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A prespecified analysis of FOURIER is detailing the impact of evolocumab on CV events and LDL-C in patients with metabolic syndrome.
Information from a prespecified analysis of the FOURIER trial is shedding light on the safety and efficacy of evolocumab (Repatha) for reducing cardiovascular events in patients with metabolic syndrome already receiving statin therapy.
Data from the analysis indicate use of the PCSK9 inhibitor in this patient group resulted in significant reductions in low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk in patients without increasing new-onset diabetes, worsening glycemic control, or causing any major safety events.
“These data suggest that treatment with evolocumab in patients with ASCVD and diabetes or MetS is efficacious and safe. These results can be helpful in guiding the selection of patients who are most likely to benefit from treatment with PCSK9 inhibitor therapy,” wrote study investigators.
With patients with metabolic syndrome at an increased cardiovascular risk and previous studies demonstrating benefit in patients with atherosclerotic cardiovascular disease (ASCVD), FOURIER investigators designed the current study as a prespecified analysis to investigate the effect of evolocumab in patients with and without metabolic syndrome.
Briefly, FOURIER enrolled patients 40-85 years of age with ASCVD and additional cardiovascular risk factors between February 2013-June 2015. Patients in the study were randomized in a 1:1 ratio to subcutaneous evolocumab or matching placebo injection. In total, 27,342 patients from the original trial were included in the secondary analysis. Of the 27,342 patients included in the analysis, 16,361 were considered as having metabolic syndrome.
To be defined as having metabolic syndrome, patients need to meet 3 of 5 prespecified criteria. These criteria included a waist circumference more than 102 cm for men or more than 88 cm for women, triglyceride levels of 150mg/dL or higher, HDL-C less than 40 mg/dL for men or less than 50 mg/dL for women, blood pressure of 130mm Hg or higher/85mm Hg or higher, and a fasting glucose level of 110 mg/dL or higher.
The primary end point for the analysis was cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. Investigators also included a key secondary end point, which was cardiovascular death, myocardial infarction, or stroke.
Upon analysis, patients with metabolic syndrome were at a higher risk of cardiovascular events than those without metabolic syndrome for both the primary (aHR, 1.31; 95% CI, 1.18-1.46; P <.001) and secondary end point (aHR, 1.38; 95% CI, 1.20-1.57; P <.001). Results of the analysis also indicated evolocumab was associated with similar reductions in LDL-C in patients with metabolic syndrome and those without metabolic syndrome (median, 92; 79-109 mg/dL vs 30; 19-48 mg/dL; P <.001).
Further analysis revealed the hazard ratios for the primary end point with evolocumab vs placebo were 0.83 (95% CI, 0.76-0.91) and 0.89 (95% CI, 0.79-1.01) in patients with and without metabolic syndrome, respectively (P for interaction=.39). When assessing for the key secondary end point, the hazard ratios were 0.76 (95% CI, 0.68-0.86) and 0.86 (95% CI, 0.74-1.01) for those with and without metabolic syndrome, respectively (P for interaction=.23).
Investigators also pointed out evolocumab was not associated with an increase in risk for new-onset diabetes or other major safety outcomes, such as worsening glycemic control.
Investigators noted limitations within their analysis. These limitations included being an analysis of a trial that applied strict entry criteria, the original trial not being powered for subgroup analyses, and reliance on clinical data and not independent review to determine metabolic syndrome.
This study, “Efficacy and Safety of PCSK9 Inhibition With Evolocumab in Reducing Cardiovascular Events in Patients With Metabolic Syndrome Receiving Statin Therapy,” was published in JAMA Cardiology.