Abstract 23073: Cardiovascular Efficacy of PCSK9 Inhibition Among 1,578 Patients With Familial Hypercholesterolemia: The SPIRE Clinical Trials FH Analysis

Abstract

Background: Familial hypercholesterolemia (FH) is a genetic disorder with elevations of low-density lipoprotein cholesterol (LDLC) and premature atherosclerotic events. Therapeutic monoclonal antibodies that inhibit proprotein convertase subtilisin-kexin type 9 (PCSK9) are indicated for the reduction of LDLC in patients with FH, but placebo-controlled outcome data for FH patients are not available. Objective: To estimate the efficacy of PCSK9 inhibition with bococizumab on future cardiovascular events among FH and non-FH patients enrolled in the four 1-year SPIRE Lipid Lowering trials or in the two cardiovascular outcomes trials (SPIRE-1 and SPIRE-2). Design, Setting, and Participants: Six multinational, randomized, placebo-controlled trials inclusive of 1,578 patients with FH (molecular analysis or Simon Broome criteria) and 15,959 patients without FH and levels of LDLC ≥100 mg/dL or non-HDLC ≥130 mg/dL at trial entry. Intervention: Bococizumab 150 mg SC every 2 weeks or matching placebo. The median follow-up period was 49 weeks. Main Outcomes and Measures: Incident major adverse cardiovascular events (MACE) including nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Results: Among FH patients, MACE occurred in 18 allocated to bococizumab and 22 to placebo (hazard ratio [HR]=0.83; 95% confidence interval [CI] 0.44-1.54, P=0.55). In the subgroup of 620 FH patients with LDLC ≥160 mg/dL, MACE occurred in 9 allocated to bococizumab and 13 to placebo (HR=0.74; 95% CI 0.31-1.75, P=0.49). For the 1,065 FH patients specifically enrolled in SPIRE-1 or SPIRE-2, MACE occurred in 11 allocated to bococizumab and 18 allocated to placebo (HR=0.64, 95% CI 0.30-1.35, P=0.24). These effect estimates are similar in magnitude to that observed in the 15,959 patients without FH (HR=0.79, 95% CI 0.64-0.97, P=0.023). Conclusions and Relevance: Statin-treated FH patients given the PCSK9 inhibitor bococizumab have a similar magnitude of risk reduction for hard cardiovascular events as do patients without FH. These data have importance for clinical practice and guidelines for cardiovascular disease prevention. Trial Registration: ClinicalTrials.gov: NCT01968954, NCT01968967, NCT02100514, NCT01968980, NCT01975376, NCT01975389