In patients with heterozygous familial hypercholesterolemia and/or cardiovascular disease, alirocumab and evolocumab reduced LDL cholesterol by 54% to 63% at 24 weeks.
Cohort (n=72)
Open-label
No
Do alirocumab and evolocumab reduce LDL cholesterol and calculated 10-year cardiovascular risk in patients with HeFH and/or CVD on maximal tolerated cholesterol lowering therapy?
Effect estimate: 54% to 63% reduction
p-value: p=<0.0001
BACKGROUND: Efficacy and safety of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, alirocumab (ALI) and evolocumab (EVO) have previously been evaluated through controlled clinical trials with selective patient groups. Post-commercially, in patients with heterozygous familial hypercholesterolemia (HeFH) and/or cardiovascular disease (CVD) with suboptimal LDL cholesterol (LDLC) lowering on maximal tolerated cholesterol lowering therapy, we assessed efficacy and safety of ALI and EVO. METHODS: Post-commercially, we started 25 patients on ALI 75 mg, 15 on ALI 150 mg, and 32 on EVO 140 mg bi-weekly added to entry LDLC lowering regimen, with follow-up for a median 24 weeks. History, physical exam, demographics, and adverse event data were collected. Changes in LDLC and AHA and NIH calculated 10-year CVD risks were assessed on ALI and EVO. RESULTS: Of 72 patients, 25 had HeFH only, 25 CVD only, 22 had both, median age was 65 years, 63% females, 38% males, 86% Caucasian, 11% African-Americans, 17% diabetics, 63% on anti-hypertensives, and 7% smokers. At entry, 30 (42%) were on a statin and 42 (58%) could not tolerate any statins. At 24-weeks, median LDLC decreased on ALI 75 mg from 117 to 62 mg/dL (-54%), on ALI 150 mg from 175 to 57 mg/dL (-63%), and on EVO 140 mg from 165 to 69 mg/dL (-63%), p .05) between ALI 150 and EVO 140 mg, but were less on ALI 75 mg vs ALI 150 mg and EVO 140 mg (p <.05). Percent reductions in 10-year CVD risks by AHA and NIH calculators, respectively were ALI 75 mg -22 and -44%, ALI 150 mg -31 and -50%, and EVO 140 mg -29 and -56%, p ≤.002 for all. The three most common adverse events included flu-like myositis 10%, respiratory tract symptoms 8%, and injection site reaction 6%. CONCLUSION: In patients with HeFH and/or CVD, LDLC was lowered by 63% on EVO and ALI 150 mg, and 54% on ALI 75 mg. Adverse events were minimal and tolerable. ALI and EVO represent paradigm shifts in LDLC lowering. Long term, post-commercial safety and efficacy remain to be determined.
Shah et al. (Mon,) conducted a cohort in Heterozygous familial hypercholesterolemia (HeFH) and/or cardiovascular disease (CVD) (n=72). Alirocumab and Evolocumab vs. Baseline was evaluated on Change in LDL cholesterol at 24 weeks (54% to 63% reduction, p=<0.0001). In patients with heterozygous familial hypercholesterolemia and/or cardiovascular disease, alirocumab and evolocumab reduced LDL cholesterol by 54% to 63% at 24 weeks.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: