Upper GI Tract

Patients with severe diabetes but only mild obesity see a dramatic benefit after gastric bypass surgery, a new study has found, with 88% experiencing durable disease remission within 6 months, along with major reductions in 10-year cardiovascular risk.

No mortality, major surgical complications, excessive weight loss, or malnutrition was seen among the 66 patients in the study, all of whom underwent laparoscopic Roux-en-Y gastric bypass (RYGB) surgery, according to the findings published in the July issue of Diabetes Care (2012;35:1420-8) and presented at the annual scientific sessions of the American Diabetes Association in Philadelphia.

Bariatric surgery is currently recommended by the National Institutes of Health only for people with a body mass index (BMI) of 40 kg/m² or higher, or above 35 for people with comorbidities such as severe diabetes. Very obese patients with diabetes have seen dramatic reductions in disease activity after RYGB surgery, with an estimated 80%-85% experiencing durable remission. There is increasing evidence that the procedure triggers hormonal and metabolic antidiabetes responses independent of weight loss (Annu. Rev. Med. 2010;61:393-411; Int. J. Obes. 2009;33:S33-S40; Endocrinology 2009;150:2518-25).

People with mild obesity and diabetes constitute a larger group than the very obese, yet they do not currently qualify for bariatric surgery.

Dr. Ricardo V. Cohen of Oswaldo Cruz Hospital and Marcia Maria Braido Hospital, both in São Paulo, Brazil, and his colleagues sought to investigate whether people with a lower BMI and poorly controlled diabetes also would see significant benefit. More than one-fourth of people in the United States with diabetes have class I obesity, or a BMI of 30-35 (Int. J. Clin. Pract. 2007;61:737-47).

For their research, Dr. Cohen and his colleagues recruited 40 men and 26 women. All were white and ranged in age from 31 to 63 years, and had a BMI of 30.0-34.9 and diabetes lasting 7 years or more at the time of surgery. The mean HbA_1c level was 9.7% at the time of surgery, despite the use of insulin and/or oral diabetes medications (n = 7 on insulin). Follow-up on the cohort was 100%, for a median 5 years.

Within 26 weeks after surgery, 88% of patients were able to discontinue their diabetes medications and maintain an HbA_1c level of less than 6.5% without resuming diabetes medications in the follow-up period.

Improvement without remission was seen in 11% of patients, who were able to withdraw insulin and/or reduce dosages of oral medications between 3 and 14 weeks after surgery. One patient showed no improvement in glycemic control, but was able to withdraw insulin and achieve diabetes control with oral medications 7 months post surgery.

Mean HbA_1c for the entire cohort fell progressively throughout the study, from 9.7% to 5.9% (P less than .001). Fasting plasma glucose (FPG) fell from 156 mg/dL to 97 mg/dL (P less than .001). Most of these changes occurred within the first 6 months.

All patients saw progressive reductions in waist circumference and total body weight, although the magnitude of weight loss was not seen as corresponding with decreases in either FPG or HbA_1c until after 5 years post surgery, when the investigators saw significant correlations between weight loss and decrease in FPG. No correlations were seen between weight loss and decrease in HbA_1c. Also, while the ratio of change in C-peptide to change in glucose increased significantly in the postoperative period, there was no correlation seen between the magnitude of the increase and weight lost. All these findings suggest that the surgery induces mechanisms of antidiabetes action independent of weight loss.

The predicted 10-year risk of cardiovascular disease fell after surgery in the cohort, with a 71% decrease in coronary heart disease (CHD, P = .001), 84% decrease in fatal CHD (P = .001), 50% decrease in stroke (P = .01), and 57% decrease in fatal stroke (P = .009). Hypertension and dyslipidemia were also seen to have improved, with hypertension resolving in 15 of the 26 (58%) patients who had it at baseline, hypercholesterolemia resolving in 21 of 33 (64%) patients, and hypertriglyceridemia resolving in 18 of 31 (58%), in the follow-up period.

Importantly, none of the subjects lost excessive weight or showed evidence of malnutrition. The lowest BMI observed in the follow-up period was 23.6.

The findings, Dr. Cohen and his colleagues wrote in their analysis, have broad implications for health policy, as they "indicate that RYGB is a safe, effective procedure to ameliorate type 2 diabetes and associated comorbidities, thereby reducing predicted cardiovascular disease risk, in patients with a BMI of 30–35 kg/m²."

While randomized controlled trial data are required to confirm that the procedure can be recommended in these patients, the investigators wrote, "our favorable findings from a relatively large, long-term study help justify such trials to clarify whether standard indications for RYGB should be broadened and whether this operation might be viewed primarily as ‘metabolic,’ rather than ‘bariatric,’ surgery."

Dr. Cohen and colleagues’ study was funded by the Municipal Health Authority and Marcia Maria Braido Hospital in São Paulo, Brazil. Dr. Cohen disclosed that he received previous study funding from Covidien, and one of his coauthors, Dr. David E. Cummings of the University of Washington, Seattle, disclosed receiving past funding from Ethicon Endo-Surgery. The other authors said they had no relevant financial disclosures.

Patients with severe diabetes but only mild obesity see a dramatic benefit after gastric bypass surgery, a new study has found, with 88% experiencing durable disease remission within 6 months, along with major reductions in 10-year cardiovascular risk.

No mortality, major surgical complications, excessive weight loss, or malnutrition was seen among the 66 patients in the study, all of whom underwent laparoscopic Roux-en-Y gastric bypass (RYGB) surgery, according to the findings published in the July issue of Diabetes Care (2012;35:1420-8) and presented at the annual scientific sessions of the American Diabetes Association in Philadelphia.

