Statin therapy remains a cornerstone for primary and secondary prevention of major adverse cardiac events (MACEs), but prescribing based on patient phenotype identified through imaging may boost its effectiveness, according to a new study.

“While population-level primary-prevention trials have established the efficacy of statins, it remains unclear whether their benefit depends on the extent of underlying atherosclerotic disease. Our work addresses this evidence gap by assessing whether the treatment effect varies with disease characteristics,” lead investigator Bálint Szilveszter, MD, PhD, a researcher at the Semmelweis University Heart and Vascular Centre in Budapest, Hungary, wrote in an email to Medscape Medical News.

“Clarifying this relationship could enable more personalized and also intensified therapy,” Szilveszter added.

Each 10% increase in statin use was associated with a decreased risk for MACE, for example, among those with obstructive coronary artery disease (CAD), high-risk plaque, a calcium score of ≥ 400, or a segment involvement score > 4. In contrast, there was no link between patients with “any CAD” and lower risk for MACE.

By contrast, “in asymptomatic individuals, routine CT screening is not recommended,” Szilveszter said.

The study was published online on August 5, 2025, in JACC: Cardiovascular Imaging.

More Than 8 Years Follow-Up

Szilveszter and colleagues studied 11,026 consecutive adults with stable chest pain referred for clinically indicated coronary CT angiography to assess CAD between January 1, 2013, and December 31, 2020. The population had a mean age of 59 years and 55% were men.

The MACE composite endpoint included all-cause mortality, acute myocardial infarction, or revascularization for unstable angina.

Statin use was based on prescription fills in Hungary’s National Health Service database. Sixty-six percent of patients were treated with a statin during the study period. Median follow-up was 8.3 years from the date of first statin use to an event or end of the study.

Key Findings

MACE was detected in 4.4% of patients, myocardial infarction alone in 0.9%, and all-cause mortality in 3.1%. Following coronary CT angiography, 14% of total patients stopped using statins, 11% started statin therapy, and 40% continued their statin regimen. The remaining patients were not treated with statins.

With each 10% increase in statin use, the risk for MACE was lowered in the presence of:

• Obstructive CAD (adjusted hazard ratio [aHR], 0.91; 95% CI, 0.85-0.97; P = .006)
• High-risk plaque (aHR, 0.82; 95% CI, 0.68-0.98; P = .026)
• Calcium score of ≥ 400 (aHR, 0.93; 95% CI, 0.87-0.99; P = .024)
• Segment involvement score of ≥ 4 (aHR, 0.89; 95% CI, 0.84-0.95; P < .001)

In contrast, results revealed no significant MACE reduction for “any CAD” (aHR, 0.95; 95% CI: 0.85-1.07; P = .411).

“Our message is not to restrict therapy but to better target and support statin use when anatomic disease is demonstrated,” Szilveszter said.

Whether coronary CT angiography can guide therapy in asymptomatic individuals remains under investigation, he added.

“Given radiation and contrast exposure and costs, we need to define the true cost–benefit and select subgroups in whom use may be justified in the future,” he said.

The Protective Role of Fitness

“Statins are widely prescribed. While it is clear that statin users improved some aspects of their lipid profile, the effects of health outcomes are not so obvious and there are some gaps in the knowledge,” Claudio Gil Araújo, MD, PhD, dean of Research and Education at CLINIMEX — Clínica de Medicina do Exercício in Rio de Janeiro, Brazil, wrote in an email to Medscape Medical News.

There has never been a randomized controlled trial comparing statins, exercise, a combination of both, and controls, according to Abraço.

“And unfortunately, due to other interests, it will never happen. However, observational data suggest that those who are fitter will have modest or no benefit in reducing MACE from taking statins,” he said, citing a 2013 study in The Lancet by Peter Kokkinos, PhD, and colleagues that supports that finding.

“It’s better to be highly fit or at least fit than not being fit and taking a statin,” Kokkinos, lead author and director of the Center for Exercise and Aging and professor at Rutgers-New Brunswick School of Arts and Sciences in New Brunswick, New Jersey, said in an interview.

Kokkinos and colleagues classified 10,043 veterans with dyslipidemia into four strata of fitness. They found significant protective effects against MACE with greater fitness levels, and statins conferred the most benefit among those who were least fit. Median follow-up was 10 years, during which 2318 patients died. The risk for death was 18.5% among those taking statins vs 27.7% among those not taking statins (P < .0001).

Therefore, even though the research shows an interaction between statins and reduced MACE risk, “once you go up to fit or highly fit, I’m not sure it matters,” Kokkinos said.

One potential limitation of the study by Kokkinos and colleagues is that the median age of the veterans was 59 years, so the interaction of statins, exercise, and risk for MACE later in life was not addressed in this study.

“I think it would have been similar; we had some people in their seventies and eighties. But, yes, we do not know this — I don’t have that data,” Kokkinos said.

Not a ‘One-Size-Fits-All’ Therapy

Asked to comment on the findings by Szilveszter and colleagues, Kokkinos said, “If you have some degree of CAD or a higher calcium score, then statins increase your survival rate.”

Kokkinos added that screening patients using coronary CT angiography makes sense. “Of course, the more you know about the severity of disease, the better off you are as a physician. As we get more and more technology, more high-resolution results, we are able to do that better and discriminate the different phenotypes.”

Regarding the controversial public health proposal that statins are so beneficial that they should be added to public water supplies, Kokkinos said, “I’ve heard that, but my research shows that we should try to have everyone exercise instead of putting statins in the drinking water.”

“Statins are not for everyone and should not be used as one-size-fits-all therapy,” he added. Instead, prescription of statins “should be treated more skeptically when it comes to people with no symptoms, no major coronary artery disease, or other risk factors.”

The JACC: Cardiovascular Imagingstudy was independently supported. Szilveszter, Abraço, and Kokkinos reported no relevant financial relationships.

Damian McNamara is a freelance contributor to Medscape Medical News. He worked full-time for Medscape and WebMD from 2018 to 2024. McNamara has a BA in chemistry and an MA in science, health, and environmental reporting/journalism. He works out of a home office in Miami, with a 100-pound chocolate lab known to snore under his desk during work hours.