Muscle-Related Adverse Events Associated With PCSK9 Inhibitors in a Veteran Population.

Background: Statins and PCSK9 inhibitors (PCSK9i) are used to lower low-density lipoprotein cholesterol and reduce cardiovascular events, yet some patients are unable to tolerate statin therapy due to muscle-related adverse events (AEs). The effect of PCSK9i on muscle-related AEs is not well studied, and available data show inconsistent incidence rates.

Methods: The primary study outcome was to determine the percentage of patients who developed muscle-related PCSK9i AEs. A secondary outcome was to analyze data based on 4 subgroups: tolerated a full PCSK9i dose; tolerated alternative PCSK9i following initial intolerance; required a PCSK9i dose reduction, or discontinued PCSK9i. In addition, the percentage of statin- and/or ezetimibe-intolerant patients in these 4 groups was determined. Another secondary outcome was the management strategies taken for patients who were on a reduced (monthly) dose of PCSK9i who did not reach their low-density lipoprotein cholesterol goal. Statin intolerance was defined as intolerable skeletal muscle AEs on at least 3 different statins. We conducted a single-center, retrospective review of patients prescribed a PCSK9i between December 1, 2017, and September 1, 2021, at a patient aligned care team clinic at the Wilkes-Barre Veterans Affairs Medical Center.

Results: The study included 137 veterans. Twenty-four patients (17.5%) developed a muscle-related AE while on a PCSK9i. In predefined subgroups studied, statin intolerance ranged from 68.1% to 100%, ezetimibe intolerance ranged from 41.6% to 83.3%, and both statin and ezetimibe intolerance ranged from 36.3% to 83.3%.

Conclusions: In this study, muscle-related PCSK9i AEs occurred at a similar incidence rate to that reported in previous clinical trials and exceeded the incidence rate reported in the prescribing information for alirocumab and evolocumab. It also appears that patients who have a prior muscle-related intolerance to a statin and/or ezetimibe have a higher likelihood of developing a muscle-related AE to a PCSK9i.