Statin reduces MI risk in ischemic heart failure

DALLAS – Rosuvastatin appears to reduce the risk of acute myocardial infarction in patients with ischemic heart failure, according to a meta-analysis of two landmark statin trials.

This finding is at odds with current thinking as expressed in the new American Heart Association/American College of Cardiology (AHA/ACC) guidelines, which don’t specifically recommend statin therapy for heart failure patients because no large randomized trials have shown a significant reduction in cardiovascular events.

That’s probably because those studies relied on traditional statistical techniques of survival analysis rather than the less familiar method of competing risk analysis, which is better suited to detecting a statin benefit in heart failure patients who are simultaneously at risk for multiple types of events, including arrhythmias, cancer, infection, and renal failure, as well as ischemic events, Dr. Matthew Feinstein explained at the American Heart Association scientific sessions.

When he and his coinvestigators applied competing risk analysis in their meta-analysis of the randomized, placebo-controlled CORONA (N. Engl. J. Med. 2007; 357:2248-61) and GISSI-HF trials, they found after accounting for competing risks in close to 10,000 heart failure patients that those on 10 mg/day of rosuvastatin had a 17% reduction in the risk of myocardial infarction during follow-up, compared with those on placebo. This benefit fell just shy of statistical significance. However, when the researchers restricted the analysis to the nearly 7,100 subjects with ischemic heart failure, the resultant 19% reduction in MI risk with rosuvastatin did achieve significance.

While there was a consistent trend for a lower MI risk with rosuvastatin in all prespecified subgroups of patients with ischemic heart failure in the pooled analysis, this trend reached statistical significance in two subgroups: men, who were 22% less likely to have an MI on rosuvastatin than with placebo, and patients with a baseline low-density lipoprotein (LDL) cholesterol above 96 mg/dL, who had a 23% reduction in risk, reported Dr. Feinstein of Northwestern University, Chicago, and his colleagues.

"It’s likely that ischemic heart failure patients do benefit from statin therapy, contrary to current thinking, if they are likely to live long enough to derive benefit from statins in preventing atherothrombotic events," he concluded.

Session chair Dr. Lori Mosca was enthusiastic about the meta-analysis findings and their clinical implications. She also was strongly supportive of the application of competing risk analysis in this setting.

"That was actually a brilliant analysis. I really loved it. The lesson it teaches is that when we design a clinical trial where our nonischemic outcomes are more common than the ischemic outcomes that we’re trying to prevent, we really need to take a look at those competing risks. We might come to completely different conclusions if we do that," said Dr. Mosca, professor of medicine at Columbia University, New York, and director of preventive cardiology at New York-Presbyterian Hospital.

Other important take-home points from this pooled analysis of the CORONA and GISSI-HF trials are that despite all the confusion surrounding the new AHA/ACC prevention guidelines, LDL cholesterol levels still matter in terms of predicting outcomes, and that, as always, it’s important to look at gender interactions in looking at clinical trial outcomes, added Dr. Mosca, who is current chair of the AHA Expert Panel for the Effectiveness-Based Guidelines for the Prevention of Cardiovascular Disease in Women.

Noting that it’s not always possible for a physician to tell whether the cause of a patient’s heart failure is ischemic or nonischemic, she asked Dr. Feinstein if he’d prescribe a statin if he merely suspected that the heart failure was ischemic, perhaps because the patient had evidence of underlying coronary disease.

Yes, he replied, provided the patient had no contraindications to statin therapy, was able to tolerate it, and had a sufficiently long life expectancy to be able to reap the benefits. He added a caveat: Heart failure patients typically have multiple comorbid conditions that could place them at risk with higher doses of statins.

"Rosuvastatin tends to be a somewhat less toxic and better tolerated statin, and 10 mg is a relatively low dose," Dr. Feinstein noted.

The meta-analysis was conducted free of commercial sponsorship. Dr. Feinstein reported having no financial conflicts of interest.