Bariatric surgery is currently recommended by the National Institutes of Health only for people with a body mass index (BMI) of 40 kg/m² or higher, or above 35 for people with comorbidities such as severe diabetes. Very obese patients with diabetes have seen dramatic reductions in disease activity after RYGB surgery, with an estimated 80%-85% experiencing durable remission. There is increasing evidence that the procedure triggers hormonal and metabolic antidiabetes responses independent of weight loss (Annu. Rev. Med. 2010;61:393-411; Int. J. Obes. 2009;33:S33-S40; Endocrinology 2009;150:2518-25).

People with mild obesity and diabetes constitute a larger group than the very obese, yet they do not currently qualify for bariatric surgery.

Dr. Ricardo V. Cohen of Oswaldo Cruz Hospital and Marcia Maria Braido Hospital, both in São Paulo, Brazil, and his colleagues sought to investigate whether people with a lower BMI and poorly controlled diabetes also would see significant benefit. More than one-fourth of people in the United States with diabetes have class I obesity, or a BMI of 30-35 (Int. J. Clin. Pract. 2007;61:737-47).

For their research, Dr. Cohen and his colleagues recruited 40 men and 26 women. All were white and ranged in age from 31 to 63 years, and had a BMI of 30.0-34.9 and diabetes lasting 7 years or more at the time of surgery. The mean HbA_1c level was 9.7% at the time of surgery, despite the use of insulin and/or oral diabetes medications (n = 7 on insulin). Follow-up on the cohort was 100%, for a median 5 years.

Within 26 weeks after surgery, 88% of patients were able to discontinue their diabetes medications and maintain an HbA_1c level of less than 6.5% without resuming diabetes medications in the follow-up period.

Improvement without remission was seen in 11% of patients, who were able to withdraw insulin and/or reduce dosages of oral medications between 3 and 14 weeks after surgery. One patient showed no improvement in glycemic control, but was able to withdraw insulin and achieve diabetes control with oral medications 7 months post surgery.

Mean HbA_1c for the entire cohort fell progressively throughout the study, from 9.7% to 5.9% (P less than .001). Fasting plasma glucose (FPG) fell from 156 mg/dL to 97 mg/dL (P less than .001). Most of these changes occurred within the first 6 months.

All patients saw progressive reductions in waist circumference and total body weight, although the magnitude of weight loss was not seen as corresponding with decreases in either FPG or HbA_1c until after 5 years post surgery, when the investigators saw significant correlations between weight loss and decrease in FPG. No correlations were seen between weight loss and decrease in HbA_1c. Also, while the ratio of change in C-peptide to change in glucose increased significantly in the postoperative period, there was no correlation seen between the magnitude of the increase and weight lost. All these findings suggest that the surgery induces mechanisms of antidiabetes action independent of weight loss.

The predicted 10-year risk of cardiovascular disease fell after surgery in the cohort, with a 71% decrease in coronary heart disease (CHD, P = .001), 84% decrease in fatal CHD (P = .001), 50% decrease in stroke (P = .01), and 57% decrease in fatal stroke (P = .009). Hypertension and dyslipidemia were also seen to have improved, with hypertension resolving in 15 of the 26 (58%) patients who had it at baseline, hypercholesterolemia resolving in 21 of 33 (64%) patients, and hypertriglyceridemia resolving in 18 of 31 (58%), in the follow-up period.

Importantly, none of the subjects lost excessive weight or showed evidence of malnutrition. The lowest BMI observed in the follow-up period was 23.6.

The findings, Dr. Cohen and his colleagues wrote in their analysis, have broad implications for health policy, as they "indicate that RYGB is a safe, effective procedure to ameliorate type 2 diabetes and associated comorbidities, thereby reducing predicted cardiovascular disease risk, in patients with a BMI of 30–35 kg/m²."

While randomized controlled trial data are required to confirm that the procedure can be recommended in these patients, the investigators wrote, "our favorable findings from a relatively large, long-term study help justify such trials to clarify whether standard indications for RYGB should be broadened and whether this operation might be viewed primarily as ‘metabolic,’ rather than ‘bariatric,’ surgery."

Dr. Cohen and colleagues’ study was funded by the Municipal Health Authority and Marcia Maria Braido Hospital in São Paulo, Brazil. Dr. Cohen disclosed that he received previous study funding from Covidien, and one of his coauthors, Dr. David E. Cummings of the University of Washington, Seattle, disclosed receiving past funding from Ethicon Endo-Surgery. The other authors said they had no relevant financial disclosures.

Patients with severe diabetes but only mild obesity see a dramatic benefit after gastric bypass surgery, a new study has found, with 88% experiencing durable disease remission within 6 months, along with major reductions in 10-year cardiovascular risk.

No mortality, major surgical complications, excessive weight loss, or malnutrition was seen among the 66 patients in the study, all of whom underwent laparoscopic Roux-en-Y gastric bypass (RYGB) surgery, according to the findings published in the July issue of Diabetes Care (2012;35:1420-8) and presented at the annual scientific sessions of the American Diabetes Association in Philadelphia.

Bariatric surgery is currently recommended by the National Institutes of Health only for people with a body mass index (BMI) of 40 kg/m² or higher, or above 35 for people with comorbidities such as severe diabetes. Very obese patients with diabetes have seen dramatic reductions in disease activity after RYGB surgery, with an estimated 80%-85% experiencing durable remission. There is increasing evidence that the procedure triggers hormonal and metabolic antidiabetes responses independent of weight loss (Annu. Rev. Med. 2010;61:393-411; Int. J. Obes. 2009;33:S33-S40; Endocrinology 2009;150:2518-25).

