Richard Smith: Statin arguments

Richard SmithA Spanish friend who is a pharmacist and basic scientist and with whom I have a spirited argument over the polypill has emailed me to gloat over the press reports derived from a Cochrane review that statins provide no benefit for healthy people. She believes that healthy living will suffice for fending off heart attacks and strokes and that the polypill is a dangerous delusion.

Friends like her think me very confused in that I’m rejoicing in finally taking the polypill seven years after praising it to the heavens in the BMJ but am at the same time a prophet of demedicalisation, contributing to a proposed television programme on “The town that gave up medicine,” a guzzler of porridge every morning without either salt or sugar, and well through a month without alcohol and with three runs and 70 000 steps a week.

My enthusiasm for the polypill undiminished by the press reports of the hopelessness of statins for the healthy, I replied hotly to my gloating friend.

Dear Gloater,

Did you actually read the review rather than the press reports? Here are two bits from the abstract:

“Main results
Fourteen randomised control trials (16 trial arms; 34,272 participants) were included. Eleven trials recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria). All-cause mortality was reduced by statins (RR 0.83, 95% CI
0.73 to 0.95) as was combined fatal and non-fatal CVD endpoints (RR 0.70, 95% CI 0.61 to 0.79). Benefits were also seen in the reduction of revascularisation rates (RR 0.66, 95% CI 0.53 to 0.83). Total cholesterol and LDL cholesterol were reduced in all trials but there was evidence of heterogeneity of effects. There was no clear evidence of any significant harm caused by statin prescription or of effects on patient quality of life.

Authors’ conclusions
Although reductions in all-cause mortality, composite endpoints and revascularisations were found with no excess of adverse events, there was evidence of selective reporting of outcomes, failure to report adverse events and inclusion of people with cardiovascular disease. Only limited evidence showed that primary prevention with statins may be cost effective and improve patient quality of life. Caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk.”

In other words, statins did reduce mortality and CVD events dramatically, as we would expect.

George (Davey-Smith] and Shah [Ebrahim]–two of the authors of the review, both of them friends of mine, paid up iconoclasts, and in the case of George an unreconstructed Trotskyist (or something equally ardently left wing) –draw some dubious conclusions. Let me address these:

1. Selective reporting: sadly this is a fact of life and could be used to undermine confidence in all drug trials because virtually all drug trials are funded by drug companies. Most drug trials have effect sizes much smaller than those that the review reports.

2. Failure to report adverse effects: again this is very common. But RCTs are not the best way to assess side effects because of the relatively small numbers in trials and the short follow up. As you know, millions of people across the world have now taken statins for years and side effects are well known and minimal.

3. Inclusion of people with cardiovascular disease: This phrase is disingenuous as you don’t really “have or not have CVD.” As Geoffrey Rose, the great epidemiologist said, there is no disease that you have or don’t have–apart perhaps from sudden death. Are two people, one of whom has angina and another a 25% risk of a heart attack or stroke in the next 10 years, very different? I think not.

4. Cost effectiveness. That statins are now coming off patent will surely transform this picture. We know that the polypill can be manufactured for as little as a dollar a month.

5. Quality of life. This is absence of evidence rather than evidence of ineffectiveness. The severe deterioration in quality of life comes from having a stroke.

So I don’t think that this review really changes anything.

Best wishes
Richard

Competing interest: RS is the unpaid chair of the Cochrane Library Oversight Committee and is taking the polypill as part of a double blind randomised cross over trial after two years of taking the individual drugs. As he’s not getting up to pee at nights he thinks he’s on the placebo.

  • And what about the ladies? I don’t mean to start a boring discussion about the pros and cons of subgroup analysis but… So many heart drug studies do not separate results by gender. Should our lot be so united to that of men? Especially when we have this annoying habit of living longer. Here in the U.S., 78% of female deaths from heart disease occur after the age of 75. (I got this stat from the CDC last year, but have yet to see it in any “women and heart disease awareness” campaigns.) And should a 48 kg woman (yes there are some in the U.S.) be given the same dose as a 150 kg man, as is often the case in many heart drug trials?

  • Vos

    Richard, I'm relieved you think you're on placebo: we want you around for a while!

    About statins and reduced mortality: for women of any age and men over age ~65ish, that is a sad myth, supported by making a smoothie of the 'any patient data' including some large trials that showed some temporary mortality benefit in younger males. The lack of a female mortality or even second MI benefit is a fact certain as per 2 meta-analysis, JAMA and JACC no less.

    ALL statin benefit may well result from their undisputed effect of imitating nitroglycerin**). Therefore, less angina [-41% in ASCOT] and thus fewer reported non fatal MI's, and fewer sent to the 'balloon lab', the 50% of the 'benefit' found in JUPITER. That massive trial found no benefit in cardiovascular deaths [but there was a chance finding of less cancer deaths, but identical 'new' cancers].

    The links to references and my take are at the end of this page:
    http://www.health-heart.org/au

    You may have noted that Ebrahim et al did not split out women, a group where mortality has been proven not to exist. Regards, Eddie Vos

    **) similarly, Vioxx: less pain and thus fewer knee 'revascularizations' over a typical study period as used for statins.

  • Vos

    One of the meta-analysis I referred to had 20,000 women and NO mortality benefit after many years on statin. How many women more does it take? Well, JUPITER added about 6000 and the ONLY benefit was in fewer revascularizations [balloons] in women. Zip in any other departments including deaths or heart attacks or strokes.

    Richard is right, statins are getting cheaper [$4.95/year for lovastatin in some clountries]. My problem: the 2 largest lovastatin trials ended with more deaths even in largely male populations [EXCEL and TexCAPS trials].

  • Ian Scobie

    I was sure the noun was 'deterioration'

  • jhwalker

    Thanks for pointing that out out Ian, I have corrected the error in the blog.
    Juliet