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【drug-news】Cochrane系统评价药厂资助的临床研究误
Cochrane review stirs controversy over statins in primary prevention
Jan 20, 2011 Sue Hughes
London, UK - A new Cochrane review has provoked controversy by concluding that there is not enough evidence to recommend the widespread use of statins in the primary prevention of heart disease [1].
The authors of the new Cochrane meta-analysis, led by Dr Fiona Taylor (London School of Hygiene and Tropical Medicine, UK), issued a press release questioning the benefit of statins in primary prevention and suggesting that the previous data showing benefit may have been biased by industry-funded studies. This has led to headlines in many UK newspapers saying that the drugs are being overused and that millions of people are needlessly exposing themselves to potential side effects.
This has angered researchers who have conducted other large statin meta-analyses, who say the drugs are beneficial, even in the lowest-risk individuals, and their risk of side effects is negligible. They maintain that the Cochrane reviewers have misrepresented the data, which they say could have serious negative consequences for many patients currently taking these agents.
The Cochrane authors reviewed data from 14 trials involving 34 272 patients. Outcomes in patients given statins were compared with outcomes in patients given placebos or usual care. Although results suggested that deaths were reduced on statins, the researchers say the effect is not large enough to justify the cost/effort and risk of adverse effects.
Senior author Dr Shah Ebrahim (South Asia Network for Chronic Disease, New Delhi, India) told heartwire that their review differed from others done in primary prevention in that it looked at just those at low risk, limiting the studies included to just those with populations where <10% had a previous history of CVD.
It is probably a real effect but it means a lot of people have to be treated to gain this small benefit.
Ebrahim commented to heartwire: "If you look at the hard end points of all deaths and coronary deaths, the effects are consistent with both benefit and with the play of chance. But importantly, the absolute benefits are really rather small—1000 people have to be treated for one year to prevent one death. It is probably a real effect, but it means a lot of people have to be treated to gain this small benefit. As we don't know the harms, it seems wrong-minded to me to treat everyone with a statin. In these circumstances, lifestyle changes and stopping smoking would be far preferable."
I object to the conclusions they have drawn from their review.
But Dr Colin Baigent (Clinical Trials Service Unit, Oxford, UK) commented to heartwire: "I object to the conclusions they have drawn from their review. They say there is not good evidence of benefit, but their own data show significant reductions in deaths and cardiac events." And Baigent further objects to the Cochrane authors' suggestion that harms are not known with statins. "They didn't show any increase in adverse events in their review, but they then say the benefit is not worth the risk. That doesn't make sense."
Cochrane results
The Cochrane review showed that in the eight trials that reported on total mortality, none of the individual trials showed strong evidence of a reduction in total mortality, but when the data were pooled, a relative risk reduction of 17% was observed with statin treatment. On combined fatal and nonfatal CHD events, nine trials reported on this end point, with four trials showing evidence of a reduction in this combined outcome, which was maintained in the pooled analysis, with a 28% relative reduction. Seven trials reported on fatal and nonfatal stroke, and on pooled analysis, statin treatment was associated with a 22% relative reduction.Cochrane review: Risk ratio of major events with statins in lower-risk primary-prevention patients
Outcome
Risk ratio (95% CI)
Total mortality
0.83 (0.73-0.95)
Fatal and nonfatal CHD events
0.72 (0.65-0.79)
Fatal and nonfatal stroke
0.78 (0.65-0.94)
No excess in combined adverse events, cancers, or specific biochemical markers were found.
The authors conclude: "This current systematic review highlights the shortcomings in the published trials of statins for primary prevention. Selective reporting and inclusion of people with cardiovascular disease in many of the trials . . . in previous reviews of [statins'] role in primary prevention make the evidence impossible to disentangle without individual patient data."
They say that in people at high risk of cardiovascular events (>20% 10-year risk), "it is likely that the benefits of statins are greater than potential short-term harms, although long-term effects (over decades) remain unknown." They conclude: "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."
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作者:admin@医学,生命科学 2011-02-23 02:34
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