People with mild obesity and diabetes constitute a larger group than the very obese, yet they do not currently qualify for bariatric surgery.

Dr. Ricardo V. Cohen of Oswaldo Cruz Hospital and Marcia Maria Braido Hospital, both in São Paulo, Brazil, and his colleagues sought to investigate whether people with a lower BMI and poorly controlled diabetes also would see significant benefit. More than one-fourth of people in the United States with diabetes have class I obesity, or a BMI of 30-35 (Int. J. Clin. Pract. 2007;61:737-47).

For their research, Dr. Cohen and his colleagues recruited 40 men and 26 women. All were white and ranged in age from 31 to 63 years, and had a BMI of 30.0-34.9 and diabetes lasting 7 years or more at the time of surgery. The mean HbA_1c level was 9.7% at the time of surgery, despite the use of insulin and/or oral diabetes medications (n = 7 on insulin). Follow-up on the cohort was 100%, for a median 5 years.

Within 26 weeks after surgery, 88% of patients were able to discontinue their diabetes medications and maintain an HbA_1c level of less than 6.5% without resuming diabetes medications in the follow-up period.

Improvement without remission was seen in 11% of patients, who were able to withdraw insulin and/or reduce dosages of oral medications between 3 and 14 weeks after surgery. One patient showed no improvement in glycemic control, but was able to withdraw insulin and achieve diabetes control with oral medications 7 months post surgery.

Mean HbA_1c for the entire cohort fell progressively throughout the study, from 9.7% to 5.9% (P less than .001). Fasting plasma glucose (FPG) fell from 156 mg/dL to 97 mg/dL (P less than .001). Most of these changes occurred within the first 6 months.

All patients saw progressive reductions in waist circumference and total body weight, although the magnitude of weight loss was not seen as corresponding with decreases in either FPG or HbA_1c until after 5 years post surgery, when the investigators saw significant correlations between weight loss and decrease in FPG. No correlations were seen between weight loss and decrease in HbA_1c. Also, while the ratio of change in C-peptide to change in glucose increased significantly in the postoperative period, there was no correlation seen between the magnitude of the increase and weight lost. All these findings suggest that the surgery induces mechanisms of antidiabetes action independent of weight loss.

The predicted 10-year risk of cardiovascular disease fell after surgery in the cohort, with a 71% decrease in coronary heart disease (CHD, P = .001), 84% decrease in fatal CHD (P = .001), 50% decrease in stroke (P = .01), and 57% decrease in fatal stroke (P = .009). Hypertension and dyslipidemia were also seen to have improved, with hypertension resolving in 15 of the 26 (58%) patients who had it at baseline, hypercholesterolemia resolving in 21 of 33 (64%) patients, and hypertriglyceridemia resolving in 18 of 31 (58%), in the follow-up period.

Importantly, none of the subjects lost excessive weight or showed evidence of malnutrition. The lowest BMI observed in the follow-up period was 23.6.

The findings, Dr. Cohen and his colleagues wrote in their analysis, have broad implications for health policy, as they "indicate that RYGB is a safe, effective procedure to ameliorate type 2 diabetes and associated comorbidities, thereby reducing predicted cardiovascular disease risk, in patients with a BMI of 30–35 kg/m²."

While randomized controlled trial data are required to confirm that the procedure can be recommended in these patients, the investigators wrote, "our favorable findings from a relatively large, long-term study help justify such trials to clarify whether standard indications for RYGB should be broadened and whether this operation might be viewed primarily as ‘metabolic,’ rather than ‘bariatric,’ surgery."

Dr. Cohen and colleagues’ study was funded by the Municipal Health Authority and Marcia Maria Braido Hospital in São Paulo, Brazil. Dr. Cohen disclosed that he received previous study funding from Covidien, and one of his coauthors, Dr. David E. Cummings of the University of Washington, Seattle, disclosed receiving past funding from Ethicon Endo-Surgery. The other authors said they had no relevant financial disclosures.

The risk of major bleeding events in Italians taking low-dose aspirin was more than 50% higher than in those not on the regimen in a large population-based cohort study.

However, those with diabetes had showed no increase in bleeding risk.

"Weighing the benefits of aspirin therapy against the potential harms is of particular relevance in the primary prevention setting, in which benefits seem to be lower than expected based on results in high risk populations," concluded Giorgia De Berardis of the department of clinical pharmacology and epidemiology, Consorzio Mario Negri Sud, S. Maria Imbaro, Italy, and her associates. The study was published online on June 6 (JAMA 2012;307:2286-94).

Although low-dose aspirin was associated with an increased risk of major bleeding in people with hypertension and most other subgroups they identified, it was not independently associated with such a risk in people with diabetes, a finding that indicates that "diabetes might represent a different population in terms of both expected benefits and risks associated with antiplatelet therapy," they wrote.

In the study, the investigators used administrative data on people living in 12 local health authorities in Puglia, Italy, which is in the southeastern part of the country, linking data from hospital discharge records, prescription databases (including information on aspirin, which in Italy is prescribed for CV prevention), and the civil registry. They compared hospitalizations for major gastrointestinal bleeding or cerebral hemorrhage among 186,425 users of low-dose aspirin (300 mg or less) during 2003-2008, to matched controls who had never used aspirin. A little over half were women; the mean age was about 69 years.

Over a median follow-up of almost 6 years, 5.58 hemorrhagic events/1,000 person-years occurred in persons on aspirin, compared with 3.60 events/1,000 person-years in those who had never used aspirin, for an increased risk of 55%. Among those on aspirin, the risk of GI bleeding was increased by 55% and the risk of intracranial bleed was increased by 54%, compared with those who had never used aspirin.

