ODYSSEY results a win for PCSK9 inhibitors, but clinicians still wary of barriers

Treatment with the PCSK9 inhibitor alirocumab has been proven successful in reducing both cardiovascular events and all-cause mortality in heart patients, according to ODYSSEY results presented at ACC 18 in Orlando, but the debate surrounding the cholesterol-busting drug is far from over.

ODYSSEY, which focused on the efficacy of alirocumab in decreasing rates of adverse cardiac events and death, has been an anticipated trial since its inception six years ago. But during those six years, PCSK9 inhibitors have been criticized for their high price point—evolocumab, which was popularized by the FOURIER trial, adds up to more than $14,000 a year—and barriers placed on the drugs by insurance companies.

Alirocumab and evolocumab serve similar purposes, ODYSSEY author Gabriel Steg, MD, said. The drugs block the protein PCSK9, which is a validated target for risk reduction in stable atherosclerotic cardiovascular disease (ACD), in patients whose statins or other lipid-lowering therapies aren’t cutting it. Though both medications have been safe and well-tolerated in study populations to date, clinicians claim the process to approve either drug for use in a clinical setting is arduous.

“What I can tell you is, it’s a struggle,” Valentin Fuster, MD, PhD, who wasn’t involved in the study, said. “It’s a struggle. This trial has impact because of the thousands and thousands of people it would apply to. I think something has to be done.”

Steg’s team randomized nearly 20,000 patients with a recent ACS diagnosis to either treatment with alirocumab or a placebo, with a primary endpoint of coronary heart disease death, non-fatal myocardial infarction, stroke or unstable angina. All participants were taking high-intensity statins at high doses, but had continued to record inadequate lipid levels and lacked control over their LDL cholesterol.

The authors found that when compared with placebo treatments, taking 75 mg to 150 mg of alirocumab reduced patients’ instances of ischemic stroke, myocardial infarction and other major adverse cardiovascular events, as well as all-cause death. The drug was proven safe and easy to tolerate for the duration of the trial.

To date, national guidelines don’t recommend treatment with any PCSK9 inhibitors, Steg said; in the study’s population, nearly all patients were prescribed aspirin, and the vast majority were also recommended for beta-blockers, P2Y12 antagonists and angiotensin II receptor blockers. PCSK9 drugs aren’t included in any guidelines, likely for their price tag and other hurdles to access.

Fuster said that not only is paperwork “huge” when it comes to recommending these medications for patients, but clinicians are also faced with a host of questions designed to make the patient an ineligible candidate for the drug.

“It’s very, very hard,” Fuster said. “You go back and forth, and back and forth. And, in the end, you give up, because it’s just not working.”

Because of the difficult nature of attaining drugs like alirocumab and evolocumab, Steg said cardiologists are often faced with the moral dilemma of picking and choosing patients to receive the medication.

“As clinicians, given the cost-conscious environment we’re in, we have to decide, who should we give them to?” he said. “As a clinician, as a cardiologist, I have to start somewhere.”

Still, Fuster said, the ODYSSEY results “were not trivial” and hold the promise of changing standards. He called the study a catalyst in the fight to make PCSK9 inhibitors more widely available to patients who could benefit from them.

“This study will change practice,” he said.

Using an interactive ACC phone app, Steg asked his audience Saturday how many of them, after learning the ODYSSEY results, would change their practices of prescribing PCSK9 inhibitors. Sixty-two percent said yes.

He said he didn’t know if the trial will change access barriers, but the positive evidence surrounding alirocumab is hard to ignore.

“I assume this will sway both patients and physicians and payers and regulators to give better access to these drugs,” he said.