Effect of Access to Prescribed PCSK9 Inhibitors on Cardiovascular Outcomes

Circ Cardiovasc Qual Outcomes. 2019 Aug;12(8):e005404. doi: 10.1161/CIRCOUTCOMES.118.005404. Epub 2019 Jul 23.

Abstract

Background: Atherosclerotic cardiovascular disease remains a major cause of death and disability, especially for high-risk familial hypercholesterolemia individuals. PCSK9i (proprotein convertase subtilisin kexin type 9 inhibitors) reduce low-density lipoprotein cholesterol levels and cardiovascular event rates. However, PCSK9i prescriptions are rejected at high rates by payers, and use is often delayed or eventually abandoned as a treatment option. We tested the hypothesis that acute coronary syndromes, coronary interventions, stroke, and cardiac arrest are more prevalent in patients with rejected or abandoned PCSK9i prescriptions than for those with paid PCSK9i prescriptions.

Methods and results: We identified 139 036 individuals aged ≥18 years who met the following 3 criteria: prescribed PCSK9i between August 2015 and December 2017, had claims history, and had an established date of exposure for paid, rejected, or abandoned status. To compare the effects of rejected versus paid and abandoned versus paid status, propensity score matching was performed to minimize confounding because of baseline differences in patient groups. Cox regression analyses and incidence density rates for cardiovascular events were estimated on the propensity score-matched cohorts. Patients who received 168 or more days of paid PCSK9i medication within a 12-month period were defined as paid. The hazard ratios for composite cardiovascular events outcome in propensity score-matched analyses were 1.10 (95% CI, 1.01-1.19; P=0.02) for rejected versus paid and 1.12 (95% CI, 1.01-1.24; P=0.03) for abandoned versus paid. In a stricter analysis where paid patients were defined by receiving 338 or more days of therapy within 12-months, hazard ratio was 1.16 (95% CI, 1.02-1.30; P=0.04) for rejected versus paid and 1.21 (95% CI, 1.04-1.38; P=0.03) for the abandoned versus paid status. Higher PCSK9i rejection rates were observed with women, racial minorities, and lower-income groups.

Conclusions: Individuals in the rejected and abandoned cohorts had significantly increased risk of cardiovascular events compared with those in the paid cohort. Rejection, abandonment, and disparities related to PCSK9i prescriptions are related to higher cardiovascular outcome rates.

Keywords: cause of death; hypercholesterolemia; insurance; myocardial infarction; statins.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anticholesteremic Agents / adverse effects
  • Anticholesteremic Agents / therapeutic use*
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / prevention & control*
  • Databases, Factual
  • Drug Prescriptions
  • Female
  • Health Services Accessibility*
  • Humans
  • Hypercholesterolemia / diagnosis
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / epidemiology
  • Male
  • Middle Aged
  • PCSK9 Inhibitors*
  • Practice Patterns, Physicians'*
  • Prevalence
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Serine Proteinase Inhibitors / adverse effects
  • Serine Proteinase Inhibitors / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • United States / epidemiology

Substances

  • Anticholesteremic Agents
  • PCSK9 Inhibitors
  • Serine Proteinase Inhibitors
  • PCSK9 protein, human