Among those on aspirin, the risk of bleeding was increased in most of the subgroups evaluated, and was "particularly high" among those younger than age 50 years(an incidence rate ratio of 1.93 – about a threefold greater risk when compared with people under 50 years who were not on aspirin). It was also increased in aspirin users who had not been treated for hypertension. They pointed out that this increased risk was seen in most of the subgroups they evaluated, except for patients with diabetes and those who had previously been admitted to the hospital for GI or CV problems, which they said could be "partially" attributed to the use of proton pump inhibitors (PPIs).

Those with diabetes who were not taking aspirin had a 59% increased risk for GI bleeding and a 64% increase risk for intracranial bleeding. But among those with diabetes who were on aspirin, the risk of bleeding was only slightly elevated. "Our study shows, for the first time, to our knowledge, that aspirin therapy only marginally increases the risk of bleeding in individuals with diabetes," the authors wrote, adding that these results "can represent indirect evidence that the efficacy of aspirin in suppressing platelet function is reduced in this population."

A notable finding, they said, was that the use of statins was associated with a significant reduction of gastrointestinal bleeding (35%) and intracranial bleeding (31%).

The authors said that the incidence of major bleeding events associated with aspirin identified in their study was "much higher" than reported in randomized prospective studies. The 55% increase in the relative risk of major bleeding, over no aspirin, "translates to 2 excess cases for 1,000 patients treated per year," they said. "In other words, the excess number of major bleeding events associated with the use of aspirin is of the same magnitude of the number of major cardiovascular events avoided in the primary prevention setting for individuals with a 10-year risk of between 10% and 20%."

Limitations of their study include the not being able to adjust for all potential factors that can affect bleeding, including over-the-counter aspirin use, although in Italy, low-dose aspirin for CV prevention in high-risk individuals is available by prescription and is fully covered.

Four of the seven authors, including the lead author, reported no disclosures. One author reported receiving a research grant from Bristol-Myers Squibb, another reported receiving a research grant from Bayer, and another reported receiving a research grant and lecture fees, including service on speakers bureaus from Bayer.

The risk of major bleeding events in Italians taking low-dose aspirin was more than 50% higher than in those not on the regimen in a large population-based cohort study.

However, those with diabetes had showed no increase in bleeding risk.

"Weighing the benefits of aspirin therapy against the potential harms is of particular relevance in the primary prevention setting, in which benefits seem to be lower than expected based on results in high risk populations," concluded Giorgia De Berardis of the department of clinical pharmacology and epidemiology, Consorzio Mario Negri Sud, S. Maria Imbaro, Italy, and her associates. The study was published online on June 6 (JAMA 2012;307:2286-94).

Although low-dose aspirin was associated with an increased risk of major bleeding in people with hypertension and most other subgroups they identified, it was not independently associated with such a risk in people with diabetes, a finding that indicates that "diabetes might represent a different population in terms of both expected benefits and risks associated with antiplatelet therapy," they wrote.

In the study, the investigators used administrative data on people living in 12 local health authorities in Puglia, Italy, which is in the southeastern part of the country, linking data from hospital discharge records, prescription databases (including information on aspirin, which in Italy is prescribed for CV prevention), and the civil registry. They compared hospitalizations for major gastrointestinal bleeding or cerebral hemorrhage among 186,425 users of low-dose aspirin (300 mg or less) during 2003-2008, to matched controls who had never used aspirin. A little over half were women; the mean age was about 69 years.

Over a median follow-up of almost 6 years, 5.58 hemorrhagic events/1,000 person-years occurred in persons on aspirin, compared with 3.60 events/1,000 person-years in those who had never used aspirin, for an increased risk of 55%. Among those on aspirin, the risk of GI bleeding was increased by 55% and the risk of intracranial bleed was increased by 54%, compared with those who had never used aspirin.

Among those on aspirin, the risk of bleeding was increased in most of the subgroups evaluated, and was "particularly high" among those younger than age 50 years(an incidence rate ratio of 1.93 – about a threefold greater risk when compared with people under 50 years who were not on aspirin). It was also increased in aspirin users who had not been treated for hypertension. They pointed out that this increased risk was seen in most of the subgroups they evaluated, except for patients with diabetes and those who had previously been admitted to the hospital for GI or CV problems, which they said could be "partially" attributed to the use of proton pump inhibitors (PPIs).

Those with diabetes who were not taking aspirin had a 59% increased risk for GI bleeding and a 64% increase risk for intracranial bleeding. But among those with diabetes who were on aspirin, the risk of bleeding was only slightly elevated. "Our study shows, for the first time, to our knowledge, that aspirin therapy only marginally increases the risk of bleeding in individuals with diabetes," the authors wrote, adding that these results "can represent indirect evidence that the efficacy of aspirin in suppressing platelet function is reduced in this population."

A notable finding, they said, was that the use of statins was associated with a significant reduction of gastrointestinal bleeding (35%) and intracranial bleeding (31%).

The authors said that the incidence of major bleeding events associated with aspirin identified in their study was "much higher" than reported in randomized prospective studies. The 55% increase in the relative risk of major bleeding, over no aspirin, "translates to 2 excess cases for 1,000 patients treated per year," they said. "In other words, the excess number of major bleeding events associated with the use of aspirin is of the same magnitude of the number of major cardiovascular events avoided in the primary prevention setting for individuals with a 10-year risk of between 10% and 20%."

