American Thoracic Society (ATS): International Conference 2014

SAN DIEGO – Twelve weeks of rosuvastatin therapy was associated with reduced systemic inflammation, but no improvement in pulmonary function in a randomized, placebo-controlled trial in 99 patients with stable chronic obstructive pulmonary disease.

However, a prespecified analysis of patients with elevated results on high-sensitivity C-reactive protein tests (hsCRP) found that those with levels higher than the median of 1.7 mg/dL at baseline showed improved endothelial function with the statin, compared with placebo, Dr. Anke Neukamm reported at an international conference of the American Thoracic Society.

The findings provided a small ray of positivity for the anti-inflammatory effects of statins in chronic obstructive pulmonary disease (COPD) on a day when two larger randomized, controlled studies reported that rosuvastatin did not reduce mortality in patients with sepsis-associated acute respiratory distress syndrome and simvastatin did not reduce exacerbations in patients with moderate to severe COPD.

Dr. Neukamm’s RODEO study (Effect of Rosuvastatin Treatment in Patients With Stable Chronic Obstructive Pulmonary Disease) randomized patients with stable chronic COPD to once-daily rosuvastatin 10 mg or placebo for 12 weeks. The groups did not differ significantly in the primary endpoint peripheral vasodilator function expressed as a reactive hyperemia ratio. In the subgroup analysis of patients with elevated hsCRP levels, however, the reactive hyperemia index improved from approximately 2.5 at baseline to 2.8 after 12 weeks of rosuvastatin and worsened from 2.6 to 2.5 in the placebo group, leaving a statistically significant difference between groups at the end of treatment, said Dr. Neukamm of Akershus University Hospital, Lørenskog, Norway.

This suggested "a clear improvement of endothelial function in the statin group," she said.

Some physicians in the audience disputed the results, noting that rosuvastatin’s effects would not have reached statistical significance if endothelial function had not worsened in the placebo group.

Dr. Neukamm remained cautiously optimistic. Targeting statin therapy for patients with COPD to those with increased systemic inflammation as indicated by elevated hsCRP levels might improve vascular function, she said in an interview. Patients in the study were "a very select group with a lower cardiovascular risk" than patients in other COPD studies. Without larger prospective trials, "we don’t know if this small improvement in endothelial function would translate" into better clinical outcomes, she said.

Among secondary endpoints, circulating hsCRP levels decreased from 1.4 mg/L at baseline to 1.2 mg/L in the rosuvastatin group, compared with a change from 1.8 mg/L to 2.2 mg/L in the placebo group. The difference between groups was significant. Levels of the inflammatory marker interleukin-6 remained stable at 4.1 pg/mL in the statin group and increased from 3.4 pg/mL to 4.4 pg/mL in the placebo group, also a significant difference between groups.

The trial excluded patients with a history of coronary artery disease, other diagnosed lung disease (except asthma), uncontrolled arterial hypertension, or diabetes, or patients who had used statins in the prior 4 weeks or who had a clear indication for statin use.

Thirty-three adverse events included COPD acute exacerbations, constipation, diarrhea, nausea, myalgia, and vertigo. Seven serious adverse events included hospitalizations for COPD exacerbations, atrial flutter in one patient, and pituitary apoplexy in one patient.

Patients had a mean age of 65 years, 48% were female, and 25% had a history of hypertension. They had a smoking history of a mean 37 pack-years. Baseline patient characteristics were similar between groups except for a higher percentage of current smokers in the placebo group (49%), compared with the rosuvastatin group (26%).

Stable COPD and acute exacerbations have been associated with systemic inflammation as reflected in increased levels of CRP and other inflammatory markers. Cardiovascular disease is a major comorbidity in patients with COPD, and inflammation is a hallmark of the atherosclerotic process, Dr. Neukamm said. Endothelial dysfunction, which is an early predictor of atherosclerosis, has been shown to be increased in patients with COPD.

A previous observational study of 2,708 patients with COPD suggested that long-term statin therapy was associated with a significant 78% decrease in mortality in those with hsCRP levels greater than 3 mg/L and a nonsignificant 21% decreased mortality in those with lower hsCRP levels (Pulm. Pharmacol. Ther. 2013;26:212-7).

