some patients seem to have found out where those are. For those of us who want to know where to go and what to look for, a recent analysis of 800,000 Medicare patients admitted with acute myocardial infarction (AMI) and heart failure in 10,000 hospitals between 2008 and 2009 provides some reassuring news (National Bureau of Economic Research Working Paper 21603). Its findings indicated that in an era when health care choice is seemingly influenced by testimonial TV ads and the creation of hospitals that look like hotels, technical medical quality outranks all the glitz and bricks. Quality was measured by hospital mortality, 30-day readmissions, adherence to well-established guidelines, and patient satisfaction questionnaires. The investigators measured the effect that medical quality and the “comfort quotient” had on the growth of hospital patient volume through the emergency departments and interhospital referrals.

Hospital admissions increased in hospitals with the highest-quality performance. Over the 2-year period, the hospitals with the highest-quality performance had increases in hospital volume. Hospitals with a 1% improvement in the adjusted AMI mortality had a 17% increase in market share and a 1.5 % growth rate.

The authors estimated that patients with an AMI (or their family) were willing to travel an additional 1.8 miles for an ED admission to a hospital with a higher survival rate, and 34 miles further for a transfer to a hospital with a higher survival rate. When patients had the option to choose a hospital to be transferred to for further care, quality of care measures had an even greater impact on choice. Postdischarge evaluation of patient satisfaction had little or no effect on growth.

Patients admitted through the ED have the least chance for hospital choice, but even in these patients knowledge about quality influenced the choice of the hospital and the long-term hospital growth rate. Considering the fact that there is scant information available either to patients or even doctors about quality measures, there appears to be a choice process either by patient family, doctor, or ambulance driver to direct patients to the hospital with the best survival rate.

How they made those decisions is not clear. Comparative hospital survival data are rarely transmitted to staff physicians and are not widely available to the public. I have never seen any data like these in the multitude of hospital TV ads, yet somehow those numbers, real or perceived, affected admission and transfer. Maybe it’s just reputation; we all know about that. If you are really interested, you can find hospital medical quality and patient experience data at Medicare’s Hospital Compare site.

All this is good. Medical quality wins. Other studies, however, suggest that usually the “comfort quotient” and measures of medical quality are more closely linked. It has also been suggested that volume is the driving force for the improvement in both quality measures by providing the resources and logistics for better care. Whatever the mechanism, it seems that high-quality medical care is not a bad way to choose which neighborhood hospital to go to in order to survive an AMI.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

A good way to survive an acute myocardial infarction is to go to the best hospital.

Some patients seem to have found out where those are. For those of us who want to know where to go and what to look for, a recent analysis of 800,000 Medicare patients admitted with acute myocardial infarction (AMI) and heart failure in 10,000 hospitals between 2008 and 2009 provides some reassuring news (National Bureau of Economic Research Working Paper 21603). Its findings indicated that in an era when health care choice is seemingly influenced by testimonial TV ads and the creation of hospitals that look like hotels, technical medical quality outranks all the glitz and bricks. Quality was measured by hospital mortality, 30-day readmissions, adherence to well-established guidelines, and patient satisfaction questionnaires. The investigators measured the effect that medical quality and the “comfort quotient” had on the growth of hospital patient volume through the emergency departments and interhospital referrals.

Hospital admissions increased in hospitals with the highest-quality performance. Over the 2-year period, the hospitals with the highest-quality performance had increases in hospital volume. Hospitals with a 1% improvement in the adjusted AMI mortality had a 17% increase in market share and a 1.5 % growth rate.

The authors estimated that patients with an AMI (or their family) were willing to travel an additional 1.8 miles for an ED admission to a hospital with a higher survival rate, and 34 miles further for a transfer to a hospital with a higher survival rate. When patients had the option to choose a hospital to be transferred to for further care, quality of care measures had an even greater impact on choice. Postdischarge evaluation of patient satisfaction had little or no effect on growth.

Patients admitted through the ED have the least chance for hospital choice, but even in these patients knowledge about quality influenced the choice of the hospital and the long-term hospital growth rate. Considering the fact that there is scant information available either to patients or even doctors about quality measures, there appears to be a choice process either by patient family, doctor, or ambulance driver to direct patients to the hospital with the best survival rate.

How they made those decisions is not clear. Comparative hospital survival data are rarely transmitted to staff physicians and are not widely available to the public. I have never seen any data like these in the multitude of hospital TV ads, yet somehow those numbers, real or perceived, affected admission and transfer. Maybe it’s just reputation; we all know about that. If you are really interested, you can find hospital medical quality and patient experience data at Medicare’s Hospital Compare site.

All this is good. Medical quality wins. Other studies, however, suggest that usually the “comfort quotient” and measures of medical quality are more closely linked. It has also been suggested that volume is the driving force for the improvement in both quality measures by providing the resources and logistics for better care. Whatever the mechanism, it seems that high-quality medical care is not a bad way to choose which neighborhood hospital to go to in order to survive an AMI.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

A good way to survive an acute myocardial infarction is to go to the best hospital.

Some patients seem to have found out where those are. For those of us who want to know where to go and what to look for, a recent analysis of 800,000 Medicare patients admitted with acute myocardial infarction (AMI) and heart failure in 10,000 hospitals between 2008 and 2009 provides some reassuring news (National Bureau of Economic Research Working Paper 21603). Its findings indicated that in an era when health care choice is seemingly influenced by testimonial TV ads and the creation of hospitals that look like hotels, technical medical quality outranks all the glitz and bricks. Quality was measured by hospital mortality, 30-day readmissions, adherence to well-established guidelines, and patient satisfaction questionnaires. The investigators measured the effect that medical quality and the “comfort quotient” had on the growth of hospital patient volume through the emergency departments and interhospital referrals.

Hospital admissions increased in hospitals with the highest-quality performance. Over the 2-year period, the hospitals with the highest-quality performance had increases in hospital volume. Hospitals with a 1% improvement in the adjusted AMI mortality had a 17% increase in market share and a 1.5 % growth rate.

The authors estimated that patients with an AMI (or their family) were willing to travel an additional 1.8 miles for an ED admission to a hospital with a higher survival rate, and 34 miles further for a transfer to a hospital with a higher survival rate. When patients had the option to choose a hospital to be transferred to for further care, quality of care measures had an even greater impact on choice. Postdischarge evaluation of patient satisfaction had little or no effect on growth.

Patients admitted through the ED have the least chance for hospital choice, but even in these patients knowledge about quality influenced the choice of the hospital and the long-term hospital growth rate. Considering the fact that there is scant information available either to patients or even doctors about quality measures, there appears to be a choice process either by patient family, doctor, or ambulance driver to direct patients to the hospital with the best survival rate.

How they made those decisions is not clear. Comparative hospital survival data are rarely transmitted to staff physicians and are not widely available to the public. I have never seen any data like these in the multitude of hospital TV ads, yet somehow those numbers, real or perceived, affected admission and transfer. Maybe it’s just reputation; we all know about that. If you are really interested, you can find hospital medical quality and patient experience data at Medicare’s Hospital Compare site.

All this is good. Medical quality wins. Other studies, however, suggest that usually the “comfort quotient” and measures of medical quality are more closely linked. It has also been suggested that volume is the driving force for the improvement in both quality measures by providing the resources and logistics for better care. Whatever the mechanism, it seems that high-quality medical care is not a bad way to choose which neighborhood hospital to go to in order to survive an AMI.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

Walking around the Cardiac Intensive Care Unit (CICU) with one of my heart failure colleagues, I was struck by the relative absence of patients with acute myocardial infarctions. Over the past 50 years, they have been replaced by patients with advanced heart failure, many of whom had been implanted with left ventricular assist devices or connected to a variety of extracorporeal support devices.

Although some of the patients were new New York Heart Association class IV patients, many had been treated for years with beta-blockers and renal ACE inhibitors or aldosterone antagonists. Their disease had now recurred and progressed despite what I had presumed to be curative drug therapy. They were experiencing the relentless progression of heart failure despite treatment that was developed almost 20 years ago and which has not advanced much since then. Many cardiologists of my generation presumed that heart failure was no longer a problem even though we knew that annual mortality rates of heart failure remained in the 10% range and that its incidence was increasing.

It has become clear to many of us that there has been little advance in the treatment of heart failure since the introduction of those 20th century drugs, notwithstanding the importance of the development of end stage cardiac support devices.

It seems our success in treating patients with ischemic heart disease had only delayed the expression and progression of cardiac dysfunction. Even with our success in treating patients with nonischemic heart failure, whatever that is, after reaching a brief plateau with drug therapy, they often experienced recurrence. It is true that many patients had improved as a result of drug therapy and that progression had been arrested and in some patients heart failure had actually been reversed. But many, like the patients I saw in our CICU, had progressed to advanced heart failure with little to be offered other than end-stage device therapy or heart transplantation. Both of these outcomes, although lifesaving, represent therapeutic failures.

It is time that we refocus our efforts on the treatment and eradication of heart failure. Although a number of contemporary treatment strategies have been developed, for the most part they have only resulted in modest additive benefit. We need to reconsider the protection of the heart during and after an ischemic event and prevent the insidious progression of ischemia in those patients with chronic coronary heart disease. In addition we need to direct our research to understand the pathophysiology of the “heart” in heart failure and to unlock the mysticism associated with the many etiologies of idiopathic nonischemic heart failure. Our knowledge in this disease or diseases is embarrassingly poor.

It is time to move on from the 20th century drug foundation of therapy based on neurohumoral control, to a 21st century understanding of the cellular and molecular targets affecting cardiac function. Recent investigations of collagen synthesis and degradation, cardiac energetics, and mitochondrial function have provided provocative information but represent only forays into the vast unknown mechanism of heart failure. The solution to worldwide heart failure is not in device therapy for everyone but in a deeper understanding of the mechanisms of heart failure and its application to therapy.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

Walking around the Cardiac Intensive Care Unit (CICU) with one of my heart failure colleagues, I was struck by the relative absence of patients with acute myocardial infarctions. Over the past 50 years, they have been replaced by patients with advanced heart failure, many of whom had been implanted with left ventricular assist devices or connected to a variety of extracorporeal support devices.

Although some of the patients were new New York Heart Association class IV patients, many had been treated for years with beta-blockers and renal ACE inhibitors or aldosterone antagonists. Their disease had now recurred and progressed despite what I had presumed to be curative drug therapy. They were experiencing the relentless progression of heart failure despite treatment that was developed almost 20 years ago and which has not advanced much since then. Many cardiologists of my generation presumed that heart failure was no longer a problem even though we knew that annual mortality rates of heart failure remained in the 10% range and that its incidence was increasing.

It has become clear to many of us that there has been little advance in the treatment of heart failure since the introduction of those 20th century drugs, notwithstanding the importance of the development of end stage cardiac support devices.

It seems our success in treating patients with ischemic heart disease had only delayed the expression and progression of cardiac dysfunction. Even with our success in treating patients with nonischemic heart failure, whatever that is, after reaching a brief plateau with drug therapy, they often experienced recurrence. It is true that many patients had improved as a result of drug therapy and that progression had been arrested and in some patients heart failure had actually been reversed. But many, like the patients I saw in our CICU, had progressed to advanced heart failure with little to be offered other than end-stage device therapy or heart transplantation. Both of these outcomes, although lifesaving, represent therapeutic failures.

It is time that we refocus our efforts on the treatment and eradication of heart failure. Although a number of contemporary treatment strategies have been developed, for the most part they have only resulted in modest additive benefit. We need to reconsider the protection of the heart during and after an ischemic event and prevent the insidious progression of ischemia in those patients with chronic coronary heart disease. In addition we need to direct our research to understand the pathophysiology of the “heart” in heart failure and to unlock the mysticism associated with the many etiologies of idiopathic nonischemic heart failure. Our knowledge in this disease or diseases is embarrassingly poor.

It is time to move on from the 20th century drug foundation of therapy based on neurohumoral control, to a 21st century understanding of the cellular and molecular targets affecting cardiac function. Recent investigations of collagen synthesis and degradation, cardiac energetics, and mitochondrial function have provided provocative information but represent only forays into the vast unknown mechanism of heart failure. The solution to worldwide heart failure is not in device therapy for everyone but in a deeper understanding of the mechanisms of heart failure and its application to therapy.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

Walking around the Cardiac Intensive Care Unit (CICU) with one of my heart failure colleagues, I was struck by the relative absence of patients with acute myocardial infarctions. Over the past 50 years, they have been replaced by patients with advanced heart failure, many of whom had been implanted with left ventricular assist devices or connected to a variety of extracorporeal support devices.

Although some of the patients were new New York Heart Association class IV patients, many had been treated for years with beta-blockers and renal ACE inhibitors or aldosterone antagonists. Their disease had now recurred and progressed despite what I had presumed to be curative drug therapy. They were experiencing the relentless progression of heart failure despite treatment that was developed almost 20 years ago and which has not advanced much since then. Many cardiologists of my generation presumed that heart failure was no longer a problem even though we knew that annual mortality rates of heart failure remained in the 10% range and that its incidence was increasing.

It has become clear to many of us that there has been little advance in the treatment of heart failure since the introduction of those 20th century drugs, notwithstanding the importance of the development of end stage cardiac support devices.

It seems our success in treating patients with ischemic heart disease had only delayed the expression and progression of cardiac dysfunction. Even with our success in treating patients with nonischemic heart failure, whatever that is, after reaching a brief plateau with drug therapy, they often experienced recurrence. It is true that many patients had improved as a result of drug therapy and that progression had been arrested and in some patients heart failure had actually been reversed. But many, like the patients I saw in our CICU, had progressed to advanced heart failure with little to be offered other than end-stage device therapy or heart transplantation. Both of these outcomes, although lifesaving, represent therapeutic failures.

It is time that we refocus our efforts on the treatment and eradication of heart failure. Although a number of contemporary treatment strategies have been developed, for the most part they have only resulted in modest additive benefit. We need to reconsider the protection of the heart during and after an ischemic event and prevent the insidious progression of ischemia in those patients with chronic coronary heart disease. In addition we need to direct our research to understand the pathophysiology of the “heart” in heart failure and to unlock the mysticism associated with the many etiologies of idiopathic nonischemic heart failure. Our knowledge in this disease or diseases is embarrassingly poor.

It is time to move on from the 20th century drug foundation of therapy based on neurohumoral control, to a 21st century understanding of the cellular and molecular targets affecting cardiac function. Recent investigations of collagen synthesis and degradation, cardiac energetics, and mitochondrial function have provided provocative information but represent only forays into the vast unknown mechanism of heart failure. The solution to worldwide heart failure is not in device therapy for everyone but in a deeper understanding of the mechanisms of heart failure and its application to therapy.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

At a time when therapeutics is emphasizing personalized therapy, it is reassuring that someone is interested in the big picture. Treating a single patient with drugs that cost $500 a pill seems in conflict with the needs of millions of individuals who might have the expression of cardiovascular disease delayed with a pill that might cost pennies.

Dr. Saleem Yusuf originated the concept of the polypill more than 10 years ago by proposing to make one simple pill to mitigate the effect of aging on cardiovascular mortality, particularly in the underdeveloped and rapidly aging countries of the world. Working at the Population Health Research Institute at the McMaster University in Canada, he has moved through a number of iterations of the original Polypill, the most recent reported from the Heart Outcomes Evaluation (HOPE-3) trial (N Engl J Med. 2016 May; 374:2021-31). HOPE-3 distilled the initial polypill array of five drugs (three antihypertensives, a statin, and an aspirin) down to a combination of three drugs; two hypertensives and a statin. One hypertension drug was discarded in the face of concerns of the potential of symptomatic hypotension, and aspirin because of its bleeding potential.

HOPE-3 included 12,705 patients in 21 countries around the world with 50% coming from Asia and China, 80% of whom were nonwhite. Patients aged at least 55 (men) and 65 (women) years with only one cardiovascular risk factor and with systolic pressure less than 160 mm Hg, were followed for 5.6 years. Patients were randomized to a combination of hypertension medications (candesartan, 16 mg, and hydrochlorothiazide, 12.5 mg), a statin (rosuvastatin, 10 mg) or both, or to placebo. The hypertension drug combination was successful in lowering the systolic pressure at randomization of 138/81 by 10 mm Hg but had no effect on cardiovascular mortality or morbidity. In contrast, the rosuvastatin arm successfully lowered the mean LDL cholesterol of 127.8 mg/dL by 26.5% at the conclusion of the trial. This was associated with a 24% decrease in the combined cardiovascular morbidity and mortality endpoint and a decrease in myocardial infarction and stroke of 35% and 30% respectively. The addition of the hypertension drugs to rosuvastatin added little to the morbidity and mortality benefit observed with rosuvastatin alone.

The initial concept of the polypill was greeted with considerable skepticism by the medical community, which has viewed attacking cardiovascular mortality as a one-on-one experience between patient and doctor. This, despite the benefit of a broad array of prevention efforts, including lifestyle and hypertension therapy that has occurred over the last half-century.

The concept of a polypill with five different medications appears to have failed, but its outcome refined to just to one statin is a message of great importance. In a universe of indigent and undertreated humans, the need for some form of intervention seems to be a crying one. The results of HOPE-3 are consistent with JUPITER and other statin lipid-lowering trials and indicates that just treating cholesterol alone in this low-risk population achieved significant benefit of itself. Application of such an intervention in the Third World could have an important benefit. The cost of such an intervention is minimal, compared with the recent additions to the cardiovascular pharmacopeia in both heart failure and lipid therapy.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

At a time when therapeutics is emphasizing personalized therapy, it is reassuring that someone is interested in the big picture. Treating a single patient with drugs that cost $500 a pill seems in conflict with the needs of millions of individuals who might have the expression of cardiovascular disease delayed with a pill that might cost pennies.

Dr. Saleem Yusuf originated the concept of the polypill more than 10 years ago by proposing to make one simple pill to mitigate the effect of aging on cardiovascular mortality, particularly in the underdeveloped and rapidly aging countries of the world. Working at the Population Health Research Institute at the McMaster University in Canada, he has moved through a number of iterations of the original Polypill, the most recent reported from the Heart Outcomes Evaluation (HOPE-3) trial (N Engl J Med. 2016 May; 374:2021-31). HOPE-3 distilled the initial polypill array of five drugs (three antihypertensives, a statin, and an aspirin) down to a combination of three drugs; two hypertensives and a statin. One hypertension drug was discarded in the face of concerns of the potential of symptomatic hypotension, and aspirin because of its bleeding potential.

HOPE-3 included 12,705 patients in 21 countries around the world with 50% coming from Asia and China, 80% of whom were nonwhite. Patients aged at least 55 (men) and 65 (women) years with only one cardiovascular risk factor and with systolic pressure less than 160 mm Hg, were followed for 5.6 years. Patients were randomized to a combination of hypertension medications (candesartan, 16 mg, and hydrochlorothiazide, 12.5 mg), a statin (rosuvastatin, 10 mg) or both, or to placebo. The hypertension drug combination was successful in lowering the systolic pressure at randomization of 138/81 by 10 mm Hg but had no effect on cardiovascular mortality or morbidity. In contrast, the rosuvastatin arm successfully lowered the mean LDL cholesterol of 127.8 mg/dL by 26.5% at the conclusion of the trial. This was associated with a 24% decrease in the combined cardiovascular morbidity and mortality endpoint and a decrease in myocardial infarction and stroke of 35% and 30% respectively. The addition of the hypertension drugs to rosuvastatin added little to the morbidity and mortality benefit observed with rosuvastatin alone.

The initial concept of the polypill was greeted with considerable skepticism by the medical community, which has viewed attacking cardiovascular mortality as a one-on-one experience between patient and doctor. This, despite the benefit of a broad array of prevention efforts, including lifestyle and hypertension therapy that has occurred over the last half-century.

The concept of a polypill with five different medications appears to have failed, but its outcome refined to just to one statin is a message of great importance. In a universe of indigent and undertreated humans, the need for some form of intervention seems to be a crying one. The results of HOPE-3 are consistent with JUPITER and other statin lipid-lowering trials and indicates that just treating cholesterol alone in this low-risk population achieved significant benefit of itself. Application of such an intervention in the Third World could have an important benefit. The cost of such an intervention is minimal, compared with the recent additions to the cardiovascular pharmacopeia in both heart failure and lipid therapy.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

At a time when therapeutics is emphasizing personalized therapy, it is reassuring that someone is interested in the big picture. Treating a single patient with drugs that cost $500 a pill seems in conflict with the needs of millions of individuals who might have the expression of cardiovascular disease delayed with a pill that might cost pennies.

Dr. Saleem Yusuf originated the concept of the polypill more than 10 years ago by proposing to make one simple pill to mitigate the effect of aging on cardiovascular mortality, particularly in the underdeveloped and rapidly aging countries of the world. Working at the Population Health Research Institute at the McMaster University in Canada, he has moved through a number of iterations of the original Polypill, the most recent reported from the Heart Outcomes Evaluation (HOPE-3) trial (N Engl J Med. 2016 May; 374:2021-31). HOPE-3 distilled the initial polypill array of five drugs (three antihypertensives, a statin, and an aspirin) down to a combination of three drugs; two hypertensives and a statin. One hypertension drug was discarded in the face of concerns of the potential of symptomatic hypotension, and aspirin because of its bleeding potential.