Limitations of their study include the not being able to adjust for all potential factors that can affect bleeding, including over-the-counter aspirin use, although in Italy, low-dose aspirin for CV prevention in high-risk individuals is available by prescription and is fully covered.

Four of the seven authors, including the lead author, reported no disclosures. One author reported receiving a research grant from Bristol-Myers Squibb, another reported receiving a research grant from Bayer, and another reported receiving a research grant and lecture fees, including service on speakers bureaus from Bayer.

The risk of major bleeding events in Italians taking low-dose aspirin was more than 50% higher than in those not on the regimen in a large population-based cohort study.

However, those with diabetes had showed no increase in bleeding risk.

"Weighing the benefits of aspirin therapy against the potential harms is of particular relevance in the primary prevention setting, in which benefits seem to be lower than expected based on results in high risk populations," concluded Giorgia De Berardis of the department of clinical pharmacology and epidemiology, Consorzio Mario Negri Sud, S. Maria Imbaro, Italy, and her associates. The study was published online on June 6 (JAMA 2012;307:2286-94).

Although low-dose aspirin was associated with an increased risk of major bleeding in people with hypertension and most other subgroups they identified, it was not independently associated with such a risk in people with diabetes, a finding that indicates that "diabetes might represent a different population in terms of both expected benefits and risks associated with antiplatelet therapy," they wrote.

In the study, the investigators used administrative data on people living in 12 local health authorities in Puglia, Italy, which is in the southeastern part of the country, linking data from hospital discharge records, prescription databases (including information on aspirin, which in Italy is prescribed for CV prevention), and the civil registry. They compared hospitalizations for major gastrointestinal bleeding or cerebral hemorrhage among 186,425 users of low-dose aspirin (300 mg or less) during 2003-2008, to matched controls who had never used aspirin. A little over half were women; the mean age was about 69 years.

Over a median follow-up of almost 6 years, 5.58 hemorrhagic events/1,000 person-years occurred in persons on aspirin, compared with 3.60 events/1,000 person-years in those who had never used aspirin, for an increased risk of 55%. Among those on aspirin, the risk of GI bleeding was increased by 55% and the risk of intracranial bleed was increased by 54%, compared with those who had never used aspirin.

Among those on aspirin, the risk of bleeding was increased in most of the subgroups evaluated, and was "particularly high" among those younger than age 50 years(an incidence rate ratio of 1.93 – about a threefold greater risk when compared with people under 50 years who were not on aspirin). It was also increased in aspirin users who had not been treated for hypertension. They pointed out that this increased risk was seen in most of the subgroups they evaluated, except for patients with diabetes and those who had previously been admitted to the hospital for GI or CV problems, which they said could be "partially" attributed to the use of proton pump inhibitors (PPIs).

Those with diabetes who were not taking aspirin had a 59% increased risk for GI bleeding and a 64% increase risk for intracranial bleeding. But among those with diabetes who were on aspirin, the risk of bleeding was only slightly elevated. "Our study shows, for the first time, to our knowledge, that aspirin therapy only marginally increases the risk of bleeding in individuals with diabetes," the authors wrote, adding that these results "can represent indirect evidence that the efficacy of aspirin in suppressing platelet function is reduced in this population."

A notable finding, they said, was that the use of statins was associated with a significant reduction of gastrointestinal bleeding (35%) and intracranial bleeding (31%).

The authors said that the incidence of major bleeding events associated with aspirin identified in their study was "much higher" than reported in randomized prospective studies. The 55% increase in the relative risk of major bleeding, over no aspirin, "translates to 2 excess cases for 1,000 patients treated per year," they said. "In other words, the excess number of major bleeding events associated with the use of aspirin is of the same magnitude of the number of major cardiovascular events avoided in the primary prevention setting for individuals with a 10-year risk of between 10% and 20%."

Limitations of their study include the not being able to adjust for all potential factors that can affect bleeding, including over-the-counter aspirin use, although in Italy, low-dose aspirin for CV prevention in high-risk individuals is available by prescription and is fully covered.

Four of the seven authors, including the lead author, reported no disclosures. One author reported receiving a research grant from Bristol-Myers Squibb, another reported receiving a research grant from Bayer, and another reported receiving a research grant and lecture fees, including service on speakers bureaus from Bayer.

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel on May 10 supported the approval of lorcaserin, voting 18-4 with 1 abstention that the potential benefits of the centrally acting drug outweighed its potential risks as a long-term weight loss treatment in obese and overweight people.

At the meeting of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee, panelists voting in favor of approval said that although the weight loss associated with the drug in clinical trials was modest, the results were significant and met one of the FDA criteria for efficacy for a weight loss drug. Although there were some concerns about safety, the panel agreed safety could be followed after approval and recommended that the manufacturer conduct a postmarketing study evaluating cardiovascular outcomes associated with treatment and that patients be monitored for valvular heart disease with echocardiography.

The proposed indication for lorcaserin, at a dosage of 10 mg twice a day, is as an adjunct to diet and exercise for weight management in adults, with a body mass index (BMI) equal to or greater than 30 kg/m² or a BMI equal to or greater than 27 kg/m² if accompanied by weight-related comorbidities.

This is the second time the panel has met to review lorcaserin, a selective serotonin 2C receptor agonist manufactured by Arena Pharmaceuticals Inc., as a treatment for weight loss in obese adults and in overweight adults with comorbidities. At the first meeting in September 2010, the majority of the panel did not support approval, citing an unfavorable risk-benefit ratio, specifically the marginal weight loss with treatment, concerns that the study population was not representative of the real-world population of probable lorcaserin candidates, and unresolved concerns about increases in mammary tumors and astrocytomas in rats exposed to lorcaserin.

