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Early combination lipid-lowering therapy with high-intensity statins and ezetimibe protects against later cardiovascular events, according to research.

Early combination lipid-lowering therapy (LLT) with high-intensity statins and ezetimibe should be the standard of care for patients with myocardial infarction (MI), according to a study published in the Journal of the American College of Cardiology.

“The need for combination therapy is inevitable for most patients after an MI. A delayed approach to LLT escalation is associated with avoidable harms,” wrote corresponding author Margret Leosdottir, MD, PhD, of Skåne University Hospital, Malmö, Sweden, and study coauthors. This led her team to investigate whether promptly adding ezetimibe to a high‑intensity statin confers measurable clinical advantages over a stepped‑up strategy or monotherapy.

Study Design & Cohort Characteristics

For the observational study, the researchers mined Sweden’s nationwide SWEDEHEART registry for LLT‑naïve adults discharged after an MI between 2015 and 2022 (n=35,826). All patients received statins at hospital discharge; ezetimibe initiation defined treatment groups:

• Early combination—add‑on within 12 weeks of discharge (16.9 %).
• Late combination—add‑on at 13 weeks to 16 months of discharge (18.1 %).
• Statin monotherapy—no ezetimibe (65.0 %).

High‑intensity statins were used by 98 % or more of every cohort.

Clinical Outcomes Over Four Years

During a median follow‑up of 3.96 years, 2,570 patients experienced major adverse cardiovascular events (MACE) and 440 died from cardiovascular causes, according to findings. Unadjusted MACE incidence per 100 patient‑years was 1.79 with early combination therapy, 2.58 with late combination therapy, and 4.03 with statin alone. Relative to early initiation, weighted risk differences for late initiation were 0.6 % at one year, 1.1 % at two years, and 0.7 % at three years, yielding a three‑year hazard ratio (HR) of 1.14. Statin monotherapy fared worse: risk differences of 0.7 %, 1.6 %, and 1.9 % across the same intervals and an HR of 1.29, the researchers reported.

Risk differences in cardiovascular death at 3 years were similar, the study found. Compared with early ezetimibe add‑on, HRs for cardiovascular death were 1.64 with late combination therapy and 1.83 with no ezetimibe.

“Approximately two‑thirds of patients had not received add‑on therapy with ezetimibe by 16 months after MI,” the authors observed, “and those patients experienced the highest risk of MACE and cardiovascular death.”

Implications for Clinical Practice

These real‑world data argue strongly for routine, immediate initiation of high‑intensity statins plus ezetimibe after MI.

“Care pathways can be streamlined with tangible health benefits if the standard of care for LLT after an MI consists of an early combination of high-intensity statins with ezetimibe,” the authors concluded.