From the start, the debate about the cholesterol-lowering therapies proprotein convertase subtilisin/kexin type 9 (PCKS9) inhibitors hasn’t been about whether they work—they do—but whether they change clinical outcomes in ways that justify their $14,000 annual cost.
So far, there are 2 approved PCSK9 inhibitors—evolocumab and alirocumab—which have been shown to reduce low-density lipoprotein (LDL) cholesterol up to 60% in clinical trials. The trouble is, payers have made it clear that only the highest-risk patients will gain access to the drugs; in general, patients must try to lower LDL cholesterol with statins before using the more powerful injected drugs.
On the heels of studies
that show how hard it can be to get a prescription filled for PCSK9 inhibitors, researchers at the American Heart Association Scientific Sessions in Anaheim, California, on Monday presented follow-up data from the FOURIER trial. In March, initial results from FOURIER showed that the PCSK9 inhibitor evolocumab, sold as Repatha, reduced cardiovascular events, especially after the first year.
Monday’s presentations looked at some of the highest-risk patients—those with peripheral artery disease (PAD) and those with a history of myocardial infarction (MI) and residual coronary artery disease (CAD). The abstracts concluded that focusing on certain risk factors could allow physicians to target treatment to patients most in need; the results with data from patients with at least 2 heart attacks or residual CAD concluded, “These data may permit clinicians to target PCSK9 inhibition to patients who benefit the most.”
Peripheral artery disease.
This subanalysis was designed to evaluate whether patients with PAD taking standard background therapy, including statins, were at higher ischemic risk—and if lowering their LDL cholesterol with evolocumab could reduce the number of CV events.1
Patients with PAD are also at risk for amputations.
Of the more than 27,000 patients enrolled in FOURIER, 3642 had PAD. They were older, and had higher rates of hypertension, diabetes, and smoking than the overall study population. At 30 months, the patients with PAD taking placebo had a 60% higher rate of the primary end point (a composite of CV death, heart attack, stroke, hospitalization for unstable angina, and revascularization; 16.8% vs 12.1%), and the PAD patients on placebo had an 80% higher rate of CV death, stroke, or heart attack (13% vs 7.6%). Notably, evolocumab reduced LDL cholesterol in these patients from an average of 93 mg/dL to 31 mg/dL. Patients taking evolocumab had no significant increase in adverse events relative to those taking placebo.
The researchers concluded that patients with PAD taking statins remained at “heightened ischemic risk,” but that “profound further lowering of LDL cholesterol with evolocumab significantly and safety reduces this ischemic risk.”
History of heart attacks.
Within FOURIER, a total of 8402 patients had experienced a heart attack within 2 years, and 5285 (24%) had at least 2 heart attacks; also, 5618 patients (25%) had residual, multivessel CAD. Thus, these groups were at especially high risk for future CV events. Results showed that treating these high-risk subgroups with evolocumab lowered LDL cholesterol and caused both relative and absolute risk reductions compared with the placebo group; the 3% absolute risk reduction over 3 years translated into a number-needed-to-treat of 33 to avoid a CV event.
“Patients with more serious manifestations of CAD, including those with a more recent MI, with multiple prior MIs or with residual multivessel CAD are at high risk for major vascular events and experienced substantial risk reductions with evolocumab,” the authors concluded.
Whether this translates into easier times with payers for the highest-risk patients remains to be seen. When the initial FOURIER results were presented in March, cardiologists were impressed, but payers were less moved. Amgen, the maker of evolocumab, anticipated this and offered refunds if a patient had a heart attack while taking the drug. Eliot A. Brinton, MD, of the Utah Lipid Center, told The American Journal of Managed Care®
in October that in his experience access is still difficult.
“We do have convincing trial data now with the FOURIER study with evolocumab; we should have similar data soon with the other drug, which is alirocumab (sold as Praluent by Sanofi/Regeneron). I’m hopeful that this will become less of an issue. But it remains a very important fact that just simply writing a prescription for a PCSK9 inhibitor does not give one immediate access to the drug.”
- Bonaca MP, Nault P, Giugliano RP, et al. Evolocumab and outcomes in patients with peripheral artery disease. Presented at the American Heart Association Scientific Sessions, Anaheim California; November 11-15, 2017. LBS-2.
- Sabatine MS, deFerrari GM, Giugliano RP, et al. Clinical benefit of evolocumab in patients with a history of MI: an analysis from FOURIER. Presented at the American Heart Association Scientific Sessions, Anaheim California; November 11-15, 2017. LBS-2.