- A new study found that adding a second drug early after a heart attack may save lives.
- Those who added ezetimibe to a statin had fewer complications and deaths.
- The authors say that early combination therapy should become the standard of care.
- Experts say addressing underlying inflammation can also help control cholesterol.
New research from Sweden suggests that starting a second cholesterol-lowering drug soon after a heart attack may help save lives.
According to the study, published in the April 2025 issue of the Journal of the American College of Cardiology, people who received ezetimibe (brand name Zetia) with their statin therapy within 12 weeks of a heart attack had fewer heart-related complications and deaths than those who waited longer or never added ezetimibe at all.
The National Library of Medicine explains that ezetimibe helps reduce the amount of low-density lipoprotein (LDL) cholesterol in your blood by preventing cholesterol from being absorbed in the small intestine.
LDL cholesterol is the so-called “bad” cholesterol associated with clogged arteries and an increased risk of cardiovascular diseases such as heart attack and stroke.
Ezetimibe is sometimes prescribed for people who can’t tolerate statins. It may also be used as an add-on treatment when statins do not sufficiently lower cholesterol.
This medication works differently from statins, which exert their cholesterol-lowering effects by slowing down the liver’s production of the waxy substance.
Early combination therapy after heart attack may save lives
To arrive at their conclusion, the researchers analyzed data from more than 35,000 patients hospitalized for heart attacks (myocardial infarction) between 2015 and 2022, using the comprehensive SWEDEHEART registry in Sweden.
Most patients were prescribed high-intensity statins at discharge, but a subset also began taking a second medication, ezetimibe, within the first 12 weeks after discharge.
The study categorized patients into three groups: those who started ezetimibe early (within 12 weeks), those who started late (13 weeks to 16 months after discharge), and those who never received ezetimibe during this period.
Importantly, the analysis used advanced statistical methods — specifically, a clone-censor-weight framework — to emulate a randomized clinical trial and minimize biases
Results showed that patients who started ezetimibe early in combination with statins had a significantly lower risk of major adverse cardiovascular events (MACE), which include death, another heart attack, or stroke, compared to those who delayed ezetimibe or never took it.
One-year incidence rates of MACE were 1.79 per 100 patient-years in the early ezetimibe group, compared with 2.58 in the late group and 4.03 in those without ezetimibe.
At three years, the hazard ratio for MACE was 1.14 for late versus early treatment (not statistically significant) but was 1.29 for no ezetimibe versus early treatment, indicating substantially higher risk without ezetimibe.
Cardiovascular death was also significantly higher in the late and no ezetimibe groups compared to early treatment.
Additionally, early combination therapy led to a greater proportion of patients achieving guideline-recommended LDL cholesterol targets (<1.4 mmol/L or <55 mg/dL) within one year.
What are the implications for heart attack patients?
The study underscores that a stepwise approach — starting with statins and adding ezetimibe only if LDL cholesterol goals are not met — inevitably delays optimal cholesterol lowering and is associated with avoidable harm.
As the authors note, approximately 75–80% of post-heart attack patients fail to reach LDL goals with statin therapy alone; initiating combination therapy early can improve outcomes and reduce future cardiovascular events.
To maximize protection, the researchers advocate that care pathways for heart attack patients should be updated to implement early combination therapy with statins and ezetimibe as standard care, potentially even before hospital discharge.
Arun Manmadhan, MD, assistant professor of cardiology at Columbia University Irving Medical Center, who was not involved with the study, said the findings align with a broader body of research showing that sustained, low LDL cholesterol levels are associated with fewer heart attacks and strokes.
“This is even more important in people who have already experienced one of these events,” he said, “because lowering the cholesterol levels, in addition to optimizing other cardiac risk factors, is one of the most effective and proven ways to prevent a second event.”
Manmadhan said that, in his opinion, this study adds to the evidence that patients who have had a heart attack or stroke should have their cholesterol levels aggressively managed, both through lifestyle and medications.
“This study suggests that time is also an important factor,” he added. “[The] earlier and faster cholesterol levels are aggressively controlled to recommended levels after a heart attack, the better it is for preventing future cardiovascular events.”
What can patients do beyond cholesterol-lowering drugs?
Markyia Nichols, MD, MPH, RDN, a CDC-certified lifestyle coach and chief medical officer at Ciba Health, said patients should know that “cholesterol isn’t the enemy.”
“It’s a response,” she explained. “Cholesterol is essential for life. It builds hormones, stabilizes cells, and repairs tissue. If cholesterol is rising, it’s critical to ask what the body is trying to repair or protect against.”
According to Nichols, inflammation is the real problem, not cholesterol. A diet high in sugar, processed seed oils, and ultra-processed foods, insulin resistance, metabolic dysfunction, chronic stress, and exposure to toxins can all factor into creating inflammation.
“Once the heart lining is damaged, the body sends cholesterol as a patch,” she said. “Cholesterol doesn’t cause the ‘fire.’ It acts more like the ‘firefighters.’”
Nichols added that, digging deeper, LDL only becomes dangerous when it’s oxidized due to poor nutrition.
Circling back to the study, she told Healthline that while adding ezetimibe to statins post-early heart attack may lower cholesterol, it’s not addressing the root causes of the problem. Patients also need to focus on nutrition.
“Ask for labwork that tests levels of magnesium, omega-3s, vitamin D, and vitamin K2,” she advised. “You can’t rebuild a healthy heart without healthy raw materials.”
She also suggests looking to see whether your markers of inflammation, such as C-reactive protein, homocysteine, and insulin, are high.
Further, look for any sources of inflammation you might have, like a poor diet, stress, toxins, or an unhealthy gut.
Nichols concluded by saying that you may need to see a board-certified doctor trained in root-cause medicine to determine what’s causing your inflammation.
However, addressing this can help you heal the underlying causes of your high cholesterol.
