Efficacy and safety of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, alirocumab and evolocumab, a post-commercialization study

Abstract

BackgroundEfficacy-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 69 patients with heterozygous familial hypercholesterolemia (HeFH) and/or cardiovascular disease (CVD) with suboptimal LDL cholesterol (LDLC) lowering on maximal tolerated LDLC therapy, we assessed efficacy and safety of ALI and EVO.MethodsPost-commercially, we started 29 patients on ALI 75 mg, 18 on ALI 150 mg, and 22 on EVO 140 mg every 2 weeks added to a maximally tolerated LDLC-lowering regimen. Since LDLC lowering did not differ between ALI 150 and EVO 140 mg, ALI 150-EVO 140 data were pooled (ALI-EVO). Changes in LDLC and AHA and NIH calculated 10-year CVD risks were assessed.ResultsOf the 69 patients, 25 had HeFH, 25 CVD, and 19 had both. At entry, 23 (33%) took statins and 46 (67%) were statin-intolerant. Mean ± SD and median follow-up were 49 ± 13 and 49 weeks on ALI 75 mg, and 37 ± 12 and 33 weeks on ALI-EVO. In the ALI-EVO group (n = 40), median LDLC fell from 165 mg/dl at entry to 70 mg/dl (median − 59%, p < .0001). AHA 10-year calculated CVD risk fell from 10.2 to 5.5% (median − 28%, p < .0001), and by the NIH calculator from 14.2 to 3.6% (median − 78%, p < .0001). In the ALI 75 mg group (n = 29), entry LDLC fell from 115 to 68 mg/dl (median − 39%, p < .0001). AHA 10-year calculated CVD risk fell from 11.5 to 7.3% (median − 20%, p = .004), and NIH 10-year risk from 12.9 to 5.1% (median 67%, p < .0001). Absolute and percent change in LDLC was independent of statin use. There were flu-like symptoms in 14% of patients. Adverse events did not differ (p > 0.05) between ALI 75 mg and ALI-EVO.ConclusionIn patients with HeFH and/or CVD, LDLC decreased from 115 to 68 mg/dl (39%) on ALI 75 mg with mean follow-up of 49 weeks, and from 165 to 70 mg/dl (59%) on ALI-EVO over 37 weeks, p < .0001 for both. Adverse events were minimal and tolerable. ALI and EVO represent paradigm shifts in LDLC lowering.

Adverse Events Associated With PCSK9 Inhibitors: A Real‐World Experience

“…Five studies published data of AEs associated with PCSK9 inhibitors in a limited number of patients. [19][20][21][22][23] These previous studies described a similar set of AEs associated with PCSK9 inhibitors in 15-39% of the patients. The method of acquisition of AEs was often not described in detail.…”

“…Although meta‐analyses of published RCTs showed no significant difference in (serious) AE occurrence between patients receiving PCSK9 inhibitors and control, real‐world data are limited. Five studies published data of AEs associated with PCSK9 inhibitors in a limited number of patients . These previous studies described a similar set of AEs associated with PCSK9 inhibitors in 15–39% of the patients.…”

PCSK9 Inhibitors: Clinical Relevance, Molecular Mechanisms, and Safety in Clinical Practice

“…It is estimated that 24 million patients in the U.S. alone could be eligible for PCSK9i therapy. 21 Although there are no such data for the Brazilian population, the efficacy and safety of these agents have been recognized by regulatory agencies in the country, and two PCSK9i have been approved by the National Health Surveillance Agency (ANVISA) and are commercially available: Praluent® (alirocumab) and Repatha™ (evolocumab). 22 Their approved indications for use in Brazil, as well as dosages and the magnitude of LDL reduction achieved, are summarized in table 1.…”