Efforts to Up PCSK9 Use Still Falling Short, Analysis Finds

Although some of the barriers that have kept cholesterol-lowering PCSK9 inhibitors out of reach for many patients in the United States have eased a bit in recent years, a new analysis suggests that insurers are still denying prescriptions for these drugs at a higher rate than those for comparable cardiometabolic agents.

Between 2017 and 2019, PCSK9 inhibitors were added to clinical practice guidelines on cholesterol, their initially sky-high price tags were cut by 60%, and their labeling indications were expanded. It was hoped that all of those actions would have a major impact on their availability in real-world practice, say Diane E. MacDougall, MS (Family Heart Foundation, Fernandina Beach, FL), and colleagues in a research letter published this week in Circulation: Cardiovascular Quality and Outcomes.

However, their analysis of prescriptions for various cardiovascular and cardiometabolic drugs found that those for PCSK9 inhibitors were rejected by insurers at a rate of 31%. This compares with rates of between 5% and 15% for other guideline-recommended agents, including sodium-glucose cotransporter 2 (SGLT2) inhibitors.

While the 31% is an improvement over the 46% rejection rate in prior years, MacDougall said the data suggest it’s “still too high for all of those people who are being prescribed PCSK9 inhibitors.”

To TCTMD, she added that despite the high rate of rejection, “we don’t want physicians to give up” on prescribing PCSK9 inhibitors to patients who need them.

We don’t want physicians to give up. Diane E. MacDougall

“This article reinforces what we all see in clinical practice, that when we prescribe a PCSK9, the patients have to either jump through many more hoops or ultimately are rejected and have to find alternatives, which are really nonexistent right now, to get their cholesterol under control,” noted Matthew Budoff, MD (Harbor UCLA Medical Center, Torrance, CA), who commented on the study for TCTMD.

“Not only is it time-consuming for the physician and staff, but it's frustrating because we recommend the therapy and then the insurance companies imply that we're doing something wrong or that we've made the wrong choice,” Budoff noted. “The other problem is that we are held to metrics showing that we get our patients to goals, and one of those goals is LDL cholesterol. If we can't get them to goal because we can't use the tools that are available to us, especially the outcome-proven tools, then we're really in a bad position from both an outcome standpoint for our patients and [in terms of] metrics.”

Discrepancies Tied to Persistence of Initial Policies

For the study, MacDougall and colleagues used the Family Heart Database, which represents more than half of the US census participants, to retrospectively look at prescribing of PCSK9 inhibitors. They compared whether insurers covered the prescription cost or rejected it, as well as whether the prescription was covered but not retrieved by the patient.

The comparator drugs in the analysis were apixaban (Eliquis; Bristol Myers Squibb), sacubitril/valsartan (Entresto; Novartis), dapagliflozin (Farxiga; AstraZeneca), empagliflozin (Jardiance; Boehringer Ingelheim/Eli Lilly), and liraglutide (Saxenda and Victoza; Novo Nordisk). Four of those five agents were among the first 10 drugs that Medicare will be allowed to negotiate prices for beginning in 2026 as part of the first wave of the Inflation Reduction Act (IRA).

When MacDougall et al examined the new prescription status of patients in two time periods, July 2015 to December 2018 (n = 238,704) and January 2019 to December 2021 (n = 470,018), they found that a 2.7-fold increase from the first period to the second in the number of PCSK9 inhibitor prescriptions paid for by insurance. Still, the proportion paid amounted to less than half of what had been prescribed (49.93%).

Meanwhile, 84% of new apixaban prescriptions were paid in the same time period, as were 79% of sacubitril/valsartan, 69% of dapagliflozin, 77% of empagliflozin, and 68% of liraglutide.

In comparison to the nearly one-third of PCSK9 inhibitor prescriptions from 2019-2021 that were rejected by insurers, less than 4% of apixaban prescriptions were rejected during the same time period, with rates of 7% for sacubitril/valsartan, 13% for dapagliflozin, 6% for empagliflozin, and 14.6% for liraglutide.

Looking at prescriptions that were paid for by insurers but not retrieved by the patient also shows significant disparity between PCSK9 inhibitors and comparable agents, which MacDougall and colleagues say could be due to high co-pays that patients can’t afford.

We're undertreating our patients for a decade or more while waiting for these drugs to become more widely available, and that's not acceptable. Matthew Budoff

Budoff said while he and many other physicians expect the situation to slowly get better, it likely reflects a “critical error” on the part of manufacturers when they initially introduced PCSK9 inhibitors at exorbitant prices. “This is still lingering in the minds of clinicians and patients and payers. [Even] though the price point is better, their initial policies of not paying are persisting,” he added.

With the price better aligned with similar drugs, Budoff said there’s nothing more pharmaceutical companies can do, leaving physicians with “one hand tied behind their back” as they try to manage the number one modifiable risk factor for their patients.

“I think it's a slow play by the insurance companies: waiting for these drugs to go generic. But in the meantime, we're undertreating our patients for a decade or more while waiting for these drugs to become more widely available, and that's not acceptable,” he added.