Statin side effects are more troubling than a new paper admits

A review published in the Lancet argues that the negative side effects of statins are widely exaggerated. (The paper, however, has its own flaws — see our expert analysis below).

The review, led by the Clinical Trial Service Unit at the University of Oxford, looked at data on 10,000 patients who were taking an average of 40mg of statins daily over a period of five years. It was found that within the sample population there were between 50 and 100 cases of negative side effects such as muscle pain or liver damage.

However, the drugs were found to lower cholesterol levels sufficiently to prevent over 1,000 ‘major cardiovascular events’ such as strokes and heart attacks in patients who had cardiovascular disease, and 500 in people who were merely at risk of the disease due to age or illness, out of the 10,000 patients looked at.

Crestor Statin Drug Pill

Another finding of the review is that people who know they are taking statins are more likely to report negative side effects. In randomised blind trials, the incident level was lower.

The study’s lead author, Professor Rory Collins, said: ‘Our review shows that the numbers of people who avoid heart attacks and strokes by taking statin therapy are very much larger than the numbers who have side effects with it.

‘In addition, whereas most of the side effects can be reversed with no residual effects by stopping the statin, the effects of a heart attack or stroke not being prevented are irreversible and can be devastating.

‘Consequently, there is a serious cost to public health from making misleading claims about high side effect rates that inappropriately dissuade people from taking statin therapy despite the proven benefits.’

Instant analysis
This comprehensive and elegantly written 30-page summary of the evidence appears at first sight to lay the statin controversy to rest once and for all. It does, however, raise several concerns.

First, the conflicts of interest of the principal author Professor Collins are impressive. The Cholesterol Treatment Trialists’ Collaboration (CTTC) which he heads has not only received millions of pounds in funding from pharmaceutical companies but also refuses to release its data for independent third-party scrutiny.

The co-authors of the review themselves contributed to the RCTs being reviewed. This is akin to getting architects who designed a building to then assess it for design and structural flaws. The long list of industry links revealed at the end of this paper is also concerning, as we know that trials funded by industry are more likely to reveal positive results My Pro Blog.

The results, though expressed clearly and unambiguously, are also incomplete in places.

‘Large-scale evidence from randomised trials shows that each 1 mmol/L reduction in LDL cholesterol with statin therapy produces a proportional reduction of about 25 per cent in the rate of major vascular events (coronary deaths, myocardial infarctions, strokes, and coronary revascularisations) during each year (after the first) that it continues to be taken. Consequently, lowering LDL cholesterol by 2 mmol/L reduces risk by about 45 per cent.’

In direct terms, ‘lowering LDL cholesterol … for about five years in 10,000 patients would typically prevent major vascular events in about 1,000 (10 per cent) patients at high risk of heart attacks and strokes (eg, secondary prevention) and 500 (five per cent) patients at lower risk (eg, primary prevention)’.

In other words, 90 per cent of patients with risk factors for cardiovascular disease, and 95 per cent of patients without, will gain no benefit from statin use over five years.



About the author

Rohit Shetty