The study was funded by the Norwegian Extra Foundation for Health and Rehabilitation and by AstraZeneca, which makes a brand name formulation of rosuvastatin. Dr. Neukamm has been a speaker for AstraZeneca.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

SAN DIEGO – Twelve weeks of rosuvastatin therapy was associated with reduced systemic inflammation, but no improvement in pulmonary function in a randomized, placebo-controlled trial in 99 patients with stable chronic obstructive pulmonary disease.

However, a prespecified analysis of patients with elevated results on high-sensitivity C-reactive protein tests (hsCRP) found that those with levels higher than the median of 1.7 mg/dL at baseline showed improved endothelial function with the statin, compared with placebo, Dr. Anke Neukamm reported at an international conference of the American Thoracic Society.

The findings provided a small ray of positivity for the anti-inflammatory effects of statins in chronic obstructive pulmonary disease (COPD) on a day when two larger randomized, controlled studies reported that rosuvastatin did not reduce mortality in patients with sepsis-associated acute respiratory distress syndrome and simvastatin did not reduce exacerbations in patients with moderate to severe COPD.

Dr. Neukamm’s RODEO study (Effect of Rosuvastatin Treatment in Patients With Stable Chronic Obstructive Pulmonary Disease) randomized patients with stable chronic COPD to once-daily rosuvastatin 10 mg or placebo for 12 weeks. The groups did not differ significantly in the primary endpoint peripheral vasodilator function expressed as a reactive hyperemia ratio. In the subgroup analysis of patients with elevated hsCRP levels, however, the reactive hyperemia index improved from approximately 2.5 at baseline to 2.8 after 12 weeks of rosuvastatin and worsened from 2.6 to 2.5 in the placebo group, leaving a statistically significant difference between groups at the end of treatment, said Dr. Neukamm of Akershus University Hospital, Lørenskog, Norway.

This suggested "a clear improvement of endothelial function in the statin group," she said.

Some physicians in the audience disputed the results, noting that rosuvastatin’s effects would not have reached statistical significance if endothelial function had not worsened in the placebo group.

Dr. Neukamm remained cautiously optimistic. Targeting statin therapy for patients with COPD to those with increased systemic inflammation as indicated by elevated hsCRP levels might improve vascular function, she said in an interview. Patients in the study were "a very select group with a lower cardiovascular risk" than patients in other COPD studies. Without larger prospective trials, "we don’t know if this small improvement in endothelial function would translate" into better clinical outcomes, she said.

Among secondary endpoints, circulating hsCRP levels decreased from 1.4 mg/L at baseline to 1.2 mg/L in the rosuvastatin group, compared with a change from 1.8 mg/L to 2.2 mg/L in the placebo group. The difference between groups was significant. Levels of the inflammatory marker interleukin-6 remained stable at 4.1 pg/mL in the statin group and increased from 3.4 pg/mL to 4.4 pg/mL in the placebo group, also a significant difference between groups.

The trial excluded patients with a history of coronary artery disease, other diagnosed lung disease (except asthma), uncontrolled arterial hypertension, or diabetes, or patients who had used statins in the prior 4 weeks or who had a clear indication for statin use.

Thirty-three adverse events included COPD acute exacerbations, constipation, diarrhea, nausea, myalgia, and vertigo. Seven serious adverse events included hospitalizations for COPD exacerbations, atrial flutter in one patient, and pituitary apoplexy in one patient.

Patients had a mean age of 65 years, 48% were female, and 25% had a history of hypertension. They had a smoking history of a mean 37 pack-years. Baseline patient characteristics were similar between groups except for a higher percentage of current smokers in the placebo group (49%), compared with the rosuvastatin group (26%).

Stable COPD and acute exacerbations have been associated with systemic inflammation as reflected in increased levels of CRP and other inflammatory markers. Cardiovascular disease is a major comorbidity in patients with COPD, and inflammation is a hallmark of the atherosclerotic process, Dr. Neukamm said. Endothelial dysfunction, which is an early predictor of atherosclerosis, has been shown to be increased in patients with COPD.