HOPE-3 included 12,705 patients in 21 countries around the world with 50% coming from Asia and China, 80% of whom were nonwhite. Patients aged at least 55 (men) and 65 (women) years with only one cardiovascular risk factor and with systolic pressure less than 160 mm Hg, were followed for 5.6 years. Patients were randomized to a combination of hypertension medications (candesartan, 16 mg, and hydrochlorothiazide, 12.5 mg), a statin (rosuvastatin, 10 mg) or both, or to placebo. The hypertension drug combination was successful in lowering the systolic pressure at randomization of 138/81 by 10 mm Hg but had no effect on cardiovascular mortality or morbidity. In contrast, the rosuvastatin arm successfully lowered the mean LDL cholesterol of 127.8 mg/dL by 26.5% at the conclusion of the trial. This was associated with a 24% decrease in the combined cardiovascular morbidity and mortality endpoint and a decrease in myocardial infarction and stroke of 35% and 30% respectively. The addition of the hypertension drugs to rosuvastatin added little to the morbidity and mortality benefit observed with rosuvastatin alone.

The initial concept of the polypill was greeted with considerable skepticism by the medical community, which has viewed attacking cardiovascular mortality as a one-on-one experience between patient and doctor. This, despite the benefit of a broad array of prevention efforts, including lifestyle and hypertension therapy that has occurred over the last half-century.

The concept of a polypill with five different medications appears to have failed, but its outcome refined to just to one statin is a message of great importance. In a universe of indigent and undertreated humans, the need for some form of intervention seems to be a crying one. The results of HOPE-3 are consistent with JUPITER and other statin lipid-lowering trials and indicates that just treating cholesterol alone in this low-risk population achieved significant benefit of itself. Application of such an intervention in the Third World could have an important benefit. The cost of such an intervention is minimal, compared with the recent additions to the cardiovascular pharmacopeia in both heart failure and lipid therapy.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

Recently published guidelines for the pharmacologic management of heart failure in patients with reduced ejection fraction (HFrEF) focus on two drugs – both of which have been approved by the Food and Drug Administration – that have shown promise in managing heart failure patients.

The guideline committee has deemed that the combination drug sacubitril-valsartan (Entresto, Novartis) and ivabradine (Corlanor, Amgen) as “milestone” achievements. In this reader’s mind, compared with the mortality and morbidity effect of beta-blockers and ACE inhibitors, they really don’t make it to that status. They do, however, reach the threshold of important adjuncts to the care for heart failure treatment.

Ivabradine was shown to improve the combination of rehospitalization and mortality when added to conventional therapy, including beta-blockers, by decreasing heart rate. Unfortunately, many of the patients in the trial were not adequately treated with beta-blockers. Sacubitril-valsartan, a drug we have commented about in previous columns, is interesting and adds an additional effect on mortality and morbidity when compared with enalapril alone. In the PARADIGM-HF trial, it showed a significant 20% decrease in rehospitalization and total mortality. A strong case can be made that it should be used instead of an ACE inhibitor, although it is associated with some increased hypotension and angioneurotic edema.

Sacubitril-valsartan poses a significant social issue in regard to its pricing. Most of the drugs we use for the treatment of heart failure cost less than a dollar a day when introduced, and pennies now, and they are immensely effective. Sacubitril-valsartan on average moves the mortality needle a bit, but at a cost of 20 times its competitor, enalapril. It doesn’t do it in all patients, so that it might be reasonable to use it just in those patients who are failing with an ACE inhibitor alone. This is the first time heart failure doctors have had to grapple with the problem of drug pricing, whereas the oncologist and the lipid specialists have been facing this issue for some time. Is it worth $500 a month, compared to $25 a month, to possibly move the mortality index, which has already been modified with the previous ACE inhibitors, down a bit? I suppose that the decision is up to all of us to make.

Reading the guidelines, however, provided me with some insight that I have missed in the past. Of the 17 members of the guideline writing team representing the American College of Cardiology, American Heart Association, and the Heart Failure Society of America, eight had “significant relationships” with the two pharmaceutical companies in question. Committee members were advised not to vote if they had a relevant relationship with industry. How they functioned in the committee proceeding it’s impossible to tell, but the potential for bias is there. I would imagine that eight other heart failure specialists who did not have a conflict could have been found to serve on the writing committee. As guidelines have become such a major part of the construct of the pharmacopoeia, potential bias like this should and easily can be avoided.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

Recently published guidelines for the pharmacologic management of heart failure in patients with reduced ejection fraction (HFrEF) focus on two drugs – both of which have been approved by the Food and Drug Administration – that have shown promise in managing heart failure patients.

The guideline committee has deemed that the combination drug sacubitril-valsartan (Entresto, Novartis) and ivabradine (Corlanor, Amgen) as “milestone” achievements. In this reader’s mind, compared with the mortality and morbidity effect of beta-blockers and ACE inhibitors, they really don’t make it to that status. They do, however, reach the threshold of important adjuncts to the care for heart failure treatment.

Ivabradine was shown to improve the combination of rehospitalization and mortality when added to conventional therapy, including beta-blockers, by decreasing heart rate. Unfortunately, many of the patients in the trial were not adequately treated with beta-blockers. Sacubitril-valsartan, a drug we have commented about in previous columns, is interesting and adds an additional effect on mortality and morbidity when compared with enalapril alone. In the PARADIGM-HF trial, it showed a significant 20% decrease in rehospitalization and total mortality. A strong case can be made that it should be used instead of an ACE inhibitor, although it is associated with some increased hypotension and angioneurotic edema.

Sacubitril-valsartan poses a significant social issue in regard to its pricing. Most of the drugs we use for the treatment of heart failure cost less than a dollar a day when introduced, and pennies now, and they are immensely effective. Sacubitril-valsartan on average moves the mortality needle a bit, but at a cost of 20 times its competitor, enalapril. It doesn’t do it in all patients, so that it might be reasonable to use it just in those patients who are failing with an ACE inhibitor alone. This is the first time heart failure doctors have had to grapple with the problem of drug pricing, whereas the oncologist and the lipid specialists have been facing this issue for some time. Is it worth $500 a month, compared to $25 a month, to possibly move the mortality index, which has already been modified with the previous ACE inhibitors, down a bit? I suppose that the decision is up to all of us to make.

Reading the guidelines, however, provided me with some insight that I have missed in the past. Of the 17 members of the guideline writing team representing the American College of Cardiology, American Heart Association, and the Heart Failure Society of America, eight had “significant relationships” with the two pharmaceutical companies in question. Committee members were advised not to vote if they had a relevant relationship with industry. How they functioned in the committee proceeding it’s impossible to tell, but the potential for bias is there. I would imagine that eight other heart failure specialists who did not have a conflict could have been found to serve on the writing committee. As guidelines have become such a major part of the construct of the pharmacopoeia, potential bias like this should and easily can be avoided.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

Recently published guidelines for the pharmacologic management of heart failure in patients with reduced ejection fraction (HFrEF) focus on two drugs – both of which have been approved by the Food and Drug Administration – that have shown promise in managing heart failure patients.

The guideline committee has deemed that the combination drug sacubitril-valsartan (Entresto, Novartis) and ivabradine (Corlanor, Amgen) as “milestone” achievements. In this reader’s mind, compared with the mortality and morbidity effect of beta-blockers and ACE inhibitors, they really don’t make it to that status. They do, however, reach the threshold of important adjuncts to the care for heart failure treatment.

Ivabradine was shown to improve the combination of rehospitalization and mortality when added to conventional therapy, including beta-blockers, by decreasing heart rate. Unfortunately, many of the patients in the trial were not adequately treated with beta-blockers. Sacubitril-valsartan, a drug we have commented about in previous columns, is interesting and adds an additional effect on mortality and morbidity when compared with enalapril alone. In the PARADIGM-HF trial, it showed a significant 20% decrease in rehospitalization and total mortality. A strong case can be made that it should be used instead of an ACE inhibitor, although it is associated with some increased hypotension and angioneurotic edema.

Sacubitril-valsartan poses a significant social issue in regard to its pricing. Most of the drugs we use for the treatment of heart failure cost less than a dollar a day when introduced, and pennies now, and they are immensely effective. Sacubitril-valsartan on average moves the mortality needle a bit, but at a cost of 20 times its competitor, enalapril. It doesn’t do it in all patients, so that it might be reasonable to use it just in those patients who are failing with an ACE inhibitor alone. This is the first time heart failure doctors have had to grapple with the problem of drug pricing, whereas the oncologist and the lipid specialists have been facing this issue for some time. Is it worth $500 a month, compared to $25 a month, to possibly move the mortality index, which has already been modified with the previous ACE inhibitors, down a bit? I suppose that the decision is up to all of us to make.

Reading the guidelines, however, provided me with some insight that I have missed in the past. Of the 17 members of the guideline writing team representing the American College of Cardiology, American Heart Association, and the Heart Failure Society of America, eight had “significant relationships” with the two pharmaceutical companies in question. Committee members were advised not to vote if they had a relevant relationship with industry. How they functioned in the committee proceeding it’s impossible to tell, but the potential for bias is there. I would imagine that eight other heart failure specialists who did not have a conflict could have been found to serve on the writing committee. As guidelines have become such a major part of the construct of the pharmacopoeia, potential bias like this should and easily can be avoided.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

The randomized clinical trial (RCT) has been the bulwark of the development of effective and safe medical and surgical therapy. Developed over the last half-century, they have proved the benefit and safety of new drugs and procedures and provided guidance to physicians in choosing therapeutic choices for their patients. They have replaced intuitive care that had largely directed medical care for centuries with a degree of science in making therapeutic decisions.

Although less than perfect, the RCT has been the reason for the remarkable success that we have achieved in decreasing the mortality of heart disease. This success has been driven largely by scientific altruism modified to some degree by the financial benefits of both the medical profession and the pharmaceutical industry.

As corporate hospital and third-party payers expand their role in the pattern of health care, there is the potential to make changes in how care is rendered beyond the choice of medical or surgical therapy. The expansion of care regionally and nationally provides tempting targets to modify the quality and efficacy on a large scale. It also provides potential cost-saving targets and generates corporate profits. Decisions at the corporate or administrative area in the past have been initiated on the basis of competitive costs and on intuitive decision making. The size of the market, however, provides an opportunity to test a variety of administrative plans that can lead to cost saving. These initiatives, well-meaning in their genesis, may result in patient participation in “studies” in which the patient may have a limited knowledge and benefit and uncertain risks.

