Applied Evidence

Newer cholesterol-lowering agents: What you must know

J Fam Pract. 2018 June;67(6):339-341,344-345

From The Journal of Family Practice | 2018;67(6):339-341,344-345.

References

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PCSK9 inhibitors reduce adverse CVD events when added to a statin. In a study designed to evaluate AEs and LDL-C lowering with evolocumab, a prespecified exploratory outcome was the incidence of adjudicated CVD events. After one year of therapy, the rate of events was reduced from 2.18% in the standard-therapy group to 0.95% in the evolocumab group—a relative decrease of 53%, but an absolute decrease of 1.23% (NNT=81).¹⁷

A similar reduction in the rate of major adverse CVD events was found in adding alirocumab to ongoing statin therapy. In a post hoc analysis of patients who received either adjunctive alirocumab or placebo, CVD events (death from coronary heart disease, nonfatal myocardial infarction [MI], fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization) were 1.7% vs 3.3% (hazard ratio=0.52; 95% confidence interval, 0.31-0.90).¹¹

FOURIER, the first major trial designed to evaluate cardiovascular outcomes with PCSK9 therapy, showed that adding evolocumab to effective statin therapy reduced the average LDL-C level from 92 mg/dL to 30 mg/dL.¹² Evolocumab decreased the composite CVD outcome (cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization) over 2.2 years from 11.3% to 9.8%—a 15% RRR and a 1.5% ARR (NNT=67). Most of the participants were receiving high-intensity statin therapy at study entry. AEs were similar between the study groups.¹²

A prespecified analysis of FOURIER data found that evolocumab did not increase the risk of new-onset diabetes in patients without diabetes or prediabetes at baseline. Fasting plasma glucose and hemoglobin A1c levels in the evolocumab and placebo groups remained similar throughout the trial in patients with diabetes, prediabetes, or normoglycemia.¹⁸ Additionally, a randomized trial involving patients who received either evolocumab or placebo in addition to statin therapy found no significant difference in cognitive function between the groups over a median of 19 months.¹⁹

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