Arena resubmitted the application for approval with new data and analyses, including evaluations of rat carcinogenicity data and echocardiographic data evaluating the rate of valvulopathy associated with treatment.

The company provided 1-year data from two phase III studies of 7,190 adults, who did not have diabetes; and a phase III study of 604 patients with type 2 diabetes. Patients were overweight or obese, with BMIs from 27 to 45, and all followed a 600-calorie deficit diet, exercise program, and monthly counseling,

Compared with placebo, those treated with lorcaserin lost significantly more weight, which was associated with significant improvements in glycemic control, lipids, blood pressure, and other metabolic parameters. At 1 year, 47% of those on lorcaserin lost at least 5% of their baseline body weight, compared with 22% of those on placebo. In the study of patients with type 2 diabetes, significantly more of those on lorcaserin also lost at least 5% of their baseline body weight (37.5% vs. 16%); weight loss was associated with significant improvements in glycemic control at 1 year.

The most common side effects associated with treatment included headache, dizziness, nausea, fatigue, and dry mouth. Neuropsychiatric effects, including depression and euphoria, were also more common among those treated with lorcaserin. At 1 year of treatment, the rate of valvulopathy was 2.37% among those on lorcaserin, compared with 2.04% of those on placebo.

Several panelists agreed that the higher rate of valvulopathy associated with treatment was a signal, but they recommended that patients be monitored with echocardiography periodically during treatment to check for valvulopathy. Several panelists said they were reassured that blood pressure and heart rate remained the same or decreased in patients on the drug.

The FDA usually follows the recommendations of its advisory panels. The panelists have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally, a panelist may be given a waiver. At this meeting, one panelist had a potential conflict (he serves on a data safety monitoring board for a competing product with an indication related to the product discussed by the panel), but was granted a waiver because his expertise was considered essential to the meeting and outweighed the potential for a conflict of interest, according to the FDA.

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel on May 10 supported the approval of lorcaserin, voting 18-4 with 1 abstention that the potential benefits of the centrally acting drug outweighed its potential risks as a long-term weight loss treatment in obese and overweight people.

At the meeting of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee, panelists voting in favor of approval said that although the weight loss associated with the drug in clinical trials was modest, the results were significant and met one of the FDA criteria for efficacy for a weight loss drug. Although there were some concerns about safety, the panel agreed safety could be followed after approval and recommended that the manufacturer conduct a postmarketing study evaluating cardiovascular outcomes associated with treatment and that patients be monitored for valvular heart disease with echocardiography.

The proposed indication for lorcaserin, at a dosage of 10 mg twice a day, is as an adjunct to diet and exercise for weight management in adults, with a body mass index (BMI) equal to or greater than 30 kg/m² or a BMI equal to or greater than 27 kg/m² if accompanied by weight-related comorbidities.

This is the second time the panel has met to review lorcaserin, a selective serotonin 2C receptor agonist manufactured by Arena Pharmaceuticals Inc., as a treatment for weight loss in obese adults and in overweight adults with comorbidities. At the first meeting in September 2010, the majority of the panel did not support approval, citing an unfavorable risk-benefit ratio, specifically the marginal weight loss with treatment, concerns that the study population was not representative of the real-world population of probable lorcaserin candidates, and unresolved concerns about increases in mammary tumors and astrocytomas in rats exposed to lorcaserin.

Arena resubmitted the application for approval with new data and analyses, including evaluations of rat carcinogenicity data and echocardiographic data evaluating the rate of valvulopathy associated with treatment.

The company provided 1-year data from two phase III studies of 7,190 adults, who did not have diabetes; and a phase III study of 604 patients with type 2 diabetes. Patients were overweight or obese, with BMIs from 27 to 45, and all followed a 600-calorie deficit diet, exercise program, and monthly counseling,

Compared with placebo, those treated with lorcaserin lost significantly more weight, which was associated with significant improvements in glycemic control, lipids, blood pressure, and other metabolic parameters. At 1 year, 47% of those on lorcaserin lost at least 5% of their baseline body weight, compared with 22% of those on placebo. In the study of patients with type 2 diabetes, significantly more of those on lorcaserin also lost at least 5% of their baseline body weight (37.5% vs. 16%); weight loss was associated with significant improvements in glycemic control at 1 year.

The most common side effects associated with treatment included headache, dizziness, nausea, fatigue, and dry mouth. Neuropsychiatric effects, including depression and euphoria, were also more common among those treated with lorcaserin. At 1 year of treatment, the rate of valvulopathy was 2.37% among those on lorcaserin, compared with 2.04% of those on placebo.

Several panelists agreed that the higher rate of valvulopathy associated with treatment was a signal, but they recommended that patients be monitored with echocardiography periodically during treatment to check for valvulopathy. Several panelists said they were reassured that blood pressure and heart rate remained the same or decreased in patients on the drug.

The FDA usually follows the recommendations of its advisory panels. The panelists have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally, a panelist may be given a waiver. At this meeting, one panelist had a potential conflict (he serves on a data safety monitoring board for a competing product with an indication related to the product discussed by the panel), but was granted a waiver because his expertise was considered essential to the meeting and outweighed the potential for a conflict of interest, according to the FDA.

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel on May 10 supported the approval of lorcaserin, voting 18-4 with 1 abstention that the potential benefits of the centrally acting drug outweighed its potential risks as a long-term weight loss treatment in obese and overweight people.