[email protected]

DALLAS – Rosuvastatin appears to reduce the risk of acute myocardial infarction in patients with ischemic heart failure, according to a meta-analysis of two landmark statin trials.

This finding is at odds with current thinking as expressed in the new American Heart Association/American College of Cardiology (AHA/ACC) guidelines, which don’t specifically recommend statin therapy for heart failure patients because no large randomized trials have shown a significant reduction in cardiovascular events.

That’s probably because those studies relied on traditional statistical techniques of survival analysis rather than the less familiar method of competing risk analysis, which is better suited to detecting a statin benefit in heart failure patients who are simultaneously at risk for multiple types of events, including arrhythmias, cancer, infection, and renal failure, as well as ischemic events, Dr. Matthew Feinstein explained at the American Heart Association scientific sessions.

When he and his coinvestigators applied competing risk analysis in their meta-analysis of the randomized, placebo-controlled CORONA (N. Engl. J. Med. 2007; 357:2248-61) and GISSI-HF trials, they found after accounting for competing risks in close to 10,000 heart failure patients that those on 10 mg/day of rosuvastatin had a 17% reduction in the risk of myocardial infarction during follow-up, compared with those on placebo. This benefit fell just shy of statistical significance. However, when the researchers restricted the analysis to the nearly 7,100 subjects with ischemic heart failure, the resultant 19% reduction in MI risk with rosuvastatin did achieve significance.

While there was a consistent trend for a lower MI risk with rosuvastatin in all prespecified subgroups of patients with ischemic heart failure in the pooled analysis, this trend reached statistical significance in two subgroups: men, who were 22% less likely to have an MI on rosuvastatin than with placebo, and patients with a baseline low-density lipoprotein (LDL) cholesterol above 96 mg/dL, who had a 23% reduction in risk, reported Dr. Feinstein of Northwestern University, Chicago, and his colleagues.

"It’s likely that ischemic heart failure patients do benefit from statin therapy, contrary to current thinking, if they are likely to live long enough to derive benefit from statins in preventing atherothrombotic events," he concluded.

Session chair Dr. Lori Mosca was enthusiastic about the meta-analysis findings and their clinical implications. She also was strongly supportive of the application of competing risk analysis in this setting.

"That was actually a brilliant analysis. I really loved it. The lesson it teaches is that when we design a clinical trial where our nonischemic outcomes are more common than the ischemic outcomes that we’re trying to prevent, we really need to take a look at those competing risks. We might come to completely different conclusions if we do that," said Dr. Mosca, professor of medicine at Columbia University, New York, and director of preventive cardiology at New York-Presbyterian Hospital.

Other important take-home points from this pooled analysis of the CORONA and GISSI-HF trials are that despite all the confusion surrounding the new AHA/ACC prevention guidelines, LDL cholesterol levels still matter in terms of predicting outcomes, and that, as always, it’s important to look at gender interactions in looking at clinical trial outcomes, added Dr. Mosca, who is current chair of the AHA Expert Panel for the Effectiveness-Based Guidelines for the Prevention of Cardiovascular Disease in Women.

Noting that it’s not always possible for a physician to tell whether the cause of a patient’s heart failure is ischemic or nonischemic, she asked Dr. Feinstein if he’d prescribe a statin if he merely suspected that the heart failure was ischemic, perhaps because the patient had evidence of underlying coronary disease.

Yes, he replied, provided the patient had no contraindications to statin therapy, was able to tolerate it, and had a sufficiently long life expectancy to be able to reap the benefits. He added a caveat: Heart failure patients typically have multiple comorbid conditions that could place them at risk with higher doses of statins.

"Rosuvastatin tends to be a somewhat less toxic and better tolerated statin, and 10 mg is a relatively low dose," Dr. Feinstein noted.

The meta-analysis was conducted free of commercial sponsorship. Dr. Feinstein reported having no financial conflicts of interest.