A previous observational study of 2,708 patients with COPD suggested that long-term statin therapy was associated with a significant 78% decrease in mortality in those with hsCRP levels greater than 3 mg/L and a nonsignificant 21% decreased mortality in those with lower hsCRP levels (Pulm. Pharmacol. Ther. 2013;26:212-7).

The study was funded by the Norwegian Extra Foundation for Health and Rehabilitation and by AstraZeneca, which makes a brand name formulation of rosuvastatin. Dr. Neukamm has been a speaker for AstraZeneca.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

SAN DIEGO – Twelve weeks of rosuvastatin therapy was associated with reduced systemic inflammation, but no improvement in pulmonary function in a randomized, placebo-controlled trial in 99 patients with stable chronic obstructive pulmonary disease.

However, a prespecified analysis of patients with elevated results on high-sensitivity C-reactive protein tests (hsCRP) found that those with levels higher than the median of 1.7 mg/dL at baseline showed improved endothelial function with the statin, compared with placebo, Dr. Anke Neukamm reported at an international conference of the American Thoracic Society.

The findings provided a small ray of positivity for the anti-inflammatory effects of statins in chronic obstructive pulmonary disease (COPD) on a day when two larger randomized, controlled studies reported that rosuvastatin did not reduce mortality in patients with sepsis-associated acute respiratory distress syndrome and simvastatin did not reduce exacerbations in patients with moderate to severe COPD.

Dr. Neukamm’s RODEO study (Effect of Rosuvastatin Treatment in Patients With Stable Chronic Obstructive Pulmonary Disease) randomized patients with stable chronic COPD to once-daily rosuvastatin 10 mg or placebo for 12 weeks. The groups did not differ significantly in the primary endpoint peripheral vasodilator function expressed as a reactive hyperemia ratio. In the subgroup analysis of patients with elevated hsCRP levels, however, the reactive hyperemia index improved from approximately 2.5 at baseline to 2.8 after 12 weeks of rosuvastatin and worsened from 2.6 to 2.5 in the placebo group, leaving a statistically significant difference between groups at the end of treatment, said Dr. Neukamm of Akershus University Hospital, Lørenskog, Norway.

This suggested "a clear improvement of endothelial function in the statin group," she said.

Some physicians in the audience disputed the results, noting that rosuvastatin’s effects would not have reached statistical significance if endothelial function had not worsened in the placebo group.

Dr. Neukamm remained cautiously optimistic. Targeting statin therapy for patients with COPD to those with increased systemic inflammation as indicated by elevated hsCRP levels might improve vascular function, she said in an interview. Patients in the study were "a very select group with a lower cardiovascular risk" than patients in other COPD studies. Without larger prospective trials, "we don’t know if this small improvement in endothelial function would translate" into better clinical outcomes, she said.

Among secondary endpoints, circulating hsCRP levels decreased from 1.4 mg/L at baseline to 1.2 mg/L in the rosuvastatin group, compared with a change from 1.8 mg/L to 2.2 mg/L in the placebo group. The difference between groups was significant. Levels of the inflammatory marker interleukin-6 remained stable at 4.1 pg/mL in the statin group and increased from 3.4 pg/mL to 4.4 pg/mL in the placebo group, also a significant difference between groups.

The trial excluded patients with a history of coronary artery disease, other diagnosed lung disease (except asthma), uncontrolled arterial hypertension, or diabetes, or patients who had used statins in the prior 4 weeks or who had a clear indication for statin use.

Thirty-three adverse events included COPD acute exacerbations, constipation, diarrhea, nausea, myalgia, and vertigo. Seven serious adverse events included hospitalizations for COPD exacerbations, atrial flutter in one patient, and pituitary apoplexy in one patient.

Patients had a mean age of 65 years, 48% were female, and 25% had a history of hypertension. They had a smoking history of a mean 37 pack-years. Baseline patient characteristics were similar between groups except for a higher percentage of current smokers in the placebo group (49%), compared with the rosuvastatin group (26%).

