Abstract 19342: The Impact of PCSK9 Inhibitors on Lipid Levels and Outcomes in Patients With Primary Hypercholesterolemia: A Network Meta-analysis
Introduction: We performed a network meta-analysis of randomized controlled trials (RCTs) in patients with primary hypercholesterolemia to compare the impact of PCSK9 inhibitors with placebo and ezetimibe on lipid levels and outcomes.
Hypothesis: PCSK9 inhibitors will significantly lower LDL-C greater than ezetimibe and improve outcomes.
Methods: MEDLINE/PubMed, Cochrane CENTRAL, and ClinicalTrials.gov were searched for RCTs assessing PCSK9 inhibitors versus other therapies in patients with primary hypercholesterolemia. Mixed treatment comparison model generation was performed to directly and indirectly compare PCSK9 inhibition on lipid levels with ezetimibe and placebo. Odds ratios with 95% confidence intervals (OR [95% CIs]) were generated with random-effect models to compare outcomes.
Results: Our meta-analysis included 17 RCTs with 13,083 patients that were randomized to PCSK9 inhibitors (n=8,250), placebo (n=3,957), ezetimibe (n=846), or PCSK9 inhibitors and ezetimibe (n=30). The mean age was 59±10, 52% were male, 34% had coronary artery disease, 51% had hypertension, 19% had diabetes mellitus, baseline LDL of 122±36 mg/dL, total cholesterol of 199±39 mg/dL, and HDL of 51±14 mg/dL. PCSK9 inhibitors significantly reduced LDL cholesterol by 57% relative to placebo (p<0.001) and 36.1% relative to ezetimibe (p<0.001). PCSK9 inhibitors reduced the incidence of all-cause mortality (OR 0.43 [95% CI 0.22-0.82], p=0.01) with a trend for cardiovascular death (OR 0.50 [95% CI 0.22-1.13], p=0.10) and cardiovascular events (OR 0.67 [95% CI 0.43-1.04], p=0.07) when compared with placebo.
Conclusions: PCSK9 inhibition significantly improved lipid profiles and reduced the incidence of all-cause mortality compared with placebo. Thus, PCSK9 inhibitor therapy, once approved, may serve as an excellent alternative for patients with statin intolerance and for those who do not respond to conventional lipid reduction therapy.
Author Disclosures: M.J. Lipinski: None. R.O. Escarcega: None. T. Lhermusier: None. N.C. Baker: None. R. Torguson: None. H. Brewer: None. R. Waksman: None.
- © 2015 by American Heart Association, Inc.