RCTs demand informed consent by patients and unbiased temporal oversight by safety boards when searching for answers to questions based on contemporary knowledge. At present, there is no specific role for the patient’s voluntary and informed participation should a corporate representative initiate a “study” to answer a corporate question. Before we embark on “research” in patient care, it is imperative that we consider the principles established by RCTs. I propose two scenarios that may provide illustrative insight:

1. A nurse administrator wishes to explore the question of the cost savings achieved on a general medical ward by changing the current nurse staffing of eight professional nurses to a staffing with two professional nurses and six nursing assistants. The administrator will use personnel costs as the endpoint of the study and consider a variety of secondary issues such as the duration of time to respond to a call, sacral erythema, and wrong-dose administration, or other quality measurements.

2. The administrator of the catheterization laboratory decides to compare two catheters in the laboratory driven again by the costs of the catheters. The primary endpoint of the study will be cost savings. Secondary measurements will be time in the catheterization laboratory and postprocedure bleeding.

In both cases, the patient may or not have been informed about the research project in which they have been enrolled. In addition, there is no temporal assessment of the occurrence of adverse events that could occur during the progress of the “study” to ensure its safety. Many of the safeguards that have been developed around the RCT need to be incorporated into the design of these investigations.

This, of course, is all hypothetical, but on the other hand, it is not beyond the realm of possibility; as we move from “local care” to a system driven by anonymous personnel, it is important to obtain the consent of the patient and to establish procedures to ensure their safety.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

The randomized clinical trial (RCT) has been the bulwark of the development of effective and safe medical and surgical therapy. Developed over the last half-century, they have proved the benefit and safety of new drugs and procedures and provided guidance to physicians in choosing therapeutic choices for their patients. They have replaced intuitive care that had largely directed medical care for centuries with a degree of science in making therapeutic decisions.

Although less than perfect, the RCT has been the reason for the remarkable success that we have achieved in decreasing the mortality of heart disease. This success has been driven largely by scientific altruism modified to some degree by the financial benefits of both the medical profession and the pharmaceutical industry.

As corporate hospital and third-party payers expand their role in the pattern of health care, there is the potential to make changes in how care is rendered beyond the choice of medical or surgical therapy. The expansion of care regionally and nationally provides tempting targets to modify the quality and efficacy on a large scale. It also provides potential cost-saving targets and generates corporate profits. Decisions at the corporate or administrative area in the past have been initiated on the basis of competitive costs and on intuitive decision making. The size of the market, however, provides an opportunity to test a variety of administrative plans that can lead to cost saving. These initiatives, well-meaning in their genesis, may result in patient participation in “studies” in which the patient may have a limited knowledge and benefit and uncertain risks.

RCTs demand informed consent by patients and unbiased temporal oversight by safety boards when searching for answers to questions based on contemporary knowledge. At present, there is no specific role for the patient’s voluntary and informed participation should a corporate representative initiate a “study” to answer a corporate question. Before we embark on “research” in patient care, it is imperative that we consider the principles established by RCTs. I propose two scenarios that may provide illustrative insight:

1. A nurse administrator wishes to explore the question of the cost savings achieved on a general medical ward by changing the current nurse staffing of eight professional nurses to a staffing with two professional nurses and six nursing assistants. The administrator will use personnel costs as the endpoint of the study and consider a variety of secondary issues such as the duration of time to respond to a call, sacral erythema, and wrong-dose administration, or other quality measurements.

2. The administrator of the catheterization laboratory decides to compare two catheters in the laboratory driven again by the costs of the catheters. The primary endpoint of the study will be cost savings. Secondary measurements will be time in the catheterization laboratory and postprocedure bleeding.

In both cases, the patient may or not have been informed about the research project in which they have been enrolled. In addition, there is no temporal assessment of the occurrence of adverse events that could occur during the progress of the “study” to ensure its safety. Many of the safeguards that have been developed around the RCT need to be incorporated into the design of these investigations.

This, of course, is all hypothetical, but on the other hand, it is not beyond the realm of possibility; as we move from “local care” to a system driven by anonymous personnel, it is important to obtain the consent of the patient and to establish procedures to ensure their safety.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

The randomized clinical trial (RCT) has been the bulwark of the development of effective and safe medical and surgical therapy. Developed over the last half-century, they have proved the benefit and safety of new drugs and procedures and provided guidance to physicians in choosing therapeutic choices for their patients. They have replaced intuitive care that had largely directed medical care for centuries with a degree of science in making therapeutic decisions.

Although less than perfect, the RCT has been the reason for the remarkable success that we have achieved in decreasing the mortality of heart disease. This success has been driven largely by scientific altruism modified to some degree by the financial benefits of both the medical profession and the pharmaceutical industry.

As corporate hospital and third-party payers expand their role in the pattern of health care, there is the potential to make changes in how care is rendered beyond the choice of medical or surgical therapy. The expansion of care regionally and nationally provides tempting targets to modify the quality and efficacy on a large scale. It also provides potential cost-saving targets and generates corporate profits. Decisions at the corporate or administrative area in the past have been initiated on the basis of competitive costs and on intuitive decision making. The size of the market, however, provides an opportunity to test a variety of administrative plans that can lead to cost saving. These initiatives, well-meaning in their genesis, may result in patient participation in “studies” in which the patient may have a limited knowledge and benefit and uncertain risks.

RCTs demand informed consent by patients and unbiased temporal oversight by safety boards when searching for answers to questions based on contemporary knowledge. At present, there is no specific role for the patient’s voluntary and informed participation should a corporate representative initiate a “study” to answer a corporate question. Before we embark on “research” in patient care, it is imperative that we consider the principles established by RCTs. I propose two scenarios that may provide illustrative insight:

1. A nurse administrator wishes to explore the question of the cost savings achieved on a general medical ward by changing the current nurse staffing of eight professional nurses to a staffing with two professional nurses and six nursing assistants. The administrator will use personnel costs as the endpoint of the study and consider a variety of secondary issues such as the duration of time to respond to a call, sacral erythema, and wrong-dose administration, or other quality measurements.

2. The administrator of the catheterization laboratory decides to compare two catheters in the laboratory driven again by the costs of the catheters. The primary endpoint of the study will be cost savings. Secondary measurements will be time in the catheterization laboratory and postprocedure bleeding.

In both cases, the patient may or not have been informed about the research project in which they have been enrolled. In addition, there is no temporal assessment of the occurrence of adverse events that could occur during the progress of the “study” to ensure its safety. Many of the safeguards that have been developed around the RCT need to be incorporated into the design of these investigations.

This, of course, is all hypothetical, but on the other hand, it is not beyond the realm of possibility; as we move from “local care” to a system driven by anonymous personnel, it is important to obtain the consent of the patient and to establish procedures to ensure their safety.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

Two new drugs have arrived to challenge our prescription pad or electronic record, depending on which you use. Empagliflozin (Jardiance), a drug used to modify glucose metabolism in type 2 diabetes in patients with preexisting cardiovascular disease, demonstrated a decrease in cardiovascular mortality. The other drug, Entresto, appears to provide an added benefit in heart failure therapy and was compared with a standard ACE inhibitor.

The results of EMPA-REG OUTCOME, reported at the European Association for the Study of Diabetes meeting in Stockholm, showed empagliflozin to be the first drug to decrease the mortality and morbidity of cardiovascular disease in diabetes. It is one of a group of new sodium-glucose cotransporter 2 (SGLT-2) blockers being tested in type 2 diabetes with established cardiovascular disease. Patients were randomized to placebo or empagliflozin while receiving standard medical and cardiovascular medications. After 3 years of follow-up, patients receiving the drug experienced a lower cardiovascular mortality rate, compared with placebo patients (3.7% vs. 5.9%, a 38% reduction) in addition to a decrease in hospitalization for heart failure and death from any cause. No effect was observed on the incidence of myocardial infarction or stroke. In addition, the drug also lowered blood glucose and blood pressure and led to some significant weight loss. The drug also was shown to decrease vascular resistance and albuminuria (N Engl J Med. 2015. 373:2117-2).

Furthermore, an analysis of EMPA-REG OUTCOME presented in November at the American Society of Nephrology meeting in San Diego, showed a profound benefit on the new onset and progression of chronic renal disease in diabetes patients. The importance of these results needs emphasis. Up until recently, the Food and Drug Administration has given a pass to diabetes drugs in regard to cardiovascular endpoints; approval has been based on their primary effect on lowering blood glucose. Some drugs in the past, such as rosiglitazone, actually have shown an increase in mortality in some diabetes patients. At long last, FDA approval for diabetes drugs hinges on acceptable outcomes in cardiovascular endpoints. The addition of a drug that can actually affect cardiovascular mortality and morbidity, the major risk factor of diabetes, provides an important addition to therapy.

The other drug that provides a choice of drugs for the treatment of heart failure is Entresto, a combination of sacubitril, a neprilysin inhibitor, and the angiotensin receptor inhibitor valsartan, approved in July 2015. In PARADIGM-HF, the compound was compared to enalapril in the treatment of patients with class II, III, and IV heart failure who were also receiving beta-blockers. Entresto-treated patients reported a 21.8% incidence of the primary outcome measure, cardiovascular death and hospitalization for heart failure, compared with the enalapril alone incidence of 26.5% (P less than .001) (N Engl J Med. 2014;371:993-1004). Investigators initially excluded 11.4% of the recruited patients from the study who could not tolerate Entresto or enalapril therapy. The drugs were well tolerated without any adverse reactions during therapy. Entresto was more effective than enalapril in regards to the occurrence of heart failure and death from any cause over a 27-month average follow-up.

The observations in this study emphasize how much the mortality of heart failure has decreased over the last decade. Cardiovascular deaths have decreased to roughly 7% per year and rehospitalization occurs in about 8% in the first year. Both drugs provide an important incremental benefit in heart failure patients.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

Two new drugs have arrived to challenge our prescription pad or electronic record, depending on which you use. Empagliflozin (Jardiance), a drug used to modify glucose metabolism in type 2 diabetes in patients with preexisting cardiovascular disease, demonstrated a decrease in cardiovascular mortality. The other drug, Entresto, appears to provide an added benefit in heart failure therapy and was compared with a standard ACE inhibitor.

The results of EMPA-REG OUTCOME, reported at the European Association for the Study of Diabetes meeting in Stockholm, showed empagliflozin to be the first drug to decrease the mortality and morbidity of cardiovascular disease in diabetes. It is one of a group of new sodium-glucose cotransporter 2 (SGLT-2) blockers being tested in type 2 diabetes with established cardiovascular disease. Patients were randomized to placebo or empagliflozin while receiving standard medical and cardiovascular medications. After 3 years of follow-up, patients receiving the drug experienced a lower cardiovascular mortality rate, compared with placebo patients (3.7% vs. 5.9%, a 38% reduction) in addition to a decrease in hospitalization for heart failure and death from any cause. No effect was observed on the incidence of myocardial infarction or stroke. In addition, the drug also lowered blood glucose and blood pressure and led to some significant weight loss. The drug also was shown to decrease vascular resistance and albuminuria (N Engl J Med. 2015. 373:2117-2).