At the meeting of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee, panelists voting in favor of approval said that although the weight loss associated with the drug in clinical trials was modest, the results were significant and met one of the FDA criteria for efficacy for a weight loss drug. Although there were some concerns about safety, the panel agreed safety could be followed after approval and recommended that the manufacturer conduct a postmarketing study evaluating cardiovascular outcomes associated with treatment and that patients be monitored for valvular heart disease with echocardiography.

The proposed indication for lorcaserin, at a dosage of 10 mg twice a day, is as an adjunct to diet and exercise for weight management in adults, with a body mass index (BMI) equal to or greater than 30 kg/m² or a BMI equal to or greater than 27 kg/m² if accompanied by weight-related comorbidities.

This is the second time the panel has met to review lorcaserin, a selective serotonin 2C receptor agonist manufactured by Arena Pharmaceuticals Inc., as a treatment for weight loss in obese adults and in overweight adults with comorbidities. At the first meeting in September 2010, the majority of the panel did not support approval, citing an unfavorable risk-benefit ratio, specifically the marginal weight loss with treatment, concerns that the study population was not representative of the real-world population of probable lorcaserin candidates, and unresolved concerns about increases in mammary tumors and astrocytomas in rats exposed to lorcaserin.

Arena resubmitted the application for approval with new data and analyses, including evaluations of rat carcinogenicity data and echocardiographic data evaluating the rate of valvulopathy associated with treatment.

The company provided 1-year data from two phase III studies of 7,190 adults, who did not have diabetes; and a phase III study of 604 patients with type 2 diabetes. Patients were overweight or obese, with BMIs from 27 to 45, and all followed a 600-calorie deficit diet, exercise program, and monthly counseling,

Compared with placebo, those treated with lorcaserin lost significantly more weight, which was associated with significant improvements in glycemic control, lipids, blood pressure, and other metabolic parameters. At 1 year, 47% of those on lorcaserin lost at least 5% of their baseline body weight, compared with 22% of those on placebo. In the study of patients with type 2 diabetes, significantly more of those on lorcaserin also lost at least 5% of their baseline body weight (37.5% vs. 16%); weight loss was associated with significant improvements in glycemic control at 1 year.

The most common side effects associated with treatment included headache, dizziness, nausea, fatigue, and dry mouth. Neuropsychiatric effects, including depression and euphoria, were also more common among those treated with lorcaserin. At 1 year of treatment, the rate of valvulopathy was 2.37% among those on lorcaserin, compared with 2.04% of those on placebo.

Several panelists agreed that the higher rate of valvulopathy associated with treatment was a signal, but they recommended that patients be monitored with echocardiography periodically during treatment to check for valvulopathy. Several panelists said they were reassured that blood pressure and heart rate remained the same or decreased in patients on the drug.

The FDA usually follows the recommendations of its advisory panels. The panelists have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally, a panelist may be given a waiver. At this meeting, one panelist had a potential conflict (he serves on a data safety monitoring board for a competing product with an indication related to the product discussed by the panel), but was granted a waiver because his expertise was considered essential to the meeting and outweighed the potential for a conflict of interest, according to the FDA.

ORLANDO – Gastroesophageal reflux disease was associated with prior wheezing and greater severity of infant acute respiratory illness in a study involving 430 term, healthy infants presenting with acute respiratory illness due to bronchiolitis or upper respiratory infection.

New-onset gastroesophageal reflux disease (GERD) during bronchiolitis in previously health infants has been shown to increase the risk for respiratory failure (Acta Paediatr. 2007;96:1025-9). Bronchiolitis is a prominent risk factor for childhood asthma, and GERD is associated with worsened asthma severity (J. Asthma 2011;48:366-73). As yet unknown is whether preexisting GERD (clinically significant reflux) in infants modulates the severity of infant bronchiolitis or the diagnosis of childhood asthma, Dr. Robert S. Valet of Vanderbilt University, Nashville, Tenn., and his associates said in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The 430 infants, aged 0-12 months, were enrolled in the Tennessee Children\'s Respiratory Initiative. The presence of infant GERD was defined by parental report with an answer of "yes" to the question, "Does your child have a history of gastroesophageal reflux disease?"

In all, 45 infants (10%) were reported to have GERD. They were more likely than those without GERD to be white and to have a family history of allergic rhinitis, but did not differ by age at illness, secondhand smoke (SHS) exposure, or family history of asthma. The group with GERD was significantly more likely to have previous treatment for wheeze (42% vs. 25%), and to have bronchiolitis (84% vs. 71%).

The median bronchiolitis severity score (range, 0-12; higher score indicates more severe disease, with a difference of 0.5 being clinically meaningful) in univariate analysis was 5.5 in the GERD group vs. 4.0 in infants without GERD. Adjusting for age, race, sex, and SHS, the increased bronchiolitis severity score in the GERD group persisted (odds ratio, 1.90). Although not significant, 11% of infants with GERD vs. 5% of non-GERD infants needed ICU care, Dr. Valet and his associates reported.

Preexisting GERD was associated with increased bronchiolitis severity and increased recurrent wheezing illness at 2 years, at which time 69% of infants with GERD and 46% of those without GERD had experienced wheeze since initial study enrollment (OR, 2.35; P = .006). And although not statistically significant, 52% with GERD vs. 40% without had used albuterol in this time period (P = .13). However, there was no difference in asthma diagnosis at age 2 years; 24% of infants with GERD were diagnosed with asthma by age 2, compared with 22% of those without GERD (P = .76).

This is the first time that preexisting infant GERD has been associated with increased bronchiolitis severity, Dr. Valet noted. Future study could investigate whether treating infant GERD decreases both bronchiolitis and asthma severity. "These findings should be replicated using a more rigorous assessment of GERD," he concluded.

