Controversy around the use of statins for the primary prevention of cardiovascular disease is once again in the news, with a new analysis just published in the BMJ suggesting that statin use in low-risk patients “may be an example of low value care (having little benefit and potential to cause harm) in these patients and, in some cases, represent a waste of healthcare resources,” researchers conclude.

The researchers, who were led by Paula Byrne, PhD, National University of Ireland Galway, say there is uncertainty about whether the benefits of statins outweigh the harms for primary prevention and whether widespread statin use can be justified from a societal perspective.

Nevertheless, clinical guidelines have expanded the eligibility criteria over time, and in many countries the majority of people taking statins do so for primary prevention.

“We wanted to look at who is using statins and why, and investigate the benefits in the people who are actually taking them, particularly those who have not got established heart disease where there is debate as to the usefulness of statins,” Byrne explained.

For their analysis, the researchers examined the effects of changes to European guidelines on cardiovascular disease prevention from 1987 to 2016 using data from a national cohort of older people in Ireland.

“Of those aged over 50 in this database, 30% were using statins — two thirds for primary prevention,” Byrne said. “Three quarters of women on statins were taking them for primary prevention compared with just over half of men. As so many people are taking statins for primary prevention, we need to be really clear of their benefits in this population.”

Applying guideline recommendations from various times over the past 30 years to the Irish cohort, the researchers found that according to the 1987 guidelines 8% of their population would have been eligible for statins, but by 2016 the guidelines were recommending much greater use of statins so that 61% of the cohort were eligible for the drugs. “That is a huge increase,” Byrne commented.

The researchers then went looking for what evidence there was to support use of statins in primary prevention patients.

“We found that although there have been many studies and meta-analyses of statin treatment there is little evidence separating out the primary and secondary populations,” Byrne noted.

They found three systematic overviews that reported on primary prevention patients separately — two reviews from the Cholesterol Treatment Trialists’ (CTT) Collaboration that were considered to be one dataset because they analyzed the same data; and two other reviews by Mora et al and Ray et al.

The researchers calculated that based on 1994 guideline recommendations for use of statins, the number needed to treat (NNT) to prevent one cardiovascular event in the primary prevention population was 40, which Byrne said was “quite a reasonable number.”

But when applying the 2016 guidelines to the data, they found an NNT of 400. “So we are getting far less bang for our buck with the 2016 guidelines,” Byrne noted.

“Some clinicians and patients may desire a reduction in risk of cardiovascular disease, regardless of whether the benefit is small,” the authors write. “For others, the impact of potential adverse effects heavily influences their decision making, and even modest estimates of harms caused by daily medication could negate the benefits of statins.”

But they point out that data on adverse effects from some of the relevant studies have not been made available for independent analysis, and there is a high level of uncertainty as to what the harms are.

“The CTT estimates that for every 10,000 patients treated with statins for 5 years, there would be five cases of myopathy, 50 to 100 new cases of diabetes, and five to 10 hemorrhagic strokes,” Byrne said.

“Other data has suggested that frequency of myopathy is much higher — at about 530 cases per 10,000 patients treated for 5 years,” she added. “Also, myopathy is a high bar for defining muscle symptoms — what a person thinks is muscle pain probably is muscle pain. We need access to the data so it can be independently scrutinized to try and estimate this more accurately.”


REFERENCE: Byrne et al: Statins for primary prevention of cardiovascular disease;