Thwarted Access to PCSK9 Inhibitors Linked to Greater Risk of Major CV Events

Patients whose prescription for a PCSK9 inhibitor are rejected by payers, as well as those who eventually give up on the drugs as a treatment option due to financial frustrations, seem to face poorer cardiovascular outcomes than those who are able to take their prescribed PCSK9 inhibitor without interruption. These rocky paths are associated with increased risks of MI, ischemic stroke, and cardiac arrest, according to a new retrospective cohort analysis.

High-risk cohorts, namely people with familial hypercholesterolemia (FH) and atherosclerotic cardiovascular disease (ASCVD), had trouble accessing PCSK9 inhibitors to the same degree as lower-risk individuals.

After the US Food and Drug Administration approved evolocumab (Repatha; Amgen) and alirocumab (Praluent; Sanofi/Regeneron) for LDL cholesterol-lowering in 2015, the high price tag of these drugs—initially more than $14,000—and significant preauthorization hurdles limited access to these medications. This pressure eventually led manufacturers to cut costs by 60%, for evolocumab in October 2018 and for alirocumab in February 2019.

The new analysis, published July 23, 2019, in Circulation: Cardiovascular Quality and Outcomes, covers a period prior to that shift. Led by Kelly D. Myers, BS, chief technology officer for the FH Foundation, the research team also included physicians and individuals diagnosed with FH. It was sponsored by the FH Foundation.

Study co-author Seth J. Baum, MD (Preventive Cardiology, Inc, Boca Raton, FL), observed that prior authorization only began to affect cardiologists with the introduction of PCSK9 inhibitors, a time when rejections of these drugs were “essentially uniform.”

“So there were a lot of efforts to understand what was going on and to fix it,” Baum told TCTMD. “Very high-risk patients, like FH patients, were being denied prescriptions.” Then there were the administrative headaches for healthcare providers—Baum noted that prior authorization forms can reach 17 pages long.

Rejected Prescriptions, Abandoned Therapies

Myers and colleagues’ analysis relies upon a data set from Symphony Health that contained information on diagnosis, procedure, and prescription claims for more than 221 million people. Within this group, 161,181 patients with hypercholesterolemia were prescribed a PCSK9 inhibitor between August 2015 and December 2017.

Using propensity matching and Cox regression techniques, the study compared the trajectories of patients who maintained access to their PCSK9 inhibitor prescriptions to those individuals who abandoned their prescriptions (plausibly due to cost) or had them rejected outright.

Among the 139,036 patients on a PCSK9 inhibitor whose CV histories could be tracked over time, 4,702 (3.4%) experienced a major cardiovascular event. Risk was higher for patients whose prescriptions were rejected compared to those who had theirs paid for at least 6 months (HR 1.10; 95% CI 1.02-1.18) and those who abandoned their prescriptions compared to those who did not (HR 1.12; 95% CI 1.02-1.23).

The differences are starker when comparing people who took a PCSK9 inhibitor for at least a year with those who did not due to rejection (HR 1.16; 95% CI 1.02-1.30) or abandonment (HR 1.21; 95% CI 1.04-1.38).

Fully 63.5% of high-risk patients with diagnosed FH and ASCVD saw their prescriptions rejected. This mirrors rejections previously identified for the population at large. Women, racial minorities, and patients with less education were especially likely to have their PCSK9 inhibitor prescriptions rejected.

Seeking a Balance From All Sides

The investigators are candid about their motivations for conducting this study, writing that its “objectives were driven by the personal interest of patients affected by FH who think PCSK9 inhibitors will be life prolonging for them and have experienced denials by insurance providers.”

That said, there is broad agreement among preventive cardiologists that access to PCSK9 inhibitors has been needlessly constrained. In an editorial accompanying the paper, Khurram Nasir, MD (Yale School of Medicine, New Haven, CT), and colleagues argue: “We advocate that a mere diagnosis of FH and ASCVD should suffice approval for a PCSK9 inhibitor as long as LDL cholesterol levels remain above reasonable thresholds after guideline-directed lipid lowering therapy.”

In the current study, covering the period prior to the 2018 cholesterol guidelines that made room for non-statin therapies, “more than a quarter of patients prescribed PCSK9 inhibitors reported no use of a statin; with nearly six out of every 10 patients prescribed not reporting high-intensity statin therapy use in the last 12 months,” they point out, suggesting that simpler options had not been tried before transitioning to the more expensive drugs. Thus, the editorialists encourage the “clinical community to align prescribing practices with existing evidence-based recommendations.”

While preauthorization takes a toll on patient care, satisfaction, and outcomes, the editorial comes down on the side of balance; Nasir spoke on this same topic at the recent SCCT 2019 meeting.

“If our medical community truly aspires to overcome these blunt cost containing instruments, it is critical that clinicians are mindful of limited available resources as well as broader societal cost opportunities in our prescribing practices. Status quo is not an option anymore for parties on both sides of the aisle,” they conclude. “We are optimistic that common-sense collaboration around value-based pricing, appropriate candidate selection, maximum use of evidence-based therapies before considering PCSK9 inhibitors, streamlining, and eventual easing of prior authorization policies will alleviate suffering for stakeholder we all care the most: our patients.”

Commenting to TCTMD, Donald Lloyd-Jones, MD (Northwestern University Feinberg School of Medicine, Chicago, IL), said that while it’s impossible to account for potential confounding, the researchers did a “good job here to try to see what the effect is . . . . They do see small, but real, differences that remain even after the propensity matching to suggest that it really is important to get and take these medications for patients that are appropriate [candidates].”

Myers and Baum said they hope that this study moves the needle toward better access to PCSK9 inhibitors. “This is very much a policy issue,” Myers stated. “If one group could have the most leverage, I would think it would be somebody in government.” Baum agreed, noting that there are important messages for payers and physicians as well.