The study was funded by the Thrasher Research Fund. Dr. Valet said he had no relevant financial disclosures.

ORLANDO – Gastroesophageal reflux disease was associated with prior wheezing and greater severity of infant acute respiratory illness in a study involving 430 term, healthy infants presenting with acute respiratory illness due to bronchiolitis or upper respiratory infection.

New-onset gastroesophageal reflux disease (GERD) during bronchiolitis in previously health infants has been shown to increase the risk for respiratory failure (Acta Paediatr. 2007;96:1025-9). Bronchiolitis is a prominent risk factor for childhood asthma, and GERD is associated with worsened asthma severity (J. Asthma 2011;48:366-73). As yet unknown is whether preexisting GERD (clinically significant reflux) in infants modulates the severity of infant bronchiolitis or the diagnosis of childhood asthma, Dr. Robert S. Valet of Vanderbilt University, Nashville, Tenn., and his associates said in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The 430 infants, aged 0-12 months, were enrolled in the Tennessee Children\'s Respiratory Initiative. The presence of infant GERD was defined by parental report with an answer of "yes" to the question, "Does your child have a history of gastroesophageal reflux disease?"

In all, 45 infants (10%) were reported to have GERD. They were more likely than those without GERD to be white and to have a family history of allergic rhinitis, but did not differ by age at illness, secondhand smoke (SHS) exposure, or family history of asthma. The group with GERD was significantly more likely to have previous treatment for wheeze (42% vs. 25%), and to have bronchiolitis (84% vs. 71%).

The median bronchiolitis severity score (range, 0-12; higher score indicates more severe disease, with a difference of 0.5 being clinically meaningful) in univariate analysis was 5.5 in the GERD group vs. 4.0 in infants without GERD. Adjusting for age, race, sex, and SHS, the increased bronchiolitis severity score in the GERD group persisted (odds ratio, 1.90). Although not significant, 11% of infants with GERD vs. 5% of non-GERD infants needed ICU care, Dr. Valet and his associates reported.

Preexisting GERD was associated with increased bronchiolitis severity and increased recurrent wheezing illness at 2 years, at which time 69% of infants with GERD and 46% of those without GERD had experienced wheeze since initial study enrollment (OR, 2.35; P = .006). And although not statistically significant, 52% with GERD vs. 40% without had used albuterol in this time period (P = .13). However, there was no difference in asthma diagnosis at age 2 years; 24% of infants with GERD were diagnosed with asthma by age 2, compared with 22% of those without GERD (P = .76).

This is the first time that preexisting infant GERD has been associated with increased bronchiolitis severity, Dr. Valet noted. Future study could investigate whether treating infant GERD decreases both bronchiolitis and asthma severity. "These findings should be replicated using a more rigorous assessment of GERD," he concluded.

The study was funded by the Thrasher Research Fund. Dr. Valet said he had no relevant financial disclosures.

ORLANDO – Gastroesophageal reflux disease was associated with prior wheezing and greater severity of infant acute respiratory illness in a study involving 430 term, healthy infants presenting with acute respiratory illness due to bronchiolitis or upper respiratory infection.

New-onset gastroesophageal reflux disease (GERD) during bronchiolitis in previously health infants has been shown to increase the risk for respiratory failure (Acta Paediatr. 2007;96:1025-9). Bronchiolitis is a prominent risk factor for childhood asthma, and GERD is associated with worsened asthma severity (J. Asthma 2011;48:366-73). As yet unknown is whether preexisting GERD (clinically significant reflux) in infants modulates the severity of infant bronchiolitis or the diagnosis of childhood asthma, Dr. Robert S. Valet of Vanderbilt University, Nashville, Tenn., and his associates said in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The 430 infants, aged 0-12 months, were enrolled in the Tennessee Children\'s Respiratory Initiative. The presence of infant GERD was defined by parental report with an answer of "yes" to the question, "Does your child have a history of gastroesophageal reflux disease?"

In all, 45 infants (10%) were reported to have GERD. They were more likely than those without GERD to be white and to have a family history of allergic rhinitis, but did not differ by age at illness, secondhand smoke (SHS) exposure, or family history of asthma. The group with GERD was significantly more likely to have previous treatment for wheeze (42% vs. 25%), and to have bronchiolitis (84% vs. 71%).

The median bronchiolitis severity score (range, 0-12; higher score indicates more severe disease, with a difference of 0.5 being clinically meaningful) in univariate analysis was 5.5 in the GERD group vs. 4.0 in infants without GERD. Adjusting for age, race, sex, and SHS, the increased bronchiolitis severity score in the GERD group persisted (odds ratio, 1.90). Although not significant, 11% of infants with GERD vs. 5% of non-GERD infants needed ICU care, Dr. Valet and his associates reported.

Preexisting GERD was associated with increased bronchiolitis severity and increased recurrent wheezing illness at 2 years, at which time 69% of infants with GERD and 46% of those without GERD had experienced wheeze since initial study enrollment (OR, 2.35; P = .006). And although not statistically significant, 52% with GERD vs. 40% without had used albuterol in this time period (P = .13). However, there was no difference in asthma diagnosis at age 2 years; 24% of infants with GERD were diagnosed with asthma by age 2, compared with 22% of those without GERD (P = .76).

This is the first time that preexisting infant GERD has been associated with increased bronchiolitis severity, Dr. Valet noted. Future study could investigate whether treating infant GERD decreases both bronchiolitis and asthma severity. "These findings should be replicated using a more rigorous assessment of GERD," he concluded.

The study was funded by the Thrasher Research Fund. Dr. Valet said he had no relevant financial disclosures.