Cholesterol Guidelines - Evidence Based?

The controversy over the appropriateness of using HMG CoA reductase inhibitors or "statin" drugs (e.g., atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin) to treat high blood cholesterol levels in hopes of to preventing the development of heart and vascular disease just heated up.

Drs J Abrahmson and JM Wright published an interesting article in The Lancet on their evaluation of guidelines for the treatment of hyperlipidemia:

For adults aged between 30 and 80 years old who already have occlusive vascular disease, statins confer a total and cardiovascular mortality benefit and are not controversial.

The controversy involves this question: which people without evident occlusive vascular disease (true primary prevention) should be offered statins? With about three-quarters of those taking statins in this category, the answer has huge economic and health implications. In formulating recommendations for primary prevention, why do authors of guidelines not rely on the data that already exist from the primary prevention trials?

The authors argue that current guidelines are an extrapolation of secondary prevention trials, or data combined from secondary and primary prevention trials, and not based on randomized trials of just primary prevention in the hyperlipidemia literature. To establish a basis for their concerns, they performed a retrospective analysis of the data from primary prevention trials (which they admit were not perfect because some of the patients had known vascular disease) and discovered the following:

We used two outcomes to estimate overall benefit (benefit minus harm): total mortality and total serious adverse events (SAEs). Total mortality was not reduced by statins (relative risk 0·95, 95% CI 0·89–1·01). In the two trials that reported total SAEs, such events were not reduced by statins (1·01, 0·97–1·05) (data on SAEs from the other trials were not reported). The frequency of cardiovascular events, a less encompassing outcome, was reduced by statins (relative risk 0·82, 0·77–0·87). However, the absolute risk reduction of 1·5% is small and means that 67 people have to be treated for 5 years to prevent one such event. Further analysis revealed that the benefit might be limited to high-risk men aged 30–69 years. Statins did not reduce total coronary heart disease events in 10,990 women in these primary prevention trials (relative risk 0·98, 0·85–1·12). Similarly, in 3239 men and women older than 69 years, statins did not reduce total cardiovascular events (relative risk 0·94, 0·77–1·15).

There has already been interesting commentary on this subject, unfortunately it is by an individual who also wants to sell his book. Nonetheless, there is a large monetary incentive for the pharmaceutical industry to promote statins to the general population. One is left wondering if there could be a subgroup of asymptomatic individuals who really don’t need primary prevention treatment of hyperlipidemia, or if there are individuals in whom the risks of drug side effects exceeds the reward of primary prevention therapy.

With studies like this, there is no question that patients can become confused. Should I stop my statin drug? What drug is best?

The answer here is simple: ask your doctor. This article is not justification for discontinuation of statins, especially since it, too, is flawed by the retrospective nature of their data. Rather, the authors' point appears to expose an area that should be studied further to assure our ounce of prevention is not worse than a pound of the disease.

-Wes

Reference: J Abramson and JM Wright ,”Are lipid-lowering guidelines evidence-based?” Lancet, 20-26 Jan 2007, Vol 369, Issue 9557, pp 168-169.