Lack of access to PCSK9 inhibitors associated with cardiovascular events

Patients who are prescribed PCSK9 inhibitors but do not receive them may be at higher risk for cardiovascular events than patients with paid PCSK9 prescriptions, according to a new study.

Researchers used a health care claims data set to identify adults who had been prescribed a PCSK9 inhibitor between August 2015 and December 2017, who had a claims history, and who had a date established for paid, rejected, or abandoned status of their PCSK9 inhibitor prescription. Patients were considered to be in the paid group if they received at least 168 days of a paid PCSK9 inhibitor in a 12-month period; patients in the abandoned group were approved for coverage but did not fill the prescription. The main study outcome was the earliest diagnosis of myocardial infarction, unstable angina, acute ischemic heart disease, ischemic stroke, percutaneous coronary intervention, coronary artery bypass graft, or cardiac arrest after the date of final adjudication for a PCSK9 inhibitor prescription.

The study was funded by the FH Foundation, a nonprofit organization focused on research, education, and advocacy regarding familial hypercholesterolemia. Of the nine study authors, three are employees of the foundation, four are paid consultants, and two are unpaid consultants. Results of the study were published by Circulation: Cardiovascular Quality and Outcomes on July 23.

Overall, 139,036 patients were included in the study. The average age was 66 years, 51% were women, and 63% were white. The paid prescription group included 32,886 patients (24%), the rejected group included 85,370 patients (61%), and the abandoned group included 20,780 patients (15%). Overall, 4,702 patients who were prescribed a PCSK9 inhibitor (3.4%) experienced a composite cardiovascular event. In propensity score-matched analyses, hazard ratios for the composite outcome were 1.10 (95% CI, 1.01 to 1.19; P=0.02) for rejected claims versus paid claims and 1.12 (95% CI, 1.01 to 1.24; P=0.03) for abandoned versus paid claims. When the researchers used a narrower definition of paid status (receiving at least 338 days of therapy in a 12-month period), the corresponding hazard ratios were 1.16 (95% CI, 1.02 to 1.30; P=0.04) and 1.21 (95% CI, 1.04 to 1.38; P=0.03), respectively. Rejection rates for payment of a PCSK9 inhibitor prescription were higher in women, minorities, and those of lower income.

The researchers noted that their results could have been affected by residual confounding and that some patients could have received samples of PCSK9 inhibitors from their clinicians, among other limitations. They also acknowledged their bias in favor of PCSK9 inhibitor use in patients with familial hypercholesterolemia. However, they concluded that their study demonstrates the real-world impact of access to PCSK9 inhibitors on prevention of atherosclerotic cardiovascular disease events in high-risk patients. They called for the establishment of large registries to help characterize factors affecting access, such as disparities, health care use, and cost and reimbursement burden. “Appropriately identifying and characterizing barriers to PCSK9 [inhibitor] 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,” they wrote.

The authors of an accompanying editorial noted that almost four prescriptions for PCSK9 inhibitors are initially denied for every five that are approved, according to previous research, and called the high rejection rates regardless of baseline risk in the current study disappointing. The editorialists said that a diagnosis of familial hypercholesterolemia and atherosclerotic cardiovascular disease should be enough to approve a prescription for a PCSK9 inhibitor, as long as LDL cholesterol levels are above reasonable thresholds after guideline-directed lipid-lowering therapy. “Easing restrictions for this high-risk population will not only bode well for mending existing distrust between clinicians and payers but likely be a cost-effective approach leading to better cardiovascular outcomes,” they wrote.

The editorialists also addressed the high abandonment rate of PCSK9 inhibitor prescriptions, nearly one in six, among patients who were approved to receive the drug, noting that the average out-of-pocket cost in this group would have been over $233 per month. “These finding[s] remind us that merely improving the [prior authorization] process will not suffice,” the editorialists wrote. In addition, they encouraged clinicians to align their prescribing practices with existing evidence-based recommendations. Before a PCSK9 inhibitor is prescribed for statin-associated side effects in high-risk patients, side effects should be documented to at least two different statins, one at the lowest therapeutic daily dose, they recommended.