PCSK9 inhibitors safe, effective in Asian patients, but expensive to use

PCSK9 inhibitors alirocumab and evolocumab are not only safe and well tolerated but also efficacious in Asian patients, results of a real-world study in Singapore have shown. However, about a third of patients stopped using these medications due to their high costs.

“In our study, the majority of our patients were self-paying, and we found that high medication costs adversely influenced patient adherence,” the researchers said.

“Similar to other countries, high medication costs were associated with poor adherence of PCSK9 inhibitors and had great impact on medication persistence,” they added. [JAMA Cardiol 2017;2:1217-1225; J Clin Lipidol 2019;13:725-734; J Geriatr Cardiol 2021;18:261-270]

This retrospective review was conducted in a tertiary cardiology centre for patients newly initiated on PCSK9 inhibitors between 1 June 2017 and 31 July 2021. Those aged at least 21 years with a minimum 1-month follow-up were eligible.

The researchers compared adverse drug reactions (ADRs), drug discontinuation, adherence patterns, and efficacy between evolocumab and alirocumab groups. They also assessed the outcomes through multivariable and propensity score-adjusted Cox regression analyses.

Eighty-seven patients were screened, of whom 80 met the eligibility criteria (51 for evolocumab and 20 for alirocumab). [Proc Singap Healthc 2022;doi:10.1177/20101058221144115]

No significant between-group differences were seen in ADRs (11.8 percent vs 3.4 percent; multivariable analysis: adjusted hazard ratio [aHR], 2.97, 95 percent confidence interval [CI], 0.34‒25.89; after propensity score adjustment: aHR, 3.24, 95 percent CI, 0.38‒27.69) and discontinuation rates (27.5 percent vs 34.5 percent; multivariable analysis: aHR, 0.89, 95 percent CI, 0.40‒2.02; after propensity score adjustment: aHR, 0.88, 95 percent CI, 0.39‒1.99).

The main reason for treatment discontinuation was high medication cost. One-third of patients did not adhere to PCSK9 inhibitor treatment. Of note, both groups demonstrated significant reduction in low-density lipoprotein cholesterol relative to baseline levels.

“PCSK9 inhibitors were efficacious, safe, and well-tolerated in our study,” the researchers said. “These findings are consistent with those observed in outcome trials, real-world studies, and meta-analyses. [N Engl J Med 2017;376:1713-1722; Clin Pharmacol Ther 2019;105:496-504; Ther Clin Risk Manag 2017;13:957-965; Circ Rep 2019;1:219-227]

Most ADRs reported by participants were nonspecific, such as gastrointestinal side effects and dizziness. The association with PCSK9 inhibitor use was temporal, and the researchers could not infer causation.

High treatment cost

Discontinuation rates in the present study (34.5 percent in alirocumab and 27.5 percent in evolocumab) were higher than for those in earlier randomized controlled trials (14.2 percent and 12.5 percent for alirocumab and evolocumab, respectively). This could be attributed to the patients’ perception of high medication costs (20.7 percent in alirocumab and 9.8 percent in evolocumab; p=0.193).

This finding was supported by another real-world study, which also reported a high discontinuation rate (33.3 percent) of PCSK9 inhibitors at 60 days. [Ther Clin Risk Manag 2017;13:957-965]

“Given that PCSK9 inhibitors have been proven to reduce cardiovascular events in randomized controlled trials, further studies are warranted to examine the cost-effectiveness of PCSK9 inhibitors to rationalize sustainable use of this efficacious but expensive therapeutic class of drugs for cardiovascular prevention,” the researchers said.