Furthermore, an analysis of EMPA-REG OUTCOME presented in November at the American Society of Nephrology meeting in San Diego, showed a profound benefit on the new onset and progression of chronic renal disease in diabetes patients. The importance of these results needs emphasis. Up until recently, the Food and Drug Administration has given a pass to diabetes drugs in regard to cardiovascular endpoints; approval has been based on their primary effect on lowering blood glucose. Some drugs in the past, such as rosiglitazone, actually have shown an increase in mortality in some diabetes patients. At long last, FDA approval for diabetes drugs hinges on acceptable outcomes in cardiovascular endpoints. The addition of a drug that can actually affect cardiovascular mortality and morbidity, the major risk factor of diabetes, provides an important addition to therapy.

The other drug that provides a choice of drugs for the treatment of heart failure is Entresto, a combination of sacubitril, a neprilysin inhibitor, and the angiotensin receptor inhibitor valsartan, approved in July 2015. In PARADIGM-HF, the compound was compared to enalapril in the treatment of patients with class II, III, and IV heart failure who were also receiving beta-blockers. Entresto-treated patients reported a 21.8% incidence of the primary outcome measure, cardiovascular death and hospitalization for heart failure, compared with the enalapril alone incidence of 26.5% (P less than .001) (N Engl J Med. 2014;371:993-1004). Investigators initially excluded 11.4% of the recruited patients from the study who could not tolerate Entresto or enalapril therapy. The drugs were well tolerated without any adverse reactions during therapy. Entresto was more effective than enalapril in regards to the occurrence of heart failure and death from any cause over a 27-month average follow-up.

The observations in this study emphasize how much the mortality of heart failure has decreased over the last decade. Cardiovascular deaths have decreased to roughly 7% per year and rehospitalization occurs in about 8% in the first year. Both drugs provide an important incremental benefit in heart failure patients.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

Two new drugs have arrived to challenge our prescription pad or electronic record, depending on which you use. Empagliflozin (Jardiance), a drug used to modify glucose metabolism in type 2 diabetes in patients with preexisting cardiovascular disease, demonstrated a decrease in cardiovascular mortality. The other drug, Entresto, appears to provide an added benefit in heart failure therapy and was compared with a standard ACE inhibitor.

The results of EMPA-REG OUTCOME, reported at the European Association for the Study of Diabetes meeting in Stockholm, showed empagliflozin to be the first drug to decrease the mortality and morbidity of cardiovascular disease in diabetes. It is one of a group of new sodium-glucose cotransporter 2 (SGLT-2) blockers being tested in type 2 diabetes with established cardiovascular disease. Patients were randomized to placebo or empagliflozin while receiving standard medical and cardiovascular medications. After 3 years of follow-up, patients receiving the drug experienced a lower cardiovascular mortality rate, compared with placebo patients (3.7% vs. 5.9%, a 38% reduction) in addition to a decrease in hospitalization for heart failure and death from any cause. No effect was observed on the incidence of myocardial infarction or stroke. In addition, the drug also lowered blood glucose and blood pressure and led to some significant weight loss. The drug also was shown to decrease vascular resistance and albuminuria (N Engl J Med. 2015. 373:2117-2).

Furthermore, an analysis of EMPA-REG OUTCOME presented in November at the American Society of Nephrology meeting in San Diego, showed a profound benefit on the new onset and progression of chronic renal disease in diabetes patients. The importance of these results needs emphasis. Up until recently, the Food and Drug Administration has given a pass to diabetes drugs in regard to cardiovascular endpoints; approval has been based on their primary effect on lowering blood glucose. Some drugs in the past, such as rosiglitazone, actually have shown an increase in mortality in some diabetes patients. At long last, FDA approval for diabetes drugs hinges on acceptable outcomes in cardiovascular endpoints. The addition of a drug that can actually affect cardiovascular mortality and morbidity, the major risk factor of diabetes, provides an important addition to therapy.

The other drug that provides a choice of drugs for the treatment of heart failure is Entresto, a combination of sacubitril, a neprilysin inhibitor, and the angiotensin receptor inhibitor valsartan, approved in July 2015. In PARADIGM-HF, the compound was compared to enalapril in the treatment of patients with class II, III, and IV heart failure who were also receiving beta-blockers. Entresto-treated patients reported a 21.8% incidence of the primary outcome measure, cardiovascular death and hospitalization for heart failure, compared with the enalapril alone incidence of 26.5% (P less than .001) (N Engl J Med. 2014;371:993-1004). Investigators initially excluded 11.4% of the recruited patients from the study who could not tolerate Entresto or enalapril therapy. The drugs were well tolerated without any adverse reactions during therapy. Entresto was more effective than enalapril in regards to the occurrence of heart failure and death from any cause over a 27-month average follow-up.

The observations in this study emphasize how much the mortality of heart failure has decreased over the last decade. Cardiovascular deaths have decreased to roughly 7% per year and rehospitalization occurs in about 8% in the first year. Both drugs provide an important incremental benefit in heart failure patients.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

The possibility that we can define the specific and unique treatment for an individual’s specific disease is the holy grail of therapeutics. Our current therapy is largely defined by randomized clinical trials (RCTs), which provide an average response of therapy in a given disease tested in hundreds or thousands of patients.

RCTs identify the statistical benefit of a particular treatment when compared with a placebo in heterogeneous patients who, at best, are demographically similar but do not truly represent the general population.

Dr. Sidney Goldstein

Although an RCT shows an average statistical benefit, some individuals may have a profound benefit; others in the trial may not benefit at all, and some may do worse than placebo. The reason for the differential response is poorly understood. Therefore, treatment programs based on RCT data by definition are crude and imprecise by design for a variety of conditions, including cancer and cardiovascular diseases.

There has been a call for more personalization and precision in defining and developing predictably successful therapy. It is proposed that precision medicine will lead to optimal targeted individualized treatment based on patients’ genetic profile. This has led oncologists to use genetic profiling of therapy based on cells derived from patient’s tumor. Cancer therapy is in the forefront of genomic analysis of tumor tissue in order to guide specific tumor therapy. Unique DNA gene mutations are now being identified that may explain the genesis, spread, and growth of a tumor. It also provides a potential link between the genetic characteristics of the tumor to specific therapy. As a result, a number of laboratories have developed genetic probes that can mitigate gene expression or overexpression and thereby modify progression of disease.

To some degree, the field of cardiology has found some precision in defining individual therapy for the treatment of a variety of expressions of cardiovascular disease. We have drugs that are aimed at the treatment of hypertension, hypercholesterolemia, heart failure, and vascular thrombogenesis, to name some of the major targets. Just as the oncologists are searching for specific treatments of individual tumors, cardiology is searching for specific targets based on our understanding of the pathophysiologic mechanism leading to the expression and progression of disease. We have been fortunate in a large part to be able to measure pathophysiology and therapy at the bedside.

For some time, investigators have been examining the genetic variants in human tissue in order to understand drug responsiveness in several cardiovascular environments. Single nucleotide polymorphisms (SNP) have been discovered in beta-receptors that may define risk factors for disease and function as modifiers of disease once it has occurred. These factors also have the potential to modify beta-receptor response to adrenergic agonists and antagonists. The understanding of the SNP expression is anticipated to lead to the individualization of drug therapy and define or predict an individual’s response to particular drug therapy. As a result, they may explain the spectrum of clinical response observed in RCTs. Similar observations have been observed with the genetic polymorphism, of renin-angiotensin-aldosterone system and sympathetic systems. The understanding of genetic polymorphism may also provide insight into the expression of disease in particular demographic groups.

So far, the cost of these drugs is huge when applied to just a few individuals who are potential beneficiaries of the therapy. Consequently, patient and society and your insurance company are asked to pay the cost of the drugs to treat just a few patients. Over time, it is possible that these unique genomic characteristics can be applied to larger populations and may spread the costs over a larger number of patients. So far, the potential for this to happen is limited.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

The possibility that we can define the specific and unique treatment for an individual’s specific disease is the holy grail of therapeutics. Our current therapy is largely defined by randomized clinical trials (RCTs), which provide an average response of therapy in a given disease tested in hundreds or thousands of patients.

RCTs identify the statistical benefit of a particular treatment when compared with a placebo in heterogeneous patients who, at best, are demographically similar but do not truly represent the general population.

Dr. Sidney Goldstein

Although an RCT shows an average statistical benefit, some individuals may have a profound benefit; others in the trial may not benefit at all, and some may do worse than placebo. The reason for the differential response is poorly understood. Therefore, treatment programs based on RCT data by definition are crude and imprecise by design for a variety of conditions, including cancer and cardiovascular diseases.

There has been a call for more personalization and precision in defining and developing predictably successful therapy. It is proposed that precision medicine will lead to optimal targeted individualized treatment based on patients’ genetic profile. This has led oncologists to use genetic profiling of therapy based on cells derived from patient’s tumor. Cancer therapy is in the forefront of genomic analysis of tumor tissue in order to guide specific tumor therapy. Unique DNA gene mutations are now being identified that may explain the genesis, spread, and growth of a tumor. It also provides a potential link between the genetic characteristics of the tumor to specific therapy. As a result, a number of laboratories have developed genetic probes that can mitigate gene expression or overexpression and thereby modify progression of disease.

To some degree, the field of cardiology has found some precision in defining individual therapy for the treatment of a variety of expressions of cardiovascular disease. We have drugs that are aimed at the treatment of hypertension, hypercholesterolemia, heart failure, and vascular thrombogenesis, to name some of the major targets. Just as the oncologists are searching for specific treatments of individual tumors, cardiology is searching for specific targets based on our understanding of the pathophysiologic mechanism leading to the expression and progression of disease. We have been fortunate in a large part to be able to measure pathophysiology and therapy at the bedside.

For some time, investigators have been examining the genetic variants in human tissue in order to understand drug responsiveness in several cardiovascular environments. Single nucleotide polymorphisms (SNP) have been discovered in beta-receptors that may define risk factors for disease and function as modifiers of disease once it has occurred. These factors also have the potential to modify beta-receptor response to adrenergic agonists and antagonists. The understanding of the SNP expression is anticipated to lead to the individualization of drug therapy and define or predict an individual’s response to particular drug therapy. As a result, they may explain the spectrum of clinical response observed in RCTs. Similar observations have been observed with the genetic polymorphism, of renin-angiotensin-aldosterone system and sympathetic systems. The understanding of genetic polymorphism may also provide insight into the expression of disease in particular demographic groups.

