Monday, 7 January 2013

Ben Goldacre 'Bad Pharma' - Cochrane 2011 report 'Statins for the primary prevention of cardiovascular disease'

reposted from:
crabsallover highlightskey pointscomments / links.

Ben Goldacres' 'Bad Pharma' mentions Cochrane as a independent systematic reviewer of trial results.

I blogged about The Lancets review of the Cochrane systematic study 'Statins for the primary prevention of cardiovascular disease' in January 2011 but until now I've not looked at the original Cochrane review.

The Cochrane website gives the 2011 Abstract, full Article and previous versions with free pdf downloads.



Reducing high blood cholesterol, a risk factor for cardiovascular disease (CVD) events in people with and without a past history of coronary heart disease (CHD) is an important goal of pharmacotherapy. Statins are the first-choice agents. Previous reviews of the effects of statins have highlighted their benefits in people with coronary artery disease. The case for primary prevention, however, is less clear.


To assess the effects, both harms and benefits, of statins in people with no history of CVD.

Search methods

To avoid duplication of effort, we checked reference lists of previous systematic reviews. We searched the Cochrane Central Register of Controlled Trials (Issue 1, 2007), MEDLINE (2001 to March 2007) and EMBASE (2003 to March 2007). There were no language restrictions.

Selection criteria

Randomised controlled trials of statins with minimum duration of one year and follow-up of six months, in adults with no restrictions on their total low density lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol levels, and where 10% or less had a history of CVD, were included.

Data collection and analysis

Two authors independently selected studies for inclusion and extracted data. Outcomes included all cause mortality, fatal and non-fatal CHD, CVD and stroke events, combined endpoints (fatal and non-fatal CHD, CVD and stroke events), change in blood total cholesterol concentration, revascularisation, adverse events, quality of life and costs. Relative risk (RR) was calculated for dichotomous data, and for continuous data pooled weighted mean differences (with 95% confidence intervals) were calculated.

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 0.84, 95% CI 0.73 to 0.96) 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

Reductions in all-cause mortality, major vascular events and revascularisations were found with no excess of cancers or muscle pain among people without evidence of cardiovascular disease treated with statins.  Other potential adverse events were not reported and some trials included 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.

Plain language summary

Statins for the primary prevention of cardiovascular disease

Cardiovascular disease (CVD) is ranked as the number one cause of mortality and is a major cause of morbidity world wide. Reducing high blood cholesterol which is a risk factor for CVD events is an important goal of medical treatment. Statins are the first-choice agents. Since the early statin trials were reported, several reviews of the effects of statins have been published highlighting their benefits particularly in people with a past history of CVD. However for people without a past history of CVD (primary prevention), the evidence is less clear. The aim of this systematic review is to assess the effects, both in terms of benefits and harms of statins for the primary prevention of CVD. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE until 2007. We found 14 randomised control trials with 16 trial arms (34,272 patients) dating from 1994 to 2006. All were randomised control trials comparing statins with usual care or placebo. Duration of treatment was minimum one year and with follow up of a minimum of six months. All cause mortality. coronary heart disease and stroke events were reduced with the use of statins as was the need for revascularisations. Statin treatment reduced blood cholesterol. Taking statins did not increase the risk of adverse effects such as cancer. and few trials reported on costs or quality of life. This current systematic review highlights the shortcomings in the published trials and we recommend that caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk.

Full Report

Very detailed. A Key paragraph is:-

On the basis of our systematic review and these recent meta-analyses, it is clear that any decision to use statins for primary prevention should be made cautiously and in the light of an assessment of the patient’s overall cardiovascular risk profile.  Widespread use of statins in people at low risk of cardiovascular events - below a 1% annual all-cause mortality risk or an annual CVD event rate of below 2% observed in the control groups in the trials considered here - is not supported by the existing evidence. Furthermore, the tendency of trial protocols to remove patients suffering with co-morbidities limits their generalisability to typical patient populations in whom decisions to prescribe statins have to made.

Further analysis of this report and the CTT 2012 report is required to be made by crabsallover.

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