Do statins cut risk for the healthy?

Researchers say that “statins cut the risk of heart attacks by 30% even in healthy people” and lower the chance of dying from any cause by 12%, the Daily Mail reported. It said that the drugs are currently only given to people who are at significant risk of heart attack or stroke. The latest review of the research has renewed the ongoing debate over whether everyone over 50 should be prescribed statins.

The news story is based on a large systematic review of 10 trials, which pooled the results of over 70,000 people. It found that, over an average 4.1 years, statins reduced the risk of death by any cause, as well as from heart attacks and strokes, in people who had not been diagnosed with cardiovascular disease but who had the risk factors for it.

As all these people had some degree of cardiovascular risk, such as high blood pressure, high cholesterol or diabetes, describing them as “healthy” does not clearly portray their risk status. However, these important findings indicate that a number of people could benefit from long-term statin use. As the authors say, identifying the people with risk factors could be a challenge and giving statins to everyone over a certain age would have significant cost and safety implications.

Where did the story come from?

The research was carried out by Dr JJ Brugts from the Department of Cardiology, Erasmus MC Thoraxcenter, Rotterdam, and colleagues from other international institutions. Several of the authors had affiliations with various pharmaceutical companies. The study was published in the peer-reviewed British Medical Journal .

What kind of scientific study was this?

This systematic review investigated whether statins reduce deaths from any cause and reduce the risk of major coronary and cerebrovascular events (such as heart attacks and strokes) in people who have cardiovascular risk factors but have not been diagnosed with cardiovascular disease. It also looked at whether gender, age (above or below 65) and diabetes have an effect.

The researchers carried out a search of several medical databases to identify trials that compared any statin with a control or placebo drug and their effects on “cardiovascular disease”, “coronary heart disease”, “cerebrovascular disease”, “myocardial infarction” or “cholesterol”. The trials were at least a year long and at least 80% of the participants had no existing cardiovascular disease. Following a quality assessment, 10 trials met the inclusion criteria.

The main outcome that the researchers examined in their analyses was death from any cause, followed by death from heart disease and stroke. Where data was available, they looked at these outcomes in several subgroups: men, women, the young, the elderly and people with diabetes. Where possible, results from the separate studies were pooled in meta-analysis.

What were the results of the study?

Of the 10 studies, two trials examined people with high cholesterol (one of which was in men only), one was in elderly people with cardiovascular risk factors, two were in people with high blood pressure and other risk factors, three were in people with diabetes, one was in people with low cholesterol and one was in people without vascular disease.

In total, the 10 studies included 70,388 participants who had been randomly allocated to receive a statin (35,138 participants) or a control pill (35,250). The number of participants in the trials ranged from 1,905 to 17,802. The average age of participants was 63 and the average length of follow-up was 4.1 years. Overall, 23% of the participants had diabetes. The different trials contained varying numbers of people with other risk factors, such as smoking, BMI, blood pressure and cholesterol.

During follow-up, 5.1% (1,725) of the statin group died compared with 5.7% (1,925) of the control group. Statin treatment significantly reduced the risk of death from any cause by 12% (odds ratio [OR] 0.88, 95% confidence interval [CI] 0.81 to 0.96). During this time, 4.1% of the statin group had a major coronary event, such as a heart attack, compared with 5.4% of the control group. In addition, 1.9% of the statin group had a major cerebrovascular event compared to 2.3% of the control group. Therefore, risk of any major coronary event, such as a heart attack, was 30% lower in the statin group (OR 0.70, 95% CI 0.61 to 0.81) and risk of stroke was 19% lower (OR 0.81, 95% CI 0.71 to 0.93).

Analysis of the subgroups (men, women, young, elderly and people with diabetes) showed that statins did not affect risk differently in any particular group.

What interpretations did the researchers draw from these results?

The researchers concluded that, in patients without established cardiovascular disease but with cardiovascular risk factors, statin use was associated with significantly improved survival and significant reductions in the risk of major cardiovascular events, such as heart attack and stroke.

What does the NHS Knowledge Service make of this study?

This large and thorough review of 10 trials found that, over an average follow-up of 4.1 years, statins significantly reduced the risk of death from any cause as well as the risk of heart attacks and strokes in people without cardiovascular disease but who had risk factors.

These are important findings and they should be interpreted accurately:

• When combining the results of different trials, there is always some degree of limitation which arises from differences between the trials. These include different populations, different trial drugs, different concurrent use of other medications, different methods of assessing outcomes and different length of follow-up. In particular, the participants of the different trials are likely to have had a highly varied level of cardiovascular risk. As the authors acknowledge, in three of the trials that they included, a small proportion of the participants had existing cardiovascular disease.
• Although the majority of study participants did not have existing cardiovascular disease, they all had cardiovascular risk factors (which varied depending on the trial). Therefore, although some of the newspapers suggest that statins should be given to “all” or “healthy” people above a certain age, this is not strictly the case. If people have existing cardiovascular risk factors, it seems plausible that reduction of one of them, such as cholesterol, will influence risk in some way. How much risk is reduced may depend on the type of risk factors that people have, which this review was not able to examine.

These findings show that a number of people could benefit from long-term statin use. However, as the authors say, identifying people with risk factors could be a challenge. Administering statins to everyone over a certain age in a ‘cover all’ approach has significant cost and safety implications.