So far, the cost of these drugs is huge when applied to just a few individuals who are potential beneficiaries of the therapy. Consequently, patient and society and your insurance company are asked to pay the cost of the drugs to treat just a few patients. Over time, it is possible that these unique genomic characteristics can be applied to larger populations and may spread the costs over a larger number of patients. So far, the potential for this to happen is limited.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

The possibility that we can define the specific and unique treatment for an individual’s specific disease is the holy grail of therapeutics. Our current therapy is largely defined by randomized clinical trials (RCTs), which provide an average response of therapy in a given disease tested in hundreds or thousands of patients.

RCTs identify the statistical benefit of a particular treatment when compared with a placebo in heterogeneous patients who, at best, are demographically similar but do not truly represent the general population.

Dr. Sidney Goldstein

Although an RCT shows an average statistical benefit, some individuals may have a profound benefit; others in the trial may not benefit at all, and some may do worse than placebo. The reason for the differential response is poorly understood. Therefore, treatment programs based on RCT data by definition are crude and imprecise by design for a variety of conditions, including cancer and cardiovascular diseases.

There has been a call for more personalization and precision in defining and developing predictably successful therapy. It is proposed that precision medicine will lead to optimal targeted individualized treatment based on patients’ genetic profile. This has led oncologists to use genetic profiling of therapy based on cells derived from patient’s tumor. Cancer therapy is in the forefront of genomic analysis of tumor tissue in order to guide specific tumor therapy. Unique DNA gene mutations are now being identified that may explain the genesis, spread, and growth of a tumor. It also provides a potential link between the genetic characteristics of the tumor to specific therapy. As a result, a number of laboratories have developed genetic probes that can mitigate gene expression or overexpression and thereby modify progression of disease.

To some degree, the field of cardiology has found some precision in defining individual therapy for the treatment of a variety of expressions of cardiovascular disease. We have drugs that are aimed at the treatment of hypertension, hypercholesterolemia, heart failure, and vascular thrombogenesis, to name some of the major targets. Just as the oncologists are searching for specific treatments of individual tumors, cardiology is searching for specific targets based on our understanding of the pathophysiologic mechanism leading to the expression and progression of disease. We have been fortunate in a large part to be able to measure pathophysiology and therapy at the bedside.

For some time, investigators have been examining the genetic variants in human tissue in order to understand drug responsiveness in several cardiovascular environments. Single nucleotide polymorphisms (SNP) have been discovered in beta-receptors that may define risk factors for disease and function as modifiers of disease once it has occurred. These factors also have the potential to modify beta-receptor response to adrenergic agonists and antagonists. The understanding of the SNP expression is anticipated to lead to the individualization of drug therapy and define or predict an individual’s response to particular drug therapy. As a result, they may explain the spectrum of clinical response observed in RCTs. Similar observations have been observed with the genetic polymorphism, of renin-angiotensin-aldosterone system and sympathetic systems. The understanding of genetic polymorphism may also provide insight into the expression of disease in particular demographic groups.

So far, the cost of these drugs is huge when applied to just a few individuals who are potential beneficiaries of the therapy. Consequently, patient and society and your insurance company are asked to pay the cost of the drugs to treat just a few patients. Over time, it is possible that these unique genomic characteristics can be applied to larger populations and may spread the costs over a larger number of patients. So far, the potential for this to happen is limited.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

As I listened to Dr. Jackson T. Wright, one of the investigators of the SPRINT Trial, emphasize the importance of treating systolic blood pressure to the target of 120 mm Hg, I thought about the difficulty in treating blood pressure in the elderly.

Successfully lowering blood pressure even to the current target of 140 mm Hg systolic is one of the most difficult therapeutic tasks that I face. But, to my mind, the worldwide success achieved by hypertension therapy has had the most profound effect on cardiovascular medicine in the last half century. I am no epidemiologist, but the striking decrease in cardiovascular mortality in the United States associated with the introduction of the hypertension therapy is undeniable.

The pharmaceutical companies that developed of these drugs, some of which are still around and some that have merged with other entities, never priced these drugs at the potential benefit of decreasing the cost of hypertension to society. If they had, their price would be so exorbitant that their universal benefit to mankind would never have been seen. They were doing their job and returning significant benefit both to humanity and their investors. They priced the drugs so that we could afford to pay for them. All of these drugs – ACE inhibitors, calcium- and beta-blockers, and diuretics – are now available as generics and as a class have had a lasting and continuing impact on the societal cost and benefit.

Yet somehow, the world has changed. I am not the first to notice it. We now have drugs that can cost thousands of dollars a month and none of us can afford to pay for them. Because we now all share in the cost of drug therapy in one way or another, we all pay the cost. The justification for the high price is not based solely on their development cost, which in many instances were developed decades if not centuries ago, but on the presumed net expense of the untreated disease to society or to the achievement of entrepreneurial profits. Hepatitis C was one of the first in which the cost of new drug therapy was based on the net savings associated with the prevention of the chronic liver disease and its subsequent long-term societal expense. Since I am not a hepatologist, it took me a little leap of faith to accept the potential economic benefit of this therapy, but at least the current data suggest that indeed this therapy works. I remain dubious about the calculations of their societal net benefit cost.

Now move forward. We now have two drugs that can lower cholesterol, potentially to levels beyond our imagination, that are now on the high-expense list. According to recent rumors, evolocumab (Repatha, Amgen) and alirocumab (Praluent, Sanofi/Regeneron) will cost someone $12,000-$14,000 a year to lower serum cholesterol almost to immeasurable levels without any evidence of benefit in decreasing cardiovascular disease. (For those of you with short-term memory deficits, we just tried to pump up HDL cholesterol only to find that when successful, it increased mortality.) Now, if these drugs are successful in preventing the development and progression of atherosclerotic disease, as in the example of hepatitis C, I may change my mind and write the script for it.

Meanwhile, drug prices have escalated as a result of speculation in the pharmaceutical market by Wall Street entrepreneurs who buy up the drug patents that have been available for years like isoproterenol and digitalis, for the sole purpose of a creating a monopoly to inflate the price and return large profits to their investors. When questioned about the 20-fold increase in the cost of isoproterenol, a representative of one of the pharmaceutical companies stated, “that the price was based on many factors, including clinical benefits and the value they bring to the patients, physicians, payers, and society” (New York Times 2015 Oct 4 p. BU1, “Side Effects of Hijacking Drug Prices”). The audacity of drug company executives to presume that they are in a position to make that judgment is outrageous. And yet the U.S. Congress makes it illegal for Medicare and Medicaid to bargain for the best drug prices, while European and Asian pay a fraction of what we pay here.

These ruminations only suggest that madness in the pharmaceutical world is not limited to Wall Street but reaches even the higher levels of government. Get your checkbooks out everyone; the best is yet to come.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

As I listened to Dr. Jackson T. Wright, one of the investigators of the SPRINT Trial, emphasize the importance of treating systolic blood pressure to the target of 120 mm Hg, I thought about the difficulty in treating blood pressure in the elderly.

Successfully lowering blood pressure even to the current target of 140 mm Hg systolic is one of the most difficult therapeutic tasks that I face. But, to my mind, the worldwide success achieved by hypertension therapy has had the most profound effect on cardiovascular medicine in the last half century. I am no epidemiologist, but the striking decrease in cardiovascular mortality in the United States associated with the introduction of the hypertension therapy is undeniable.

The pharmaceutical companies that developed of these drugs, some of which are still around and some that have merged with other entities, never priced these drugs at the potential benefit of decreasing the cost of hypertension to society. If they had, their price would be so exorbitant that their universal benefit to mankind would never have been seen. They were doing their job and returning significant benefit both to humanity and their investors. They priced the drugs so that we could afford to pay for them. All of these drugs – ACE inhibitors, calcium- and beta-blockers, and diuretics – are now available as generics and as a class have had a lasting and continuing impact on the societal cost and benefit.

Yet somehow, the world has changed. I am not the first to notice it. We now have drugs that can cost thousands of dollars a month and none of us can afford to pay for them. Because we now all share in the cost of drug therapy in one way or another, we all pay the cost. The justification for the high price is not based solely on their development cost, which in many instances were developed decades if not centuries ago, but on the presumed net expense of the untreated disease to society or to the achievement of entrepreneurial profits. Hepatitis C was one of the first in which the cost of new drug therapy was based on the net savings associated with the prevention of the chronic liver disease and its subsequent long-term societal expense. Since I am not a hepatologist, it took me a little leap of faith to accept the potential economic benefit of this therapy, but at least the current data suggest that indeed this therapy works. I remain dubious about the calculations of their societal net benefit cost.

Now move forward. We now have two drugs that can lower cholesterol, potentially to levels beyond our imagination, that are now on the high-expense list. According to recent rumors, evolocumab (Repatha, Amgen) and alirocumab (Praluent, Sanofi/Regeneron) will cost someone $12,000-$14,000 a year to lower serum cholesterol almost to immeasurable levels without any evidence of benefit in decreasing cardiovascular disease. (For those of you with short-term memory deficits, we just tried to pump up HDL cholesterol only to find that when successful, it increased mortality.) Now, if these drugs are successful in preventing the development and progression of atherosclerotic disease, as in the example of hepatitis C, I may change my mind and write the script for it.

Meanwhile, drug prices have escalated as a result of speculation in the pharmaceutical market by Wall Street entrepreneurs who buy up the drug patents that have been available for years like isoproterenol and digitalis, for the sole purpose of a creating a monopoly to inflate the price and return large profits to their investors. When questioned about the 20-fold increase in the cost of isoproterenol, a representative of one of the pharmaceutical companies stated, “that the price was based on many factors, including clinical benefits and the value they bring to the patients, physicians, payers, and society” (New York Times 2015 Oct 4 p. BU1, “Side Effects of Hijacking Drug Prices”). The audacity of drug company executives to presume that they are in a position to make that judgment is outrageous. And yet the U.S. Congress makes it illegal for Medicare and Medicaid to bargain for the best drug prices, while European and Asian pay a fraction of what we pay here.

These ruminations only suggest that madness in the pharmaceutical world is not limited to Wall Street but reaches even the higher levels of government. Get your checkbooks out everyone; the best is yet to come.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

As I listened to Dr. Jackson T. Wright, one of the investigators of the SPRINT Trial, emphasize the importance of treating systolic blood pressure to the target of 120 mm Hg, I thought about the difficulty in treating blood pressure in the elderly.

Successfully lowering blood pressure even to the current target of 140 mm Hg systolic is one of the most difficult therapeutic tasks that I face. But, to my mind, the worldwide success achieved by hypertension therapy has had the most profound effect on cardiovascular medicine in the last half century. I am no epidemiologist, but the striking decrease in cardiovascular mortality in the United States associated with the introduction of the hypertension therapy is undeniable.

