It was the latest in a long stream of scare stories. ‘Statins DOUBLE the risk of diabetes,’ said the headlines. In fact, it has been known for some time that statin drugs increase the risk of diabetes. The increase in risk is modest — about 10 per cent. To put this into perspective, 250 people would need to be treated with statins for one case of diabetes to be identified. Many argue that this is an acceptable trade-off, given that the benefits of statins vastly outweigh the risks.
So, the benefits. High-quality trials have established that statins significantly decrease the risks of heart attacks, strokes and death among patients who have previously survived a heart attack or a stroke. (This phenomenon is known as ‘secondary prevention’.) For heart attack survivors, being put on statins reduces mortality risk by 30 per cent. For patients with pre-existing cardiovascular disease, the risk of a stroke is reduced by 25 per cent.
Not only that, but statins are being investigated for their utility as a treatment for cancer — in the case of ovarian cancer they may contribute to survival — and as a preventative measure in dementia.
The Cholesterol Treatment Trialists (CTT) collaboration, led by Sir Rory Collins, published a meta-analysis proving the benefits of statins in patients at low risk of vascular disease — ie, those who had never suffered a heart attack or stroke. These findings were incorporated into a Cochrane Collaboration review and a NICE guideline which suggested that patients with a 10-year risk of cardiovascular disease of 10 per cent or less should be prescribed statins, in contrast to previous guidance that advocated a 20 per cent cut-off.
So there we have it. An excellent family of drugs, proven efficacy at preventing cardiovascular events at both the primary and secondary levels, with robust data leading the way and an incidence of side effects that is lower than that of everyday drugs and a consensus among all the people that matter. Case closed I believe.
Or is it?
There are many sceptics in the medical profession of the idea that one should be medicating the otherwise healthy. Two-thirds of GPs, for instance, have chosen not to follow the new guidance.
The problem is that while statins have been proved incontrovertibly to be invaluable as part of secondary prevention, the data surrounding primary prevention is controversial. The gains are modest: 140 people with a five-year risk of less than 10 per cent need to be treated with statins for five years to prevent one heart attack or stroke. There is also no reduction in overall mortality or serious adverse events — and all the while patients are exposed to the side effects of the drugs.
Reported side effects of statins include trivialities like myopathy, rhabdomyolosis, diabetes, liver dysfunction, acute renal failure and cataracts, cognitive symptoms, neuropathy and sexual dysfunction, decreased energy and exertional fatigue, and psychiatric symptoms including depression, memory loss, confusion, and aggressive reactions. Additional side effects may paradoxically include a higher risk of breast cancer.
How common are these side effects? According to Professor Collins, the incidence is nine per cent (not the 18-20 per cent rate quoted in the BMJ and later corrected). But his analysis was restricted only to cardiovascular and potential cancer-causing side effects, not the full spectrum. This changes the picture substantially.
It is astounding, too, that the meta-analysis which paved the way for a NICE guideline is based on data that isn’t available for peer review or outside scrutiny. One wonders if this is an impediment to transparency and scientific integrity, especially given the fact that industry-sponsored trials are more likely to report positive results and lower side effect profiles than non-industry sponsored trials. The era of ’eminence-based medicine’ was supposed to have passed but is apparently alive and well.
Are there any options for those wanting to lower their risks of vascular disease without having to take a drug? No direct trials of statins alone versus lifestyle modification in otherwise healthy individuals have been done (and in my mind will never be done as no one will fund them), but evidence suggests that lifestyle modification can have profound effects on risk.
Statins work by decreasing the synthesis of cholesterol via inhibition of the enzyme HMG-CoA reductase, but they also have a significant anti-inflammatory effect which may explain the reduction in risk seen in those with pre-existing cardiac disease.
By some strange coincidence, a low-carbohydrate diet has the same effect on cholesterol as well as vascular inflammation.
Consuming nuts, extra virgin olive oil and fatty fish all have a powerful effect on risk. Evidence for these are found in the DART trial (29 per cent reduction in all-cause mortality in patients surviving a heart attack who consume fatty fish), the GISSI Prevention Trial (supplementing Omega-3 fatty acids significantly reduced all-cause and cardiovascular mortality in heart attack survivors) and the PREDIMED trial (energy unrestricted diet supplemented with extra virgin olive oil or nuts achieved a 30 per cent reduction in major cardiovascular events in patients free of vascular disease).
Patients need to be aware that the ‘evidence’ for statins for primary prevention is controversial. Guidelines are often far from the final word. In the case of the statins guidelines, one also has to wonder about outside influence. Eight out of the 12 members of the guideline committee had ties to the drug industry — a surprising coincidence. Merely announcing a conflict of interest does not magically result in a loss of bias.
For secondary prevention, statins indisputably have their place. For primary prevention, my opinion is that evidence-based lifestyle modifications should be undertaken, with recourse to drugs as the last resort. If you’re sceptical, just ask all the lucky people who have experienced the side effects.