Statin Therapy Benefits Patients with Highest Genetic Risk of Heart Attack

Which patients benefit the most from statins?

authors Lynne Jeter

Widely-used statin therapy provides the most benefit to patients with the highest genetic risk of heart attack, according to Nathan O. Stitziel, MD, PhD, a cardiologist and human geneticist at Washington University in St. Louis, and co-author of a study published earlier this year that’s receiving national buzz.

“There’s no ongoing study in the same realm, concerning statins and genetic risk,” said Stitziel. “Interestingly, the study isn’t so much about statins, but rather the use of genetics as a method for identifying patients at risk and those who could potentially benefit from primary prevention therapy. It just turns out that statins are the best means we have as a way to reduce heart attacks.”

The research team included investigators studying 49,000 patients across five studies at Brigham and Women’s Hospital, Harvard Medical School, Massachusetts General Hospital and Washington University. Using a relatively straightforward genetic analysis, the team assessed heart attack risk independently of traditional risk factors – age, sex, cholesterol levels, smoking history, and family history – and whether the patient has diabetes. They discovered that individuals in the high genetic risk category have a 70 percent higher risk of heart attacks, compared with those at lowest genetic risk. They also pointed out that statin therapy results in a 13 percent reduction in risk in the low genetic-risk group, a 29 percent reduction in the intermediate group, and a 48 percent reduction in the high-risk group.

Results of the 2015 published study, “Genetic Risk, Coronary Heart Disease Events, and the Clinical Benefit of Statin Therapy: An Analysis of Primary and Secondary Prevention Trials,” differ from past research, which has consistently shown that statins provide about the same relative risk reduction — 30-45 percent, depending on dosage — across all categories of patients, said Stitziel.


Study Specifics

Investigators analyzed each patient’s DNA code for the 27 genome positions and risk of coronary heart disease to calculate the genetic-risk score.

Individually, many genome locations are linked to a minor increase in risk while the high-risk letter may be quite common, explained Stitziel.

“For example, a T instead of a G in a particular spot may be associated with a 6 percent increase in risk, and that T may be present in 70 percent of the population,” he explained. “But combined, the risk score appears to become a clinically meaningful measure of coronary heart disease risk.”

Stitziel pointed out the 27 markers do not change with age or lifestyle. Theoretically, a person at high risk of developing coronary heart disease could be identified early, before traditional measures of the disease would be detected with a doctor’s physical exam or routine blood work.


Too Liberal?

The multi-institutional study has spurred national debate over the “liberal prescribing” of statin drugs. Two years ago, the American College of Cardiology (ACC) and the American Heart Association (AHA) changed the guidelines for statin therapy, dramatically increasing the number of patients recommended to take it.

“The new AHA/ACC guidelines could put half of all adults in this country on statins for life … totally absurd,” wrote David Williams, MD, in “Statins: Separating Fact from Fiction” in a 2014 edition of Alternatives.

Stitziel acknowledged the ongoing debate over which individuals should be allocated statin therapy to prevent a first heart attack. “Some have said we should be treating more people,” he said, “while others say we need to treat fewer.”

That’s where precision medicine comes into play, Stitziel emphasized.

“It’s another approach to identify people at high risk and preferentially prescribe statin therapy to those individuals,” he said. “Genetics appears to be one way to identify high-risk patients.”

Unfortunately, this particular genetic analysis isn’t yet available to patients.

“More research is needed to validate the findings before such a test could be developed for clinical use,” said Stitziel. “The bigger issue behind it is that insurers would need to start paying, and obviously that takes lots of decisions beyond my world of research.”



  • “Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials,” in The Lancet:
  • Dr. Nathan O. Stitziel:
  • Brigham and Women’s Hospital:
  • Harvard Medical School:
  • Massachusetts General Hospital:
  • Dr. David Williams:
  • Washington University School of Medicine:


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