Stable COPD and acute exacerbations have been associated with systemic inflammation as reflected in increased levels of CRP and other inflammatory markers. Cardiovascular disease is a major comorbidity in patients with COPD, and inflammation is a hallmark of the atherosclerotic process, Dr. Neukamm said. Endothelial dysfunction, which is an early predictor of atherosclerosis, has been shown to be increased in patients with COPD.

A previous observational study of 2,708 patients with COPD suggested that long-term statin therapy was associated with a significant 78% decrease in mortality in those with hsCRP levels greater than 3 mg/L and a nonsignificant 21% decreased mortality in those with lower hsCRP levels (Pulm. Pharmacol. Ther. 2013;26:212-7).

The study was funded by the Norwegian Extra Foundation for Health and Rehabilitation and by AstraZeneca, which makes a brand name formulation of rosuvastatin. Dr. Neukamm has been a speaker for AstraZeneca.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

SAN DIEGO – Two separate prospective, multicenter trials of statins stopped early when interim results showed they did not help – and potentially harmed – patients with moderate to severe chronic obstructive pulmonary disease or sepsis-associated acute respiratory distress syndrome.

The findings contradict previous observational data suggesting that the potential anti-inflammatory effects of statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (HMG-CoA) might benefit patients with these two diseases.

Statins did not significantly reduce rates of exacerbation of chronic obstructive pulmonary disease (COPD) or the time to first exacerbation in a study of 885 patients with moderate-to-severe COPD who were at high risk for exacerbations and who did not require statins for other indications. Patients in the STATCOPE trial (Prospective Randomized Placebo-Controlled Trial of Simvastatin in the Prevention of COPD) received a daily oral dose of either 40 mg simvastatin or placebo for 12-36 months.

The simvastatin group had a mean of 1.36 exacerbations/person-year, compared with 1.39/person-year in the placebo group. The median number of days to the first exacerbation was 223 on simvastatin and 231 on placebo, differences that were not significant, Dr. Gerard J. Criner and his associates reported at an international conference of the American Thoracic Society.

The results were published online by the New England Journal of Medicine (2014 May 18 [doi:10.1056/NEJMoa1403086]).

Among the 885 patients for whom follow-up information was available, 1,982 acute COPD exacerbations occurred, 965 in 430 patients on simvastatin and 1,017 exacerbations in 447 patients on placebo, said Dr. Criner, professor of medicine and director of the medical intensive care unit and the ventilator rehabilitation unit at Temple University, Philadelphia.

Overall, 34% of patients had three or more exacerbations of COPD, with similar numbers in each group – 141 in the simvastatin group and 155 in the placebo groups. The proportions of patients who received glucocorticoid therapy or antibiotics for exacerbations did not differ significantly between groups.

The simvastatin group had a significantly higher rate of nonfatal serious adverse events involving the GI tract (mainly nausea and bloating from simvastatin) in 30 patients (0.05 events/person-year), compared with events in 17 patients on placebo (0.02 events/person-year). Rates of other nonfatal adverse events were similar between groups, with pneumonia and other respiratory and cardiovascular events most common. Twenty-eight patients on simvastatin and 30 on placebo died.

Asked why he thinks the STATCOPE trial’s negative results didn’t confirm previous positive findings from observational studies including thousands of patients, Dr. Criner speculated that excluding patients with indications for statins may have removed patients with cardiovascular risks who were included in other studies. "I think a lot of the problems we’re seeing for exacerbations in COPD might be related to cardiovascular events in patients who aren’t appropriately treated with statins, who should be," he said.

Rosuvastatin sags in SAILS trial

In the separate double-blind SAILS trial (Statins for Acutely Injured Lungs [ARDS] From Sepsis), enteral rosuvastatin did not decrease mortality, compared with placebo, in 745 patients with sepsis-associated acute respiratory distress syndrome (ARDS). Dr. Jonathon D. Truwit and his associates are scheduled to report the results at the meeting on Tuesday. The findings also appeared online in the New England Journal of Medicine (2014 May 18 [doi:10.1056/NEJMoa1401520]).

Researchers found that 28.5% of patients on rosuvastatin and 25% on placebo died before hospital discharge or within 60 days if the patient was still in a health care facility, reported Dr. Truwit, professor of medicine at the Medical College of Wisconsin, Madison.

