Ridker PM, et al. - The efficacy of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibition via bococizumab, compared to placebo, on hard cardiovascular outcomes (major adverse cardiovascular events: nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) was assessed in familial hypercholesterolemia (FH) patients enrolled in the SPIRE (Studies of PCSK9 Inhibition and the Reduction of vascular Events) program. Patients with and without FH who were selected for comparable lipid levels (on-statin levels of low-density lipoprotein cholesterol (LDL-C) >100 mg/dL or non-HDLC > 130 mg/dL) were randomized to bococizumab 150 mg SC every 2 weeks or to matching placebo. A similar magnitude of bococizumab-induced risk reduction for hard cardiovascular events was noted in the subgroup of statin-treated FH patients as was seen in those without FH, with no evidence of statistical heterogeneity between groups.

• Among 1,578 FH patients and 15,959 patients without FH who were selected for comparable lipid levels (on-statin levels of LDL-C >100 mg/dL or non-HDLC > 130 mg/dL), the efficacy of PCSK9 inhibition with bococizumab on future cardiovascular event rates was assessed.
• Computer generated codes were used to randomize all patients to bococizumab 150 mg SC every 2 weeks or to matching placebo in the SPIRE (Studies of PCSK9 Inhibition and the Reduction of vascular Events) clinical trials program.
• All patients were followed over a median period of 11.2 months for major adverse cardiovascular events (MACE, nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death).
• Analysis was by intention to treat.

• Data showed that when compared with FH non-FH patients, patients enrolled in the SPIRE trials were on average younger (58 vs 63 yrs), more likely to be women (42 vs 35%), more likely to be primary prevention patients (42 vs 23%), had higher mean baseline LDL-C levels (151 vs 127 mg/dL), and lower rates of diabetes (25 vs 52%), and hypertension (59 vs 82%).
• Bococizumab caused 55% reductions in LDL-C both in FH and non-FH patients.
• Occurrence of MACE was reported among 18 of 781 allocated to bococizumab and 22 of 797 allocated to placebo (HR 0.83; 95% CI 0.44-1.54, P=0.55).
• As per findings, this best estimate of effect was similar in magnitude to that observed in the much larger group of patients without FH (HR 0.79, 95%CI 0.64-0.97, P=0.023) with no statistically significant evidence of heterogeneity between groups (P=0.87).
• Among those with and without FH, similar incidence rate ratios comparing bococizumab to placebo for adverse events were noted.
• Among those with FH vs those without FH, higher proportion of patients developed anti-drug antibodies (43% versus 36%, P < 0.001).