Evolocumab added to statins reduces cardiovascular events

By David Douglas

NEW YORK (Reuters Health) - Supplementing statin therapy with the PCSK9 inhibitor evolocumab (Repatha, Amgen) provides ongoing improvement in clinical outcomes, according to a secondary analysis of a large clinical trial.

"Cardiovascular patients are at a substantial risk of multiple vascular events," Sabina A. Murphy of Brigham and Women's Hospital, in Boston, told Reuters Health by email. "Taking into account total events showed that adding evolocumab to statin therapy more than doubled the number of events prevented with evolocumab compared with first events only."

Murphy and colleagues conducted a prespecified analysis of data from a randomized, double-blind, trial comparing evolocumab with placebo in more than 27,000 patients with stable atherosclerotic disease who were receiving statins.

The primary end point (PEP) was defined as time to first cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary end point was time to first cardiovascular death, myocardial infarction, or stroke.

The researchers evaluated total cardiovascular events between treatment arms over a median follow-up of 2.2 years and a maximum of 3.6 years, they report in JAMA Cardiology, online May 22.

There were 2,907 first PEP events and 4,906 total PEP events during the trial; 1,333 patients had more than one occurrence of the primary composite end point. In the initial primary analysis of the trial, 1,999 events (41%) were not analyzed.

Including both first events and subsequent events, evolocumab reduced the total PEP events by a significant 18%. There were 2,192 total primary events in the evolocumab group and 2,714 total events in the placebo group, a significant reduction.

For every 1,000 patients treated for three years, evolocumab prevented 22 first primary end point events and 52 total primary endpoint events. This was largely due to a 26% reduction in the total number of myocardial infarctions, a 23% reduction in the total number of strokes and a 22% reduction in coronary revascularizations.

These data, the researchers conclude, "provide further support for the benefit of continuing aggressive lipid-lowering therapy to prevent recurrent cardiovascular events."

Cardiologist Dr. David D. Waters, professor emeritus at the University of California, San Francisco, told Reuters Health by email, "The usual way to assess the results of treatment in a clinical trial is to report the number of patients with cardiovascular events. This is correct statistically, because each patient contributes equally to the outcome. However, events tend to cluster; that is, if you have one event you are more likely to have another subsequently compared to someone who has no event."

"As shown in this study," he added, "looking at the totality of events shows that the drug, in this case evolocumab, prevents far more events than what is suggested by the primary analysis. This finding is expected, because it was seen in previous cholesterol lowering trials (as noted by the authors) but is worthwhile documenting nonetheless."

The trial was funded by Amgen. Murphy and other authors have relationships with the company.

SOURCE: https://bit.ly/2I3ijjX

JAMA Cardiol 2019.