Rejection and abandonment of prescriptions for proprotein convertase subtilisin kexin type-9 inhibitors (PCSK9i) significantly increase the risk for cardiovascular (CV) events, according to a study published in Circulation: Cardiovascular Quality and Outcomes.

In this retrospective, propensity score-matched cohort study, researchers analyzed a healthcare claims dataset consisting of diagnosis, procedure, and prescription claims for patients aged ≥18 years identified with hypercholesterolemia who were prescribed ≥1 PCSK9i between August 2015 and December 2017 (n=161,181). A subset of this group also had diagnosis and procedure claims and met other inclusion criteria allowing for CV events (n=139,036).

A Cox proportional hazard regression analysis and a Stepwise Cox hazard regression analysis were performed on the post-propensity matched cohorts and the entire non-propensity matched patient cohorts, respectively. Prescription coverage was identified as paid (PD), rejected (RJ), or abandoned (AB), defined by the final adjudication status (FAS) date. Analyses specific for atherosclerotic cardiovascular disease (ASCVD) were conducted to evaluate possible differences for outcomes in patients with the highest baseline risk; these were further divided by PD, RJ, and AB patient populations. For each type of CV event, occurrences were studied by those occurring prior to FAS date and those after.

Exposure cohorts for patients prescribed a PCSK9i were 24% for PD (n=32,886), 61% for RJ (n=85,370), and 15% for AB (n=20,780). RJ status was associated with a significantly higher probability of a CV event compared with those in the PD cohort (hazard ratio [HR] 1.10; 95% CI, 1.02-1.18; P =.02), as was AB status compared with PD 1.12 (95% CI, 1.02-1.23; P =.03).

Incidence density rates (IDR) for the propensity-matched RJ and PD cohorts were 4.08 and 3.49 cases per 100 person-years, respectively (P =.02). IDR for the propensity-matched AB and PD cohorts were 3.94 and 3.44 cases per 100 person-years (P =.03), respectively.

For the ASCVD-specific analyses, the adjusted HR for freedom from the composite CV event outcome was 1.11 (95% CI, 1.02-1.22; P =.03) for RJ vs PD and 1.12 (95% CI, 0.98-1.27; P =.096) for AB vs PD.

This study is limited by unmeasured factors not accounted for in minimizing systematic differences in baseline characteristics in propensity score matching, which may also affect the generalizability of these results. Mortality is not explicitly included in this analysis because the documentation of such data is not consistently included in coding practices. Missed ASCVD diagnoses that happened outside the study period is possible due to lack of access to complete medical histories.

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The researchers suggested that access to PCSK9i has an important impact on CV outcomes in high-risk populations, and merits further analysis. Identifying and characterizing barriers to accessing PCSK9i and developing approaches to overcoming them will reduce the clinical and economic burden to patients likely to benefit from PCSK9 inhibition. This will also likely result in more cost-effective policies for payers.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Myers KD, Farboodi N, Mwamburi M, et al. Effect of Access to Prescribed PCSK9 Inhibitors on Cardiovascular Outcomes [published online July 23, 2019]. Circ Cardiovasc Qual Outcomes. doi:10.1161/CIRCOUTCOMES.118.005404