Combination of Statins, Ezetimibe Could Prevent Thousands of Heart Attacks

Treating patients hospitalized with myocardial infarction (MI) with a lipid-lowering therapy (LLT) combination of statins and ezetimibe could prevent thousands of further cardiovascular events, according to new research from Lund University and Imperial College London.1

Cardiovascular disease (CVD) is statistically the most common cause of death globally, with MI the most common acute event. If an individual survives MI, the risk for heart failure or heart attacks is significantly higher for the first year, as the blood vessels are more sensitive and therefore more susceptible to blood clots.

High-potency statins have long been the standard treatment for MI survivors during that first year; however, most patients are unable to reach treatment goals solely using this medication.2

“Today’s guidelines recommend stepwise addition of lipid-lowering treatment. But it’s often the case that this escalation takes too long, it’s ineffective and patients are lost to follow-up,” said Margrét Leósdóttir, an associate professor at Lund University and senior cardiology consultant at Skåne University Hospital. “By giving patients a combination treatment earlier, we could help to prevent many more heart attacks.”2

The study included 35,826 LLT-naïve patients (median age, 65.1 years) hospitalized for MI between 2015-2022 and discharged on statin therapy. The risk of major adverse cardiovascular events (MACE), components of MACE, and cardiovascular death was compared between ezetimibe added to statins ≤12 weeks after discharge as reference, from 13 weeks to 16 months, or not at all.1

Among the included patients, 6040 (16.9%) received ezetimibe early, 6495 (18.1%) received it late, and 23,291 (65.0%) received no ezetimibe. Of these patients, 33,499 (93.5%) had available low-density lipoprotein cholesterol (LDL-C) level measurements at baseline and 20,351 (56.8%) at both cardiac rehabilitation follow-up visits (6-10 weeks and 1 year). Although the early combination therapy cohort had the highest baseline LDL-C, over half of that subgroup had achieved the target LDL-C level 1 year after discharge. Although the next 3 years saw goal proportion increase across all 3 groups, the early group still had the most overall.

Leósdóttir and colleagues also indicated that, during a median follow-up of 3.96 years, 2570 patients experienced MACE. Compared with the early combination cohort, the late cohort had a higher risk at 1 and 2 years after MI, which lost statistical significance at 3 years. The non-ezetimibe cohort exhibited a higher risk at 1, 2, and 3 years.

Further analysis showed the adjusted hazard ratio (aHR) of MACE over 3 years was 1.14 (95% CI, 0.95-1.41) for those receiving ezetimibe and 1.29 (95% CI, 1.12-1.55) for those not receiving the combination therapy. Additionally, cardiovascular death exhibited aHRs at 3 years of 1.64 (95% CI, 1.15-2.63) and 1.83 (95% CI, 1.35-2.69) for the late- and no-ezetimibe groups, respectively.

Overall, the early use of combination LLT was associated with a reduction in all-cause death (odds ratio [OR], 0.526: 95% CI, 0.378-0.733). Moving from statin monotherapy to an early combination strategy would necessitate a number needed to treat (NNT) of 53 (95% CI, 32-125) to prevent 1 MACE. Moving from a delayed to an early combination strategy would require an NNT of 143 to prevent 1 MACE. When examined in conjunction with the study population, investigators noted that this approach could have prevented 447 events.

“This study shows that we could save lives and reduce further heart attacks by giving patients a combination of two low-cost drugs. But at the moment, patients across the world aren’t receiving these drugs together," said Professor Kausik Ray, MD, a professor of public health and honorary cardiologist at Imperial College London. "That’s causing unnecessary and avoidable heart attacks and deaths – and also places unnecessary costs on healthcare systems. Our study shows the way forward; care pathways must now change for patients after this type of heart event.”3

References

1. Leosdottir M, Schubert J, Brandts J, et al. Early ezetimibe initiation after myocardial infarction protects against later cardiovascular outcomes in the SWEDEHEART registry. Journal of the American College of Cardiology. 2025;85(15):1550-1564. doi:10.1016/j.jacc.2025.02.007

2. Lund University. Simple medication can save the lives of cardiac patients. Eurekalert! April 14, 2025. Accessed April 14, 2025. https://www.eurekalert.org/news-releases/1080280
3. Imperialspark. Combination of drugs could prevent thousands of heart attacks. EurekAlert! April 14, 2025. Accessed April 15, 2025. https://www.eurekalert.org/news-releases/1080313.