Patients whose prescription for PCSK9 inhibitors (proprotein convertase subtilisin kexin type 9 inhibitors) are either unfilled or rejected by insurance companies have a higher rate of cardiovascular events than those whose prescriptions are paid for. Kelly D Myers (The FH Foundation, Pasadena, USA), et al also found that high co-payments may make patients less likely to fill prescriptions, even when insurers approve them, and that prescriptions written for women, blacks and Hispanics were more likely to be rejected by companies. The study was published in Circulation: Cardiovascular Quality and Outcomes.
The authors write: “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.”
PCSK9 inhibitors act by reducing low-density lipoprotein cholesterol levels and cardiovascular event rates. But the drugs were expensive initially, with prescriptions rejected at high rates by payers, and their use is often delayed or abandoned. Myers et al tested the hypothesis that acute coronary syndromes, coronary interventions, stroke, and cardiac arrest are more prevalent in patients with rejected or abandoned PCSK9 inhibitor prescriptions than in for those with paid prescriptions.
Myers and colleagues used anonymised data from a healthcare claims dataset to identify 139,036 patients aged ≥18 years who had been prescribed PCSK9 inhibitors between August 2015 and December 2017, had a claims history, and had an established date of exposure for paid, rejected, or abandoned status. To minimise confounding due to baseline differences in subject groups, investigators performed propensity score matching and compared the effects of rejected versus paid and abandoned versus paid status. Patients who received ≥168 days of paid PCSK9 inhibitor medication within a 12-month period were defined as paid. Cox regression analyses and incidence density rates for cardiovascular events were estimated on the propensity score-matched cohorts.
Hazard ratios (HR) for composite cardiovascular events outcome in propensity score-matched analyses were 1.1 (95% confidence interval (CI) 1.01–1.19, p =0.02) for rejected versus paid prescriptions, and 1.12 (95% CI 1.01–1.24, p=0.03) for abandoned versus paid prescriptions. A further analysis in which paid patients were defined as receiving ≥338 days of treatments within a 12 month period, HR was 1.16 (95% CI 1.02–1.30, p=0.04) for rejected versus paid prescriptions, and 1.21 (95% CI, 1.04–1.38, p=0.03) for abandoned versus paid prescriptions. In addition, researchers found higher rejection rates for PCSK9 inhibitor prescriptions with women, racial minorities, and lower-income groups.
The authors also noted that those with both familial hypercholesterolaemia (FH) and previous atherosclerotic cardiovascular disease (ASCVD) had the highest risk of events—with a markedly increased risk of cardiovascular events compared to those without the conditions—but were denied access to the drugs to a similar extent. The study found a HR of 2.8 (95% CI 1.78–4.42, p<0.001) for the FH cohort versus individuals who did not have a documented diagnosis of FH or pre-final adjudication status (FAS) ASCVD; 2.12 (95% CI 1.86–2.43, p<0.001) for ASCVD versus non-FH and non-ASCVD; 1.75 (95% CI 1.48–2.08, p<0.001) for FH plus ASCVD versus ASCVD alone; and 5.4 (95% CI 4.28–6.9, p<0.001) for FH plus ASCVD versus non-FH and non-ASCVD. In addition, there was no statistical difference in risk between primary prevention FH and secondary prevention ASCVD.
“Individuals with FH and ASCVD face an extremely high risk of cardiovascular events and are more likely to have heart attacks and serious cardiovascular events if they are rejected or abandon their prescription. Alarmingly two-thirds of their prescriptions were rejected in this study,” Myers told Cardiovascular News. “It is critical that individuals with FH are identified, and comprehensive therapy is initiated early in life.”
The authors recommend that prospective data that is specific for patients who would benefit from the therapy be collected, such as in the current CASCADE FH Registry, in order to understand the long-term effects of the drugs, as well as any potential challenges. They also suggest that the health disparities for sex, race, education and income that they noted in their study be examined and addressed.
Myers et al write: “Establishment and use of large registries, including patients prescribed PCSK9is [PCSK9 inhibitors], may, in the long run, provide valuable insights and the ability to accurately characterise associated social determinants of disparities, healthcare use, cost and reimbursement burden, impact on comorbidities, and all-cause and cardiovascular mortality. Appropriately identifying and characterising barriers to PCSK9i access, and developing approaches to overcome them, will reduce the clinical and economic burden for patients who are likely to benefit from PCSK9 inhibition and likely result in more cost-effective policies for payers.”
In an accompanying editorial, Khurram Nasir (Yale School of Medicine, and Center for Outcomes Research and Evaluation, Yale New Haven Health, Connecticut, USA) et al comment: “As the market forces have led to significant reduction in PCSK9i prices, we think that the cardiovascular community is right to question these persistent obstacles in providing the right care for the right patient. In its current form, there are clear unintended consequences of PA [prior authorisation, a utilisation management policy] that are not only having a toll on patient care and satisfaction but possibly on preventable outcomes as underscored by Myers et al. We are optimistic that common-sense collaboration around value-based pricing, appropriate candidate selection, maximum use of evidence-based therapies before considering PCSK9i, streamlining, and eventual easing of PA policies will alleviate suffering for stakeholder we all care the most: our patients.”