Adding ezetimibe to statin treatment early after a heart attack could prevent many subsequent cardiac events and save lives, according to a major study that could lead to changes in clinical guidelines.
The findings, published in the Journal of the American Heart Association, indicate that lowering low-density lipoprotein (LDL) cholesterol levels as quickly as possible using multiple drugs after a heart attack offers greater benefits than a more graduated method.
In countries with around 100,000 hospital admissions each year for myocardial infarction (MI), such as the U.K., it could prevent approximately 5,000 MIs over a 10-year period.
Global guidelines currently recommend stepwise titration of lipid-lowering therapy (LLT), but escalation often takes too long or is ineffective and patients are lost to follow-up, according to lead author Margrét Leósdóttir, PhD, an associate professor at Lund University in Sweden.
“The best-case scenario would be to treat only those who we know will respond to therapy, to avoid over-medication and unwanted side effects, and to decrease healthcare-related costs. This is what precision medicine will bring us in the future,” she told Inside Precision Medicine.
“But for now, when we do not know which patients will benefit from treatment, delaying the use of combination lipid-lowering therapy or using high-intensity statin monotherapy alone as standard of care in the MI patient population, is associated with avoidable harm.”
The team examined whether delaying the addition of ezetimibe to statins after an MI was associated with worse cardiovascular outcomes compared with an approach using the combination early on.
In an intriguing approach, the team used advanced statistical models to replicate a clinical trial using registry data from 35,826 Swedish patients who had experienced recent MI between 2015 and 2022.
Of these individuals, 16.9% received ezetimibe early on, within 12 weeks of discharge after MI, 18.1% received ezetimibe late, between 13 weeks and 16 months after discharge, and 65.0% had not received ezetimibe by 16 months after discharge. High-intensity statins were used in at least 98% of the three groups.
Use of ezetimibe combination therapy, early or late, resulted in a greater proportion of patients achieving an LDL-C of less than 1.4 mmol/l (
Over a median of 3.96 years, 2,570 patients had a major adverse cardiovascular event (MACE) consisting of death, MI, or stroke. This included 440 cardiovascular deaths.
MACE at one year was 1.79 per 100 patient-years with early ezetimibe, versus 2.58 with late treatment, and 4.03 with no such treatment.
Early combination therapy in which ezetimibe was added to background high-intensity statin therapy was associated with greater absolute and relative benefits in terms of MACE compared with a delayed combination therapy strategy.
The authors noted that the approximately two-thirds of patients who had not received add-on ezetimibe by 16 months post MI experienced the highest risk of MACE and cardiovascular death.
“The need for combination therapy is inevitable for most patients after an MI,” the team concluded. “A delayed approach to LLT escalation is associated with avoidable harms.”