[email protected]

DALLAS – Rosuvastatin appears to reduce the risk of acute myocardial infarction in patients with ischemic heart failure, according to a meta-analysis of two landmark statin trials.

This finding is at odds with current thinking as expressed in the new American Heart Association/American College of Cardiology (AHA/ACC) guidelines, which don’t specifically recommend statin therapy for heart failure patients because no large randomized trials have shown a significant reduction in cardiovascular events.

That’s probably because those studies relied on traditional statistical techniques of survival analysis rather than the less familiar method of competing risk analysis, which is better suited to detecting a statin benefit in heart failure patients who are simultaneously at risk for multiple types of events, including arrhythmias, cancer, infection, and renal failure, as well as ischemic events, Dr. Matthew Feinstein explained at the American Heart Association scientific sessions.

When he and his coinvestigators applied competing risk analysis in their meta-analysis of the randomized, placebo-controlled CORONA (N. Engl. J. Med. 2007; 357:2248-61) and GISSI-HF trials, they found after accounting for competing risks in close to 10,000 heart failure patients that those on 10 mg/day of rosuvastatin had a 17% reduction in the risk of myocardial infarction during follow-up, compared with those on placebo. This benefit fell just shy of statistical significance. However, when the researchers restricted the analysis to the nearly 7,100 subjects with ischemic heart failure, the resultant 19% reduction in MI risk with rosuvastatin did achieve significance.

While there was a consistent trend for a lower MI risk with rosuvastatin in all prespecified subgroups of patients with ischemic heart failure in the pooled analysis, this trend reached statistical significance in two subgroups: men, who were 22% less likely to have an MI on rosuvastatin than with placebo, and patients with a baseline low-density lipoprotein (LDL) cholesterol above 96 mg/dL, who had a 23% reduction in risk, reported Dr. Feinstein of Northwestern University, Chicago, and his colleagues.

"It’s likely that ischemic heart failure patients do benefit from statin therapy, contrary to current thinking, if they are likely to live long enough to derive benefit from statins in preventing atherothrombotic events," he concluded.

Session chair Dr. Lori Mosca was enthusiastic about the meta-analysis findings and their clinical implications. She also was strongly supportive of the application of competing risk analysis in this setting.

"That was actually a brilliant analysis. I really loved it. The lesson it teaches is that when we design a clinical trial where our nonischemic outcomes are more common than the ischemic outcomes that we’re trying to prevent, we really need to take a look at those competing risks. We might come to completely different conclusions if we do that," said Dr. Mosca, professor of medicine at Columbia University, New York, and director of preventive cardiology at New York-Presbyterian Hospital.

Other important take-home points from this pooled analysis of the CORONA and GISSI-HF trials are that despite all the confusion surrounding the new AHA/ACC prevention guidelines, LDL cholesterol levels still matter in terms of predicting outcomes, and that, as always, it’s important to look at gender interactions in looking at clinical trial outcomes, added Dr. Mosca, who is current chair of the AHA Expert Panel for the Effectiveness-Based Guidelines for the Prevention of Cardiovascular Disease in Women.

Noting that it’s not always possible for a physician to tell whether the cause of a patient’s heart failure is ischemic or nonischemic, she asked Dr. Feinstein if he’d prescribe a statin if he merely suspected that the heart failure was ischemic, perhaps because the patient had evidence of underlying coronary disease.

Yes, he replied, provided the patient had no contraindications to statin therapy, was able to tolerate it, and had a sufficiently long life expectancy to be able to reap the benefits. He added a caveat: Heart failure patients typically have multiple comorbid conditions that could place them at risk with higher doses of statins.

"Rosuvastatin tends to be a somewhat less toxic and better tolerated statin, and 10 mg is a relatively low dose," Dr. Feinstein noted.

The meta-analysis was conducted free of commercial sponsorship. Dr. Feinstein reported having no financial conflicts of interest.

[email protected]