Is cardiology ready for the PCSK9 inhibitor era? Some don’t think so

The case for PCSK9 inhibitors is strong following the American College of Cardiology’s 67th annual symposium in Orlando, but some physicians remain wary of the medication, citing gaps in clinical evidence and questioning if cardiology is ready for the widespread distribution of such pricey drugs.

Since PCSK9 inhibitors were introduced to the American market in 2015, study after study—most notably FOURIER in 2016 and this year’s ODYSSEY trial—has proven the efficacy of medications like evolocumab in lowering “bad” lipid levels in heart patients whose statin regimens alone aren’t getting the job done. The inhibitors have been shown to reduce coronary atheroma volume, improve atheroslerotic cardiovascular disease (ASCVD) in very high-risk patients and lower LDL-cholesterol in those with familial hypercholesterolemia (FH). But access remains limited thanks to out-of-pockets costs that can top $14,000 and strict approval guidelines means access.

Salim S. Virani, MD, PhD, said at ACC 2018 there’s a lot cardiologists can learn from the clinical trials to date, including the fact that PCSK9 inhibitors have an excellent safety and tolerability record, they’re effective reducers of ASCVD and harmful fat levels and they can reduce the frequency of need for LDL apheresis in FH patients—but there’s also a lot clinicians don’t know.

“Are we ready?” Virani asked. “Are we doing what we need to do to prescribe PCSK9 inhibitors the way they were prescribed in trials?”

Maybe, he said, if cardiologists can recognize the barriers they still face. While nearly 40 percent of patients were prescribed PCSK9 inhibitors for primary prevention in a 2017 trial, Virani said the majority—60.4 percent—leaned on the drugs as a form of secondary prevention. But there’s a lack of evidence for the efficacy of PCSK9 inhibitors in primary prevention, and more research needs to be done before clinicians can determine the long-term efficacy, long-term safety, LDL-cholesterol thresholds and costs associated with the medication.

It’s also important to maximize statin intensity and statin adherence in patients before turning to PCSK9 inhibitors, Virani said, especially since PCSK9 inhibitors and statins reportedly have therapeutically equivalent effects on the risk of cardiovascular events per unit change in LDL-cholesterol. The inhibitors could also influence new onset diabetes, he said, though more research is needed before clinicians can draw any conclusions.

Pamela Bowe Morris, MD, said at the same session there’s an abundance of information available to cardiologists when it comes to cholesterol management in complicated patients, but the most important thing is making a strong decision and sticking with that treatment plan.

“When it comes to clinical guidelines for managing lipids in complex patients, we have a myriad of guidelines available to us,” she said. “I really don’t care what guideline you follow. Just pick one and implement it. You would be saving lives left and right.”