Patients in the rosuvastatin group received a loading dose of 40 mg followed by daily maintenance doses of 20 mg (or 10 mg for patients with a morning serum creatinine level of 2.8 mg/dL or more who were not receiving renal replacement therapy. Treatment continued until the third day of discharge from the ICU, hospital discharge, or death, whichever came first.

Both the rosuvastatin and placebo groups had a mean of 15 ventilator-free days.

Results also did not differ significantly between groups for the 339 patients who were in shock at the start of the study or for 109 patients who had used statins before the study and who underwent a 48-hour washout period before randomization.

Patients on rosuvastatin had a mean of 10.1 days free of renal failure and 10.8 days free of hepatic failure within the first 14 days, both significantly fewer compared with patients on placebo (11 and 11.8 days, respectively). "These differences in organ-failure-free days were small, and their significance may be spurious owing to the number of secondary endpoints analyzed. However, we cannot rule out a detrimental effect of rosuvastatin," the investigators wrote.

The results, combined with previous smaller randomized trials of other statins, suggest no benefits from starting or continuing statin therapy for sepsis-associated ARDS, Dr. Truwit said.

"The finding in observational studies that previous statin use provides a benefit may reflect better access to health care among patients who use statins than among those who do not, with a shorter time to the initiation of antibiotic therapy at the onset of symptoms of infection in statin users," according to the journal article.

The National Heart, Lung, and Blood Institute and the Canadian Institutes of Health Research funded the STATCOPE trial. The investigators reported financial associations with dozens of companies, including five of Dr. Criner’s coinvestigators who had financial associations with Merck, which makes simvastatin. The SAILS trial was sponsored by the NHLBI and by AstraZeneca, which makes rosuvastatin. Dr. Truwit reported having no financial disclosures. Three of his coinvestigators reported financial ties to AstraZeneca, and four reported associations with a total of 14 other companies.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

SAN DIEGO – Two separate prospective, multicenter trials of statins stopped early when interim results showed they did not help – and potentially harmed – patients with moderate to severe chronic obstructive pulmonary disease or sepsis-associated acute respiratory distress syndrome.

The findings contradict previous observational data suggesting that the potential anti-inflammatory effects of statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (HMG-CoA) might benefit patients with these two diseases.

Statins did not significantly reduce rates of exacerbation of chronic obstructive pulmonary disease (COPD) or the time to first exacerbation in a study of 885 patients with moderate-to-severe COPD who were at high risk for exacerbations and who did not require statins for other indications. Patients in the STATCOPE trial (Prospective Randomized Placebo-Controlled Trial of Simvastatin in the Prevention of COPD) received a daily oral dose of either 40 mg simvastatin or placebo for 12-36 months.

The simvastatin group had a mean of 1.36 exacerbations/person-year, compared with 1.39/person-year in the placebo group. The median number of days to the first exacerbation was 223 on simvastatin and 231 on placebo, differences that were not significant, Dr. Gerard J. Criner and his associates reported at an international conference of the American Thoracic Society.

The results were published online by the New England Journal of Medicine (2014 May 18 [doi:10.1056/NEJMoa1403086]).

Among the 885 patients for whom follow-up information was available, 1,982 acute COPD exacerbations occurred, 965 in 430 patients on simvastatin and 1,017 exacerbations in 447 patients on placebo, said Dr. Criner, professor of medicine and director of the medical intensive care unit and the ventilator rehabilitation unit at Temple University, Philadelphia.

Overall, 34% of patients had three or more exacerbations of COPD, with similar numbers in each group – 141 in the simvastatin group and 155 in the placebo groups. The proportions of patients who received glucocorticoid therapy or antibiotics for exacerbations did not differ significantly between groups.

The simvastatin group had a significantly higher rate of nonfatal serious adverse events involving the GI tract (mainly nausea and bloating from simvastatin) in 30 patients (0.05 events/person-year), compared with events in 17 patients on placebo (0.02 events/person-year). Rates of other nonfatal adverse events were similar between groups, with pneumonia and other respiratory and cardiovascular events most common. Twenty-eight patients on simvastatin and 30 on placebo died.