The pharmaceutical companies that developed of these drugs, some of which are still around and some that have merged with other entities, never priced these drugs at the potential benefit of decreasing the cost of hypertension to society. If they had, their price would be so exorbitant that their universal benefit to mankind would never have been seen. They were doing their job and returning significant benefit both to humanity and their investors. They priced the drugs so that we could afford to pay for them. All of these drugs – ACE inhibitors, calcium- and beta-blockers, and diuretics – are now available as generics and as a class have had a lasting and continuing impact on the societal cost and benefit.

Yet somehow, the world has changed. I am not the first to notice it. We now have drugs that can cost thousands of dollars a month and none of us can afford to pay for them. Because we now all share in the cost of drug therapy in one way or another, we all pay the cost. The justification for the high price is not based solely on their development cost, which in many instances were developed decades if not centuries ago, but on the presumed net expense of the untreated disease to society or to the achievement of entrepreneurial profits. Hepatitis C was one of the first in which the cost of new drug therapy was based on the net savings associated with the prevention of the chronic liver disease and its subsequent long-term societal expense. Since I am not a hepatologist, it took me a little leap of faith to accept the potential economic benefit of this therapy, but at least the current data suggest that indeed this therapy works. I remain dubious about the calculations of their societal net benefit cost.

Now move forward. We now have two drugs that can lower cholesterol, potentially to levels beyond our imagination, that are now on the high-expense list. According to recent rumors, evolocumab (Repatha, Amgen) and alirocumab (Praluent, Sanofi/Regeneron) will cost someone $12,000-$14,000 a year to lower serum cholesterol almost to immeasurable levels without any evidence of benefit in decreasing cardiovascular disease. (For those of you with short-term memory deficits, we just tried to pump up HDL cholesterol only to find that when successful, it increased mortality.) Now, if these drugs are successful in preventing the development and progression of atherosclerotic disease, as in the example of hepatitis C, I may change my mind and write the script for it.

Meanwhile, drug prices have escalated as a result of speculation in the pharmaceutical market by Wall Street entrepreneurs who buy up the drug patents that have been available for years like isoproterenol and digitalis, for the sole purpose of a creating a monopoly to inflate the price and return large profits to their investors. When questioned about the 20-fold increase in the cost of isoproterenol, a representative of one of the pharmaceutical companies stated, “that the price was based on many factors, including clinical benefits and the value they bring to the patients, physicians, payers, and society” (New York Times 2015 Oct 4 p. BU1, “Side Effects of Hijacking Drug Prices”). The audacity of drug company executives to presume that they are in a position to make that judgment is outrageous. And yet the U.S. Congress makes it illegal for Medicare and Medicaid to bargain for the best drug prices, while European and Asian pay a fraction of what we pay here.

These ruminations only suggest that madness in the pharmaceutical world is not limited to Wall Street but reaches even the higher levels of government. Get your checkbooks out everyone; the best is yet to come.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

There has been a spate of recent publications dealing with the lack of implantable cardioverter-defibrillator implantations in the elderly. The most recent indicates that only 8% of patients over age 75 years who have experienced a non–ST-segment elevation myocardial infarction (NSTEMI) or STEMI receive an ICD largely due to the restriction of implantation within 40 days of the incident infarction because of the delayed repair of ventricular function after an MI and the uncertainty of ejection fraction measurements during this period. That article indicates that despite this delay, patients who receive an ICD had an improved survival over the subsequent 2 years, compared with those who did not (JAMA. 2015;313[24]:2433-40). Some of my octogenarian friends might question whether improved survival and the prevention of sudden death is a benefit at that age.

An accompanying editorial suggests that a closer follow-up of these patients is warranted in order to improve the rate of implantation in those patients who are discharged so that they do not “fall through the cracks” and are lost to follow-up (JAMA. 2015:313[24]:2429-30).

Although there has been a tapering off of the explosive use of ICDs in the United States, almost a quarter million devices were implanted between 2010 and 2011 (Heart Rhythm. 2013 Apr;10[4]:e59-65). The U.S. number is roughly four times that of Western Europe. Primary prevention was the reason for implantation in 73.8%, and half of the implantations were in patients over 65; 29% were in the 70-79 age group, and 14% were octogenarians. A history of New York Heart Association class II-IV heart failure was present in 82% and a myocardial infarction in 49%.

There are of course other reasons why the elderly may not receive an ICD. The most frequent are the presence of concomitant diseases like stroke, cancer, and chronic renal disease. However, many elderly do not wish to have their survival tied to a device that they have no control over. Some may view sudden death as an acceptable mortality outcome considering other alternatives. Certainly, adverse lifestyle changes at advanced age may be a reason for the reluctance to choose an ICD.

The application of our new technologies like ICDs, catheter-implanted aortic valves, and mini–left ventricular assist devices have been remarkably successful and have brought lifesaving interventions to thousands of patients. Their relative ease of application has led to a casualness in regard to appropriateness in patients with concomitant diseases, and particularly in the elderly.

The definition of who is elderly has changed dramatically in clinical trials from the mid–20th century when those studies excluded patients over 65. In today’s world, the definition of the elderly has become a slippery slope, as there is no age limit and the inclusion of octogenarians is not unusual. The observation that elderly postinfarction patients with decreased ejection fraction can experience improved survival needs to be evaluated in the light of important considerations of current and expected quality of life in individual patients, as well as their own mortality expectations.

Most of the studies examining implantation rates, extensively analyze the effect of comorbidity and cost benefit of implantation. They rarely deal with how quality of life of the patient and their own mortality expectation impacts on the decision for ICD implantation. Once implanted, removal of the device is often impossible and when possible, as with an ICD, raise important and difficult ethical questions for patient, family, and doctor.

For those of us who are octogenarians and treat octogenarians, these issues are first and foremost in the decision process. The decision to use these devices for the relatively short-term benefit may become an onerous burden for the very elderly whose future quality of life can become abruptly abbreviated by the aging process. Easy exodus from life by sudden death may unfortunately be prolonged by an ICD.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

There has been a spate of recent publications dealing with the lack of implantable cardioverter-defibrillator implantations in the elderly. The most recent indicates that only 8% of patients over age 75 years who have experienced a non–ST-segment elevation myocardial infarction (NSTEMI) or STEMI receive an ICD largely due to the restriction of implantation within 40 days of the incident infarction because of the delayed repair of ventricular function after an MI and the uncertainty of ejection fraction measurements during this period. That article indicates that despite this delay, patients who receive an ICD had an improved survival over the subsequent 2 years, compared with those who did not (JAMA. 2015;313[24]:2433-40). Some of my octogenarian friends might question whether improved survival and the prevention of sudden death is a benefit at that age.

An accompanying editorial suggests that a closer follow-up of these patients is warranted in order to improve the rate of implantation in those patients who are discharged so that they do not “fall through the cracks” and are lost to follow-up (JAMA. 2015:313[24]:2429-30).

Although there has been a tapering off of the explosive use of ICDs in the United States, almost a quarter million devices were implanted between 2010 and 2011 (Heart Rhythm. 2013 Apr;10[4]:e59-65). The U.S. number is roughly four times that of Western Europe. Primary prevention was the reason for implantation in 73.8%, and half of the implantations were in patients over 65; 29% were in the 70-79 age group, and 14% were octogenarians. A history of New York Heart Association class II-IV heart failure was present in 82% and a myocardial infarction in 49%.

There are of course other reasons why the elderly may not receive an ICD. The most frequent are the presence of concomitant diseases like stroke, cancer, and chronic renal disease. However, many elderly do not wish to have their survival tied to a device that they have no control over. Some may view sudden death as an acceptable mortality outcome considering other alternatives. Certainly, adverse lifestyle changes at advanced age may be a reason for the reluctance to choose an ICD.

The application of our new technologies like ICDs, catheter-implanted aortic valves, and mini–left ventricular assist devices have been remarkably successful and have brought lifesaving interventions to thousands of patients. Their relative ease of application has led to a casualness in regard to appropriateness in patients with concomitant diseases, and particularly in the elderly.

The definition of who is elderly has changed dramatically in clinical trials from the mid–20th century when those studies excluded patients over 65. In today’s world, the definition of the elderly has become a slippery slope, as there is no age limit and the inclusion of octogenarians is not unusual. The observation that elderly postinfarction patients with decreased ejection fraction can experience improved survival needs to be evaluated in the light of important considerations of current and expected quality of life in individual patients, as well as their own mortality expectations.

Most of the studies examining implantation rates, extensively analyze the effect of comorbidity and cost benefit of implantation. They rarely deal with how quality of life of the patient and their own mortality expectation impacts on the decision for ICD implantation. Once implanted, removal of the device is often impossible and when possible, as with an ICD, raise important and difficult ethical questions for patient, family, and doctor.

For those of us who are octogenarians and treat octogenarians, these issues are first and foremost in the decision process. The decision to use these devices for the relatively short-term benefit may become an onerous burden for the very elderly whose future quality of life can become abruptly abbreviated by the aging process. Easy exodus from life by sudden death may unfortunately be prolonged by an ICD.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

There has been a spate of recent publications dealing with the lack of implantable cardioverter-defibrillator implantations in the elderly. The most recent indicates that only 8% of patients over age 75 years who have experienced a non–ST-segment elevation myocardial infarction (NSTEMI) or STEMI receive an ICD largely due to the restriction of implantation within 40 days of the incident infarction because of the delayed repair of ventricular function after an MI and the uncertainty of ejection fraction measurements during this period. That article indicates that despite this delay, patients who receive an ICD had an improved survival over the subsequent 2 years, compared with those who did not (JAMA. 2015;313[24]:2433-40). Some of my octogenarian friends might question whether improved survival and the prevention of sudden death is a benefit at that age.

An accompanying editorial suggests that a closer follow-up of these patients is warranted in order to improve the rate of implantation in those patients who are discharged so that they do not “fall through the cracks” and are lost to follow-up (JAMA. 2015:313[24]:2429-30).

Although there has been a tapering off of the explosive use of ICDs in the United States, almost a quarter million devices were implanted between 2010 and 2011 (Heart Rhythm. 2013 Apr;10[4]:e59-65). The U.S. number is roughly four times that of Western Europe. Primary prevention was the reason for implantation in 73.8%, and half of the implantations were in patients over 65; 29% were in the 70-79 age group, and 14% were octogenarians. A history of New York Heart Association class II-IV heart failure was present in 82% and a myocardial infarction in 49%.

There are of course other reasons why the elderly may not receive an ICD. The most frequent are the presence of concomitant diseases like stroke, cancer, and chronic renal disease. However, many elderly do not wish to have their survival tied to a device that they have no control over. Some may view sudden death as an acceptable mortality outcome considering other alternatives. Certainly, adverse lifestyle changes at advanced age may be a reason for the reluctance to choose an ICD.

The application of our new technologies like ICDs, catheter-implanted aortic valves, and mini–left ventricular assist devices have been remarkably successful and have brought lifesaving interventions to thousands of patients. Their relative ease of application has led to a casualness in regard to appropriateness in patients with concomitant diseases, and particularly in the elderly.

The definition of who is elderly has changed dramatically in clinical trials from the mid–20th century when those studies excluded patients over 65. In today’s world, the definition of the elderly has become a slippery slope, as there is no age limit and the inclusion of octogenarians is not unusual. The observation that elderly postinfarction patients with decreased ejection fraction can experience improved survival needs to be evaluated in the light of important considerations of current and expected quality of life in individual patients, as well as their own mortality expectations.

Most of the studies examining implantation rates, extensively analyze the effect of comorbidity and cost benefit of implantation. They rarely deal with how quality of life of the patient and their own mortality expectation impacts on the decision for ICD implantation. Once implanted, removal of the device is often impossible and when possible, as with an ICD, raise important and difficult ethical questions for patient, family, and doctor.

For those of us who are octogenarians and treat octogenarians, these issues are first and foremost in the decision process. The decision to use these devices for the relatively short-term benefit may become an onerous burden for the very elderly whose future quality of life can become abruptly abbreviated by the aging process. Easy exodus from life by sudden death may unfortunately be prolonged by an ICD.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

The recent endorsements by the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee of the new genetically manufactured, subcutaneously administered cholesterol-lowering agents alirocumab (Sanofi-Regeneron) and evolocumab (Pfizer) have sent a jolt through the world of cholesterol therapy. Proposed for the treatment of patients with high-risk cardiovascular disease and homozygous familial hypercholesterolemia (HoFH), the decisions suggest that the committee has developed a severe case of scientific amnesia.

A case can be made for the approval for the very-high-risk and untreatable patients with HoFH, but the decision to treat millions of Americans based on the paucity of clinical data available would be disturbing, if not irresponsible.

It is clear that these proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors provide a powerful therapy for reducing LDL cholesterol, with a reported decrease of about 60% after only 12 or 52 weeks of treatment. Based on four small studies lasting 10-12 weeks and without any clinical outcome data, the committee recommended approving evolocumab for lifetime therapy without anything to support its clinical effectiveness or safety.

Dr. Robert J. Smith, who chaired the advisory committee meeting, faced with approving the drug or delaying a decision until a randomized clinical trial can be completed said, “I am unwilling to subject patients to the wait.” A publication of the American College of Cardiology suggested that these two monoclonal antibody drugs could replace generic statins in 70 million Americans at an estimated cost of $7,000-$12,000 a year. Talk about breaking the bank.

Only recently, we decided that the appropriate statin therapy for cholesterol control should use the dosing from the original clinical trials rather than chasing LDL levels to the lowest level possible. We now have a class of drugs that clearly can lower the cholesterol to a level never seen before, and we are about to discard that therapeutic advice.

We have experience in chasing blood levels with uncertain outcomes. Reducing blood sugar to a very low hemoglobin A_1c level led to adverse clinical events and increased mortality in type 2 diabetes. Raising HDL with the cholesterol ester transfer protein (CETP) inhibitor torcetrapib in a study of 15,000 patients in an outcome trial carried out over a number of years led to increased blood pressure and mortality by 58%, which was associated with a 25% decrease in LDL cholesterol and a 72% increase in HDL, both effects presumed to be remarkably beneficial (N. Engl. J. Med. 2007;357:2109-22).

It is quite possible that these new agents can further decrease coronary vascular mortality. A healthy controversy has raged for some time in regard to the “LDL hypothesis,” compared with therapy based upon the clinical trial outcome. The recent IMPROVE-IT report (N. Engl. J. Med. 2015;372:2387-97) provides some data to support the LDL hypothesis. In that study, the addition of 10 mg of ezetimibe to 40 mg of simvastatin in 18,144 patients followed for up to 6 years resulted in a 2% decrease in mortality associated with a 15.8-mg decrease in serum LDL.

Would it not be prudent to have similar data with the new drug on the street? If it is as potent as it appears to be, a trial of much shorter duration might demonstrate its potency and safety before it is offered to 70 million Americans. The FDA has been reluctant to use surrogate endpoints for approving drugs, but its position has not always been consistent. For some time the FDA has, on occasion, approved drugs that can lower cholesterol with limited outcome data as it did with ezetimibe. However, the decision in regard to the PCSK9 inhibitors will have a much larger impact on care than an add-on drug like ezetimibe. Let’s hope that the FDA shows better judgment than its advisory committee.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

The recent endorsements by the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee of the new genetically manufactured, subcutaneously administered cholesterol-lowering agents alirocumab (Sanofi-Regeneron) and evolocumab (Pfizer) have sent a jolt through the world of cholesterol therapy. Proposed for the treatment of patients with high-risk cardiovascular disease and homozygous familial hypercholesterolemia (HoFH), the decisions suggest that the committee has developed a severe case of scientific amnesia.

A case can be made for the approval for the very-high-risk and untreatable patients with HoFH, but the decision to treat millions of Americans based on the paucity of clinical data available would be disturbing, if not irresponsible.

It is clear that these proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors provide a powerful therapy for reducing LDL cholesterol, with a reported decrease of about 60% after only 12 or 52 weeks of treatment. Based on four small studies lasting 10-12 weeks and without any clinical outcome data, the committee recommended approving evolocumab for lifetime therapy without anything to support its clinical effectiveness or safety.

Dr. Robert J. Smith, who chaired the advisory committee meeting, faced with approving the drug or delaying a decision until a randomized clinical trial can be completed said, “I am unwilling to subject patients to the wait.” A publication of the American College of Cardiology suggested that these two monoclonal antibody drugs could replace generic statins in 70 million Americans at an estimated cost of $7,000-$12,000 a year. Talk about breaking the bank.

Only recently, we decided that the appropriate statin therapy for cholesterol control should use the dosing from the original clinical trials rather than chasing LDL levels to the lowest level possible. We now have a class of drugs that clearly can lower the cholesterol to a level never seen before, and we are about to discard that therapeutic advice.

We have experience in chasing blood levels with uncertain outcomes. Reducing blood sugar to a very low hemoglobin A_1c level led to adverse clinical events and increased mortality in type 2 diabetes. Raising HDL with the cholesterol ester transfer protein (CETP) inhibitor torcetrapib in a study of 15,000 patients in an outcome trial carried out over a number of years led to increased blood pressure and mortality by 58%, which was associated with a 25% decrease in LDL cholesterol and a 72% increase in HDL, both effects presumed to be remarkably beneficial (N. Engl. J. Med. 2007;357:2109-22).

It is quite possible that these new agents can further decrease coronary vascular mortality. A healthy controversy has raged for some time in regard to the “LDL hypothesis,” compared with therapy based upon the clinical trial outcome. The recent IMPROVE-IT report (N. Engl. J. Med. 2015;372:2387-97) provides some data to support the LDL hypothesis. In that study, the addition of 10 mg of ezetimibe to 40 mg of simvastatin in 18,144 patients followed for up to 6 years resulted in a 2% decrease in mortality associated with a 15.8-mg decrease in serum LDL.

Would it not be prudent to have similar data with the new drug on the street? If it is as potent as it appears to be, a trial of much shorter duration might demonstrate its potency and safety before it is offered to 70 million Americans. The FDA has been reluctant to use surrogate endpoints for approving drugs, but its position has not always been consistent. For some time the FDA has, on occasion, approved drugs that can lower cholesterol with limited outcome data as it did with ezetimibe. However, the decision in regard to the PCSK9 inhibitors will have a much larger impact on care than an add-on drug like ezetimibe. Let’s hope that the FDA shows better judgment than its advisory committee.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

The recent endorsements by the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee of the new genetically manufactured, subcutaneously administered cholesterol-lowering agents alirocumab (Sanofi-Regeneron) and evolocumab (Pfizer) have sent a jolt through the world of cholesterol therapy. Proposed for the treatment of patients with high-risk cardiovascular disease and homozygous familial hypercholesterolemia (HoFH), the decisions suggest that the committee has developed a severe case of scientific amnesia.

A case can be made for the approval for the very-high-risk and untreatable patients with HoFH, but the decision to treat millions of Americans based on the paucity of clinical data available would be disturbing, if not irresponsible.

It is clear that these proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors provide a powerful therapy for reducing LDL cholesterol, with a reported decrease of about 60% after only 12 or 52 weeks of treatment. Based on four small studies lasting 10-12 weeks and without any clinical outcome data, the committee recommended approving evolocumab for lifetime therapy without anything to support its clinical effectiveness or safety.

Dr. Robert J. Smith, who chaired the advisory committee meeting, faced with approving the drug or delaying a decision until a randomized clinical trial can be completed said, “I am unwilling to subject patients to the wait.” A publication of the American College of Cardiology suggested that these two monoclonal antibody drugs could replace generic statins in 70 million Americans at an estimated cost of $7,000-$12,000 a year. Talk about breaking the bank.

Only recently, we decided that the appropriate statin therapy for cholesterol control should use the dosing from the original clinical trials rather than chasing LDL levels to the lowest level possible. We now have a class of drugs that clearly can lower the cholesterol to a level never seen before, and we are about to discard that therapeutic advice.

We have experience in chasing blood levels with uncertain outcomes. Reducing blood sugar to a very low hemoglobin A_1c level led to adverse clinical events and increased mortality in type 2 diabetes. Raising HDL with the cholesterol ester transfer protein (CETP) inhibitor torcetrapib in a study of 15,000 patients in an outcome trial carried out over a number of years led to increased blood pressure and mortality by 58%, which was associated with a 25% decrease in LDL cholesterol and a 72% increase in HDL, both effects presumed to be remarkably beneficial (N. Engl. J. Med. 2007;357:2109-22).

It is quite possible that these new agents can further decrease coronary vascular mortality. A healthy controversy has raged for some time in regard to the “LDL hypothesis,” compared with therapy based upon the clinical trial outcome. The recent IMPROVE-IT report (N. Engl. J. Med. 2015;372:2387-97) provides some data to support the LDL hypothesis. In that study, the addition of 10 mg of ezetimibe to 40 mg of simvastatin in 18,144 patients followed for up to 6 years resulted in a 2% decrease in mortality associated with a 15.8-mg decrease in serum LDL.

Would it not be prudent to have similar data with the new drug on the street? If it is as potent as it appears to be, a trial of much shorter duration might demonstrate its potency and safety before it is offered to 70 million Americans. The FDA has been reluctant to use surrogate endpoints for approving drugs, but its position has not always been consistent. For some time the FDA has, on occasion, approved drugs that can lower cholesterol with limited outcome data as it did with ezetimibe. However, the decision in regard to the PCSK9 inhibitors will have a much larger impact on care than an add-on drug like ezetimibe. Let’s hope that the FDA shows better judgment than its advisory committee.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.