Rejected, Unfilled PCSK9 Inhibitor Prescriptions Linked to Higher Risk of Cardiovascular Events

New study findings indicate that patients face a higher risk of cardiovascular events, such as myocardial infarction and stroke, if their insurer will not cover an expensive therapy to lower their cholesterol or if they do not fill their prescription.

Insurers frequently denied coverage for the therapeutic class, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), in the years after they were approved in 2015. Now, research published in Circulation: Cardiovascular Quality and Outcomes, found that patients were 16% more likely to have a cardiovascular event if their prescription was rejected than if their prescription was covered and filled for approximately 1 year. If a prescription was covered but a patient failed to fill it, the patients were 21% more likely to have a cardiovascular event.

Incidence death rates (IDRs) were 3.52 vs 2.93 per 100 person-years for those who had their prescriptions rejected compared with those who filled and paid for their prescriptions, respectively. IDRs were 3.37 vs 2.79 per 100 person-years for those who did not fill their prescriptions compared with those who filled and paid for their prescriptions, respectively.

The FDA approved alirocumab (Praluent) and evolocumab (Repatha) a month apart for the treatment of elevated low-density lipoprotein (LDL) cholesterol in patients with familial hypercholesterolemia (FH) or clinical atherosclerotic disease (ASCVD), who are considered at high risk for cardiovascular events. When the 2 drugs hit the market, they came with an annual price of $14,000. The drugs have since seen price cuts, now coming with an annual cost of $5850.

At the time of the study, the drugs still came with a $14,000 price tag, and study findings revealed that insurers rejected about two-thirds (63.5%) of prescriptions for patients with either ACSVD or FH. There was an overall rejection rate of 61% among the 139,036 patients included in the study, who were at least 18 years old and were prescribed PCSK9i between August 2015, the month the second drug was approved, and December 2017. Women, blacks, and Hispanics were more likely to have their prescriptions rejected.

Meanwhile, 15% of patients did not fill their prescriptions and 24% of patients filled and paid for their prescription. A total of 88,770 (63.8%) patients had a history of ACSVD, and 2889 (2.1%) had a history of FH, of which 1944 also had a history of ACSVD.

Cardiologists had high hopes for the PCSK9i class after phase 3 studies showed they could reduce LDL cholesterol by as much as 60%. By the time investigators reported results for evolocumab's cardiovascular outcomes trial in 2017, however, cardiologists complained bitterly that payers were turning down claims for patients who met the criteria for the drug, even those with FH who could not reduce their LDL cholesterol with a high-intensity statin. Payers, meanwhile, said that many physician offices were not completing the required documentation to ensure that only those patients who absolutely needed the drug would gain access.

According to researchers for the current study, the rate of unfilled prescriptions could have been driven by high co-payments, with the abandoned prescriptions averaging $233.30. This rate was $100 higher than prescriptions that were covered. Approximately 65% of the unfilled prescriptions were from Medicare beneficiaries, with the researchers noting that CMS does not allow for copay assistance for Medicare Part D prescriptions, which often leads to higher out-of-pocket costs.

“We have both treatment guidelines and available medication to help reduce cholesterol and associated cardiovascular events in the most vulnerable high-risk patients, and yet barriers in the healthcare system—such as higher treatment costs, tight restrictions of approvals, Medicare rules against co-payment assistant, and lack of coverage—are delaying treatment,” said Kelly D. Myers, BS, chief technology officer for The FH Foundation, and lead author of the study, in a statement.

This finding matches research published in this month’s issue of The American Journal of Managed Care^®, in which researchers found that capping patient assistance for specialty prescription drugs led to significantly lower monthly fill rates, higher risk of discontinuation, and lower proportion of days covered.