Asked why he thinks the STATCOPE trial’s negative results didn’t confirm previous positive findings from observational studies including thousands of patients, Dr. Criner speculated that excluding patients with indications for statins may have removed patients with cardiovascular risks who were included in other studies. "I think a lot of the problems we’re seeing for exacerbations in COPD might be related to cardiovascular events in patients who aren’t appropriately treated with statins, who should be," he said.

Rosuvastatin sags in SAILS trial

In the separate double-blind SAILS trial (Statins for Acutely Injured Lungs [ARDS] From Sepsis), enteral rosuvastatin did not decrease mortality, compared with placebo, in 745 patients with sepsis-associated acute respiratory distress syndrome (ARDS). Dr. Jonathon D. Truwit and his associates are scheduled to report the results at the meeting on Tuesday. The findings also appeared online in the New England Journal of Medicine (2014 May 18 [doi:10.1056/NEJMoa1401520]).

Researchers found that 28.5% of patients on rosuvastatin and 25% on placebo died before hospital discharge or within 60 days if the patient was still in a health care facility, reported Dr. Truwit, professor of medicine at the Medical College of Wisconsin, Madison.

Patients in the rosuvastatin group received a loading dose of 40 mg followed by daily maintenance doses of 20 mg (or 10 mg for patients with a morning serum creatinine level of 2.8 mg/dL or more who were not receiving renal replacement therapy. Treatment continued until the third day of discharge from the ICU, hospital discharge, or death, whichever came first.

Both the rosuvastatin and placebo groups had a mean of 15 ventilator-free days.

Results also did not differ significantly between groups for the 339 patients who were in shock at the start of the study or for 109 patients who had used statins before the study and who underwent a 48-hour washout period before randomization.

Patients on rosuvastatin had a mean of 10.1 days free of renal failure and 10.8 days free of hepatic failure within the first 14 days, both significantly fewer compared with patients on placebo (11 and 11.8 days, respectively). "These differences in organ-failure-free days were small, and their significance may be spurious owing to the number of secondary endpoints analyzed. However, we cannot rule out a detrimental effect of rosuvastatin," the investigators wrote.

The results, combined with previous smaller randomized trials of other statins, suggest no benefits from starting or continuing statin therapy for sepsis-associated ARDS, Dr. Truwit said.

"The finding in observational studies that previous statin use provides a benefit may reflect better access to health care among patients who use statins than among those who do not, with a shorter time to the initiation of antibiotic therapy at the onset of symptoms of infection in statin users," according to the journal article.

The National Heart, Lung, and Blood Institute and the Canadian Institutes of Health Research funded the STATCOPE trial. The investigators reported financial associations with dozens of companies, including five of Dr. Criner’s coinvestigators who had financial associations with Merck, which makes simvastatin. The SAILS trial was sponsored by the NHLBI and by AstraZeneca, which makes rosuvastatin. Dr. Truwit reported having no financial disclosures. Three of his coinvestigators reported financial ties to AstraZeneca, and four reported associations with a total of 14 other companies.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

SAN DIEGO – Two separate prospective, multicenter trials of statins stopped early when interim results showed they did not help – and potentially harmed – patients with moderate to severe chronic obstructive pulmonary disease or sepsis-associated acute respiratory distress syndrome.

The findings contradict previous observational data suggesting that the potential anti-inflammatory effects of statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (HMG-CoA) might benefit patients with these two diseases.

Statins did not significantly reduce rates of exacerbation of chronic obstructive pulmonary disease (COPD) or the time to first exacerbation in a study of 885 patients with moderate-to-severe COPD who were at high risk for exacerbations and who did not require statins for other indications. Patients in the STATCOPE trial (Prospective Randomized Placebo-Controlled Trial of Simvastatin in the Prevention of COPD) received a daily oral dose of either 40 mg simvastatin or placebo for 12-36 months.

The simvastatin group had a mean of 1.36 exacerbations/person-year, compared with 1.39/person-year in the placebo group. The median number of days to the first exacerbation was 223 on simvastatin and 231 on placebo, differences that were not significant, Dr. Gerard J. Criner and his associates reported at an international conference of the American Thoracic Society.

