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Heart Health, Explained

Statins: Do Cholesterol-Lowering Medications Reduce Heart Risks for Women?

Whether statin therapy to lower LDL or “bad” cholesterol is as effective in women as in men has been the subject of medical debate. Now, the results of a large international study that compared the effects of statin therapy between men and women show conclusively that statin treatment reduces risk of cardiovascular disease in women as well as in men. The study was published in The Lancet and publicized in Science Daily on Jan. 9, 2015.

Statin Therapy Q&A

Q: Why has there been uncertainty about whether statin therapy is of value for women, even though heart attacks and strokes are major risks for women just as they are for men?

A: Unfortunately, women have been underrepresented in studies of statins. In the 27 individual trials that were combined for the analysis we are discussing, only 27% of the participants were women. This low enrollment rate makes it difficult to draw any firm conclusions regarding the effectiveness of statins in preventing heart attacks and stroke events in women in any one individual trial, with the individual trial being the traditional way medical research is conducted and reported.

Q: How was this study conducted?

A: This new study was designed to overcome the uncertainty regarding the effects of statins in women in individual trials due to the small number of women participants. The present study combined the results of many smaller trials investigating the possible benefits of statins in prevention of heart attack and stroke events into one large analysis (meta-analysis), thereby greatly increasing the certainty of its conclusions by looking at a much larger number of subjects. The study combined the data from 27 trials, including 22 studies of statins compared with placebo, and 5 studies of higher dose compared to lower dose statins. This translated into information from 46,675 female subjects out of a total trial population of 174,149 patients. The results from female participants were compared with the male participants. Because the individual trials were all somewhat different in the types of patients they enrolled, and the exact medications differed as well, the researchers used statistical methods to ensure appropriate comparisons as much as possible.

Q: What, specifically, did the study results show about statin therapy for reducing the risk of cardiovascular disease in women?

A: The study showed the benefits of statins in preventing cardiovascular events were similar in women compared to men. Specifically, for every decrease of 40 mg/dl of LDL (bad cholesterol) when on treatment with a statin, the risk of major cardiovascular events was decreased by 16 percent in women and by 22 percent in men, which did not represent a statistically significant difference between the benefits in men and women. Total mortality was reduced with statins by 9 percent in women and 10 percent in men, again not statistically different between genders.

Reference: “Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials,” The Lancet, January 9, 2015.

Q: Are there ways women can reduce cardiovascular disease risks that do not involve statin therapy?

A: Yes. A healthy diet consisting of plenty of fruits and vegetables, whole grains and fish, and minimizing red meat, other animal fats, and junk food is one way. This leads to a lower rate of cardiovascular events. Low-fat dairy products can be part of a heart healthy diet. Olive and canola oil, and nuts are a heart healthy source of fats. Regular exercise and maintaining a healthy weight can also lower the risk of cardiovascular events. The American Heart Association recommends a minimum of 30 minutes of exercise a day, 5 days a week, such as brisk walking, or equivalent exercise. These measures should be thought of as complementary to statin therapy for people at high risk of cardiovascular events and not as substitutes for one or the other. The greatest reductions in cardiovascular risk in people at high risk for disease are achieved by both leading a healthy lifestyle and using certain medications as prescribed by your physician, including statins.

Reference: NEJM 2013; 368: 1279-1290.

Q: In 2013, the American College of Cardiology and the American Heart Association appeared to abandon LDL cholesterol levels as targets for statin therapy. Instead, they recommended an “Omnibus Risk Estimator” as part of an overall approach to consider “the whole patient.” How can women make sense of the results of this new study in The Lancet in light of the 2013 guidelines?

A: What the new guidelines point out, and this new study supports, is that there is no LDL level, as the old guidelines implied, at which a person who is otherwise at high risk for cardiovascular events is “safe’ from risk. According to the old guidelines, if your LDL level was below a certain level, no statin treatment was recommended. However, multiple studies, including many of the studies included in this new analysis, have shown that, even for patients starting out at LDL levels where no treatment was recommended by the old guidelines, there is as much benefit from statins in terms of reduction of cardiovascular events as for patients with LDLs above the old guidelines’ treatment threshold. This holds true for patients who were otherwise at high risk for cardiovascular events because they were diabetic, had a known history of coronary artery disease, or had multiple risk factors for cardiovascular disease. In fact, no range of LDLs could be found, in otherwise high risk patients, in whom there was not a benefit from statins. That doesn’t mean, though, that LDL isn’t important. What appears to best predict the degree of reduction in cardiovascular events is not a particular LDL level before or after treatment, but rather the amount the LDL drops on treatment from whatever the starting LDL level happens to be. The current study we are discussing shows a predictable drop in cardiovascular risk the more the LDL decreases on treatment (16 percent decrease in risk for every decrease of 40 mg/dl of LDL in women). The most reliable way to achieve the greatest decrease in LDL is taking the highest safe dose of the most potent statin available. Hence, the new guidelines recommend high doses of the strongest statins (atorvastatin and rosuvastatin) for patients at the highest risk of cardiovascular events, regardless of their baseline LDL.

Resource: American College of Cardiology, American Heart Association – 2013 Prevention Guideline Tools and Risk Calculator


Answers to your questions on timely topics in cardiac care to help make sense of research reports in the media. The series includes questions on your heart and the effect of medications, exercise, diet, and hormones.

Team Specialist

Peter Amsterdam, MD, FACC Interventional Cardiology Medical Director, Heart Disease Management at Grant Medical Center OhioHealth Healthcare System, Columbus, Ohio

Q&A Editor

Teresa Caulin-Glaser, MD, FACC, FAACVPR System Vice President, Heart & Vascular Services OhioHealth Healthcare System, Columbus, Ohio

Heart Health Explained is a collaboration of Women’s Health Research at Yale and the OhioHealth Healthcare System, a nationally recognized not-for-profit organization with providers across 46 counties, offering a holistic approach to prevention, treatment and rehabilitation of heart disease. OhioHealth is staffed by physicians, psychologists, nutritionists and nurses who answer the questions of the moment on heart and vascular health.

The information provided here may help you make more informed choices. However, it is not a substitute for an individualized medical opinion or diagnosis, and everyone should always consult with their personal physicians to make decisions about their condition or treatment.