Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors and statins reduce the risk of cardiovascular events proportional to the absolute achieved reduction in low-density lipoprotein cholesterol (LDL-C) and the total duration of therapy, according to an analysis published August 14 in the European Heart Journal.

Brian A. Ference, MD, MSc, FACC, et al., compared the results of the FOURIER and SPIRE trials—which reported that lowering LDL-C with a PCSK9 inhibitor in addition to treatment with a statin reduces the risk of major cardiovascular events—with the results of the Cholesterol Treatment Trialists (CTT) meta-analysis of statin trials. 

The researchers found that PCSK9 inhibitors have “remarkably” similar effects on the risk of cardiovascular events for the same duration of therapy. In the SPIRE-2 trial, one year of treatment with bococizumab reduced the risk of major vascular events by 14.5 percent per mmol/L reduction in LDL-C (hazard ratio [HR], 0.85; 95 percent confidence interval [CI], 0.75-0.98), compared with the 12 percent reduction in major vascular events after one year of treatment with a statin in the CTT meta-analysis.

Similarly, in the FOURIER trial, 2.2 years of treatment with evolocumab reduced the risk of major vascular events by 16 percent per mmol/L reduction in LDL-C (HR, 0.84; 95 percent CI, 0.80-0.88), compared with the 17 percent reduction in major vascular events after two years of treatment with a statin in the CTT meta-analysis. Additionally, the PCSK9 inhibitors and statins also appear to have similar effects on the risk of cardiovascular events during each year of treatment.

According to the authors, the fact that the clinical benefit of both PCSK9 inhibitors and statins depends on the absolute magnitude of the achieved LDL-C reduction and the total duration of treatment has important implications for the ongoing ODYSSEY OUTCOMES trial. Additional analysis of the FOURIER, SPIRE and ODESSEY trials stratified by fasting glucose level should provide more insight into whether there is a clinically relevant effect of PCSK9 inhibitors on the risk of new-onset diabetes.

Keywords: Cholesterol, LDL, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Confidence Intervals, Research Personnel, Fasting, Antibodies, Monoclonal, Cholesterol, Proprotein Convertases, Risk Reduction Behavior, Diabetes Mellitus, Subtilisins, Glucose

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