The results were published online by the New England Journal of Medicine (2014 May 18 [doi:10.1056/NEJMoa1403086]).

Among the 885 patients for whom follow-up information was available, 1,982 acute COPD exacerbations occurred, 965 in 430 patients on simvastatin and 1,017 exacerbations in 447 patients on placebo, said Dr. Criner, professor of medicine and director of the medical intensive care unit and the ventilator rehabilitation unit at Temple University, Philadelphia.

Overall, 34% of patients had three or more exacerbations of COPD, with similar numbers in each group – 141 in the simvastatin group and 155 in the placebo groups. The proportions of patients who received glucocorticoid therapy or antibiotics for exacerbations did not differ significantly between groups.

The simvastatin group had a significantly higher rate of nonfatal serious adverse events involving the GI tract (mainly nausea and bloating from simvastatin) in 30 patients (0.05 events/person-year), compared with events in 17 patients on placebo (0.02 events/person-year). Rates of other nonfatal adverse events were similar between groups, with pneumonia and other respiratory and cardiovascular events most common. Twenty-eight patients on simvastatin and 30 on placebo died.

Asked why he thinks the STATCOPE trial’s negative results didn’t confirm previous positive findings from observational studies including thousands of patients, Dr. Criner speculated that excluding patients with indications for statins may have removed patients with cardiovascular risks who were included in other studies. "I think a lot of the problems we’re seeing for exacerbations in COPD might be related to cardiovascular events in patients who aren’t appropriately treated with statins, who should be," he said.

Rosuvastatin sags in SAILS trial

In the separate double-blind SAILS trial (Statins for Acutely Injured Lungs [ARDS] From Sepsis), enteral rosuvastatin did not decrease mortality, compared with placebo, in 745 patients with sepsis-associated acute respiratory distress syndrome (ARDS). Dr. Jonathon D. Truwit and his associates are scheduled to report the results at the meeting on Tuesday. The findings also appeared online in the New England Journal of Medicine (2014 May 18 [doi:10.1056/NEJMoa1401520]).

Researchers found that 28.5% of patients on rosuvastatin and 25% on placebo died before hospital discharge or within 60 days if the patient was still in a health care facility, reported Dr. Truwit, professor of medicine at the Medical College of Wisconsin, Madison.

Patients in the rosuvastatin group received a loading dose of 40 mg followed by daily maintenance doses of 20 mg (or 10 mg for patients with a morning serum creatinine level of 2.8 mg/dL or more who were not receiving renal replacement therapy. Treatment continued until the third day of discharge from the ICU, hospital discharge, or death, whichever came first.

Both the rosuvastatin and placebo groups had a mean of 15 ventilator-free days.

Results also did not differ significantly between groups for the 339 patients who were in shock at the start of the study or for 109 patients who had used statins before the study and who underwent a 48-hour washout period before randomization.

Patients on rosuvastatin had a mean of 10.1 days free of renal failure and 10.8 days free of hepatic failure within the first 14 days, both significantly fewer compared with patients on placebo (11 and 11.8 days, respectively). "These differences in organ-failure-free days were small, and their significance may be spurious owing to the number of secondary endpoints analyzed. However, we cannot rule out a detrimental effect of rosuvastatin," the investigators wrote.

The results, combined with previous smaller randomized trials of other statins, suggest no benefits from starting or continuing statin therapy for sepsis-associated ARDS, Dr. Truwit said.

"The finding in observational studies that previous statin use provides a benefit may reflect better access to health care among patients who use statins than among those who do not, with a shorter time to the initiation of antibiotic therapy at the onset of symptoms of infection in statin users," according to the journal article.

The National Heart, Lung, and Blood Institute and the Canadian Institutes of Health Research funded the STATCOPE trial. The investigators reported financial associations with dozens of companies, including five of Dr. Criner’s coinvestigators who had financial associations with Merck, which makes simvastatin. The SAILS trial was sponsored by the NHLBI and by AstraZeneca, which makes rosuvastatin. Dr. Truwit reported having no financial disclosures. Three of his coinvestigators reported financial ties to AstraZeneca, and four reported associations with a total of 14 other companies.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert