This article is more than 5 years old. Information may no longer be current.
Evolocumab shows CV benefit in metabolic syndrome
Click Here to Manage Email Alerts
MUNICH — Adults with metabolic syndrome assigned to treatment with the PCSK9 inhibitor evolocumab experienced a greater absolute risk reduction for CV events vs. those without metabolic syndrome assigned to the therapy, with an even greater benefit seen in patients without diabetes, according to a speaker at the European Society of Cardiology Congress.
Metabolic syndrome is a prevalent condition, and it is well known that it predisposes patients to predictively higher risk for both diabetes and CV events, Prakash Deedwania, MD, FACC, professor of medicine at University of California at San Francisco School of Medicine, said during a presentation. Previous studies, he added, have demonstrated that high-intensity atorvastatin therapy was beneficial in reducing CV risk in patients with metabolic syndrome.
“However, residual risk remains,” Deedwania said. “The purpose of this study was to evaluate whether the addition of PCSK9 inhibition, in this case with evolocumab (Repatha, Amgen), in patients with metabolic syndrome, provides further benefit.”
Deedwania and colleagues analyzed data from 27,342 adults with and without metabolic syndrome and established CVD participating in the FOURIER trial, a randomized, doubled-blind, placebo-controlled study. Metabolic syndrome was defined by meeting at least three of the following criteria: HbA1c of at least 6.5% or a fasting blood sugar of at least 11 mg/dL; waist circumference of at least 102 cm for men or 88 cm for women; BP of at least 135 mm Hg systolic/85 mm Hg diastolic; triglyceride level of at least 1.7 mmol/L and HDL of at 40 mg/dL or less for men and 50 mg/dL or less for women. The primary endpoint was CV death, MI, stroke, hospitalization for unstable angina or coronary revascularization. Key secondary outcomes included CV death, MI and stroke. The researchers also assessed adverse events, including new-onset diabetes and glycemic status before vs. after initiation of therapy. Analyses were adjusted for age, race, sex, history of diabetes, MI or congestive HF, smoking status, LDL and high-intensity statin use at baseline.
Within the cohort, 60% of participants had metabolic syndrome at baseline (mean age, 62 years; 28% women; 87% white; mean BMI, 31 kg/m²), making FOURIER one of the largest studies of patients with the condition, Deedwania said. These patients tended to be younger and had a higher BMI vs. those without metabolic syndrome, and high-intensity statin therapy was used more among those with metabolic syndrome, Deedwania said.
Researchers found that patients with metabolic syndrome assigned evolocumab experienced a slightly lower mean reduction in LDL vs. those without metabolic syndrome (58% vs. 61%; P < .00001 for both).
Patients with metabolic syndrome in FOURIER were at substantially higher risk for experiencing a CV event vs. those without the condition, Deedwania said. Compared with participants without metabolic syndrome, those with the condition were at higher risk for experiencing the primary endpoint (15.8% vs. 12.9%) or the key secondary endpoint (10.9% vs. 8.5%), with a between-group separation observed early on in the study, Deedwania said.
However, participants with metabolic syndrome also experienced greater risk reduction for the primary endpoint (HR = 0.83; 95% CI, 0.76-0.91) vs. those without metabolic syndrome (HR = 0.89; 95% CI, 0.79-1.01). Those with metabolic syndrome assigned evolocumab similarly experienced a 24% risk reduction for secondary endpoints (HR = 0.76; 95% CI, 0.68-0.86) vs. a 16% risk reduction for those without metabolic syndrome (HR = 0.86; 95% CI, 0.74-1.01), Deedwania said.
Evolocumab was safe and well tolerated in participants with metabolic syndrome, Deedwania said, with no increased risk for diabetes observed in the subgroup, and no changes in fasting glucose or HbA1c levels during the study.
“It appears that, the higher the absolute risk, the greater the (risk) reduction,” Deedwania said during a discussion following the presentation, adding that the analysis may help distinguish which patients can benefit most from PCSK9 inhibition therapy.
“With expensive drugs like this, you can identify those who are at highest risk, and that is a very important, everyday question we are faced with,” Deedwania said. – by Regina Schaffer
Reference:
Deedwania P, et al. Late-Breaking Pharmacological Science. Presented at: European Society of Cardiology Congress; Aug. 25-29, 2018; Munich.
Disclosure: Deedwania reports he has received consultant fees from Sanofi.