A review of 24 trials covering more than 10,000 patients confirmed earlier findings that PCSK9 inhibitors dramatically reduce cholesterol and risk of heart attacks. But an editorial that appeared alongside the meta-analysis in Annals of Internal Medicine said long-term studies are needed on this new drug class.
The much anticipated arrival of the PCSK9 inhibitors, expected to hit the US market this summer, received another boost with today’s publication of a meta-analysis in the Annals of Internal Medicine.1 The review covering studies of more than 10,000 patients confirmed that the new drug class dramatically reduces low-density lipoprotein (LDL) cholesterol and reduces the risk of heart attacks, leading to reduced mortality.
Researchers evaluated results from 24 trials, and found that treated with PCSK9 inhibitors led to a large reductions in LDL cholesterol levels, with a mean difference of -47.49%. Reduced all-cause mortality ratio (OR) was 0.45; reduced cardiovascular (CVD) mortality OR was 0.50, and reduced myocardial infarction OR was 0.50.1
Eliano Pio Navarese, lead author of the study, told MedPage Today, “The very dramatic findings from our large-scale analysis should open the door for new era in cholesterol treatment. Our findings were robust, and I am confident that the ongoing (PCSK9 drug) trials will confirm them."
But the writers of an accompanying editorial were not ready to fill up their prescription pads, calling for “cautious enthusiasm.” They were most impressed with the reductions in all-cause mortality, heart attacks, and CVD mortality rates. But they noted that these new drugs were tested in trials of small or moderate size, and that most trials had short follow-up periods.2
“Confirmation of these findings in long-term, ongoing, pivotal trials with prespecified primary CVD end points and monitoring of a broad range of adverse events will help establish the role of these novel agents in CVD risk management,” the editorial states.2
Sanofi-Regeneron and Amgen have competing versions of PCSK9 inhibitors before the FDA, and the agency must soon act on the applications, for alirocumab in July and evolocumab in August, respectively. Analysts have called the arrival of these cholesterol-busters the most anticipated pharmacy event of 2015, while formulary managers have said they will not be caught flat-footed in their quest to control the new drugs’ costs.
Pharmacy experts who spoke with The American Journal of Managed Care earlier this year cautioned that the arrival of the PCSK9 inhibitors could mark a new milestone in specialty pharmacy, one in which an expensive, new therapy replaces a generic standby, in this case statins. At the March meeting of the American College of Cardiology, Marc Sabatine, MD, MPH, of Brigham and Women’s Hospital, Boston, insisted that statins were the “foundation” of cholesterol control, but he also said no floor had been established at which reducing cholesterol did not provide some benefit.
1. Navarese EP, Kolodziejczak M, Schulze V, et al. Effects of proprotein convertase subtilisin/kexin type 9 antibodies in adults with hypercholesterolemia: a systematic review and meta-analysis [published online April 28, 2015]. Ann Intern Med. doi:10.7325/M14-2957.
2. Cainzos-Achirica M, Martin SS, Cornell JE, et al. PCKS9 inhibitors: a new era in lipid-lowering treatment? [published online April 28, 2015] Ann Intern Med. doi:73226/M15-0920.