Evolocumab Reduces Cardiovascular Risk in Metabolic Syndrome Patients

Prakash Deedwania, MD

A new study’s findings showed that evolocumab (Repatha) significantly reduced low-density lipoprotein cholesterol (LDL-C) and the risk of cardiovascular (CV) events in patients with metabolic syndrome, a collection of risk factors that increase chance of developing diabetes and major adverse CV events.

Additionally, the PCSK9 inhibitor did not increase risk of safety events, new-onset diabetes, or worsening glycemic control.

Although previous studies have shown that intensive lipid-lowering therapy with high dose statins significantly reduced major adverse cardiovascular events (MACE) in both metabolic syndrome and atherosclerotic CV disease (ASCVD) patients, investigators noted that the role of the PCKSK9 inhibitors in reducing MACE has not been established in those with metabolic syndrome.

The results of the study revealed that evolocumab similarly reduced CV risk in patients with and without metabolic syndrome. Due to their heightened baseline risk, those with the syndrome without diabetes had a greater absolute risk reduction (ARR) with evolocumab treatment.

Prakash Deedwania, MD, and colleagues used the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial to evaluate the safety and efficacy of evolucumab therapy in patients with metabolic syndrome.

The randomized, double-blind trial had enrolled 27,342 patients with ASCVD. Of them, 16,361 patients (59.8%) met most or all criteria for metabolic syndrome. Participants were randomized 1:1 to receive evolocumab subcutaneously (either 140 mg every 2 weeks or 420 monthly), or a placebo injection.

The primary endpoint of the FOURIER population assessment was the composite of CV death, myocardial infarction (MI), stroke, coronary revascularization, or hospitalization. The secondary endpoint was the composite of CV death, MI stroke. All efficacy analyses of treatment drug versus placebo was conducted on an intention-to-treat basis.

Deedwania and colleagues found that evolocumab reduced the primary endpoint compared with placebo in metabolic syndrome patients (13.5% with evolocumab vs 15.8% with placebo; HR, .83; 95% CI, 0.76-0.91). A similar degree was observed in patients without metabolic syndrome (11.2% vs 12.9%; HR, .89; 95% CI, 0.79–1.01, P = .39).

The secondary endpoint was similarly reduced in patients with metabolic syndrome (8.6% vs 10.9%; HR, .76; 95% CI, 0.68-0.86), and without (6.8% vs 8.5%; HR, .86; 95% CI, 0.74-1.01, P = .23).

For the primary endpoint, the hazard ratio for patients with diabetes and metabolic syndrome was 0.85; for diabetes without metabolic syndrome, 0.78; metabolic syndrome without diabetes, 0.80; and neither diabetes nor metabolic syndrome, 0.91.

The absolute risk reduction with evolocumab over the three-year treatment period was 2.1% in metabolic syndrome patients with diabetes; 4.9% in non-syndrome patients with diabetes; 2.5% in patients with metabolic syndrome and no diabetes; and 0.9% in patients with neither.

The investigators suggested that patients with ASCVD and diabetes, and metabolic syndrome patients without diabetes benefitted more from evolocumab therapy. The data highlights the need for clinicians to identify high-risk patients who are more likely to experience greater CV risk reduction in response to PCSK9 inhibition.

“The message is to identify your patients who have metabolic syndrome—and they may be the patients who benefit [from PSCK9 inhibition therapy] the most,” Deedwania urged clinicians in an interview with HCPLive®.

Addressing the limitations of the expensive therapy, he continued, “If you have to choose your best strategy to get the best bigger bang for the buck, I would say people with metabolic syndrome will have that because they get bigger benefits. Those without metabolic syndrome will also benefit, but not nearly as much.”

The study, “Efficacy and Safety of PCSK9 Inhibition With Evolocumab in Reducing Cardiovascular Events in Patients With Metabolic Syndrome Receiving Statin Therapy,” was published online in JAMA Cardiology.