ACC 2026 Adding evolocumab to statins reduces MACE even without overt atherosclerosis
- 01-04-2026
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medwireNews: Adding the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab to background statin therapy substantially reduces the risk for a major adverse cardiovascular event (MACE) even in high-risk patients with diabetes who do not have significant atherosclerosis, shows a trial analysis.
“These data support intensification beyond statins in such patients earlier in the atherosclerotic cardiovascular disease process and targeting LDL-C [low-density lipoprotein cholesterol] goals typically reserved for very high-risk secondary prevention patients,” say Nicholas Marston (Brigham and Women’s Hospital, Boston, Massachusetts, USA) and colleagues in JAMA.
The findings were also presented at the ACC.26 in New Orleans, Louisiana, USA.
The researchers analyzed data from the previously published VESALIUS-CV trial, which included 12,257 high-risk patients with atherosclerosis or diabetes but no prior myocardial infarction (MI) or stroke, and demonstrated that the combination treatment significantly reduced the risk for MACE.
The analysis concentrated on 3655 patients from the diabetes cohort (≥10 years’ duration, daily insulin use, or microvascular disease) who had an LDL-C level of at least 90 mg/dL (2.3 mmol/L) despite at least 2 weeks of stable, optimized, lipid-lowering therapy. None of the cohort had atherosclerosis, defined as a history of arterial revascularization, arterial stenosis of 50% or above, or a coronary artery calcium scan Agatston score of 100 or above.
Among the participants, 1849 received treatment with evolocumab 140 mg every 2 weeks and 1806 received matching placebo. The median age of the patients was 65 years, and 57% were women. The median BMI was 31.4 kg/m2. The median baseline LDL-C level was 132 mg/dL (3.4 mmol/L), and the majority (89%) of patients were receiving lipid-lowering therapy, including 64% receiving high-intensity statins.
At week 48, LDL-C testing in 548 patients revealed that evolocumab treatment was associated with a significantly greater reduction from baseline compared with placebo, with a least squares mean difference of 51%, at a median level of 52 mg/dL (1.3 mmol/L) versus 111 mg/dL (2.9 mmol/L).
The team reports that the co-primary endpoint of 3-point MACE (coronary heart disease death, MI, or ischemic stroke) occurred in 83 of the 1849 patients treated with evolocumab versus 117 of the 1806 patients given placebo, at a 5-year rate on Kaplan-Meier analysis of 5.0% versus 7.1%, and a significant hazard ratio (HR) in favor of PCSK9 inhibitor use of 0.69.
The results for the other co-primary endpoint of 4-point MACE, with the addition of ischemia-driven arterial revascularization, were similar, occurring in a corresponding 127 versus 178 patients, yielding 5-year rates of 7.6% versus 10.5%, and a significant HR of 0.69 in favor of evolocumab.
Further analysis indicated that evolocumab was associated with significantly better 5-year outcomes for each of the individual MACE components. In addition, all-cause mortality as a secondary outcome was reduced significantly more with evolocumab than placebo, at an incidence of 7.4% versus 9.5%, and a HR for death of 0.76.
In an accompanying editorial, Philip Greenland and Donald Lloyd-Jones, both from Northwestern University Feinberg School of Medicine in Chicago, Illinois, USA, write that the VESALIUS-CV trial results expand the “treatment options for a specific group of higher-risk patients,” who have atherosclerotic cardiovascular disease or high-risk diabetes.
However, they underline that several key questions “remain for many lower-risk primary prevention patients not achieving LDL-C goals with statins and other lipid-lowering medications,” regarding who may benefit from “earlier and more intensive lipid-lowering treatment at younger ages.”
While awaiting answers, the editorialists advise that “clinicians should double down on risk assessment and treatment of all known risk factors, as recommended by existing primary prevention guidelines.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2026 Springer Healthcare Ltd, part of Springer Nature
JAMA 2026; doi:10.1001/jama.2026.3277
