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11th February 2011
Results from a Cochrane review supports previous evidence that statins reduce all-cause mortality, combined fatal and non-fatal endpoints (CHD, CV disease and stroke events) and revascularisation rates, when used for primary prevention in people at higher risk of CV disease. However, due to limitations in the evidence, the authors recommend a cautious approach when considering whether or not to prescribe statins for primary prevention in people with lower CV risk.
Level of evidence:
Level 1 (good quality patient-oriented evidence) according to the SORT criteria.
Action
Health professionals should continue to follow NICE guidance on lipid modification and type 2 diabetes. This Cochrane review supports the recommendations outlined in existing NICE guidance on primary prevention of cardiovascular (CV) disease. Simvastatin▼* 40mg/day is recommended as the first choice lipid lowering drug for primary prevention in adults who have a 20% or greater 10-year risk of developing CV disease. Patients need to be given information about their absolute risk of CV disease and the likely absolute benefits and harms of treatment in ways meaningful to them – NICE recommend the patient decision aid on statins found within the lipids eLearning materials of the NPC website.
*Note: The MHRA has advised that the black triangle (▼) refers to intensive monitoring being requested only when used in children and adolescents (10-17 years of age), in line with the recently licensed paediatric dosing recommendation.
What is the background to this?
Several large meta-analyses have highlighted the benefits of statins for people with a past history of CV disease (i.e. secondary prevention). However, the evidence is less clear for people without a past history of CV disease (i.e. primary prevention). Some systematic reviews (e.g. Brugts 2009, Mills 2008) have promoted the role of statins in primary prevention, while some authors have concluded that any assumed benefits of statins in secondary prevention trials should not be extrapolated to primary prevention populations.
The aim of this Cochrane review was to assess the benefits and harms of statins for the primary prevention of CV disease.
What does this study claim?
This was a systematic review of 14 RCTs (n=34,272). Eleven trials recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria). Statins significantly reduced all-cause mortality (risk ratio [RR] 0.83, 95% confidence interval [CI] 0.73 to 0.95), combined fatal and non-fatal CHD, CV disease and stroke events (RR 0.70, 95%CI 0.61 to 0.79), and revascularisation rates (RR 0.66, 95%CI 0.53 to 0.83). There was no clear evidence of any significant harm or, adverse events associated with statins. The authors conclude that there was limited evidence to suggest that statins may be cost effective and improve patient perceived quality of life in primary prevention.
So what?
This Cochrane review supports the recommendations outlined in existing NICE guidance on the primary prevention of CV disease. In people at high risk of CV events (i.e. 20% or greater 10-year risk of developing CVD), the authors conclude that it is likely that the benefits of statins are greater than any potential short term harms, although the long-term effects (over decades) remain unknown. A recent Lancet editorial also comments that the Cochrane review supports NICE guidance.
Despite the favourable findings, the authors of the Cochrane review recommend that any decision to use statins for primary prevention should be made cautiously and in light of an assessment of the patient’s overall CV risk profile. Widespread use of statins in people with low CV risk (i.e. below the NICE primary prevention threshold of 20% or greater 10-year risk of developing CVD) is not supported by the existing evidence. NICE recommends that people should be offered information about their absolute risk of CVD and about the absolute benefits and harms of an intervention over a 10-year period. This information should be in a form that:
− presents individualised risk and benefit scenarios
− presents the absolute risk of events numerically
− uses appropriate diagrams and text.
(See the NPC patient decision aid on statins)
Furthermore, the authors discuss some of the limitations of the published evidence for primary prevention, including the selective reporting of outcomes, inclusion of people with CV disease and inadequate reporting of adverse events (8 of the 14 trials reported no adverse events at all). Trials tended not to report single end points of CHD or stroke events, reflecting the small numbers of events and that they were powered for composite endpoints. Overall, populations in the review were white, male and middle aged; therefore the findings may not be generalisable to older people who may be at greater risk of adverse effects, and women, who may be at lower CV risk.
Design
Systematic review and meta-analysis of 14 RCTs with 16 trial arms, dating from 1994 to 2006.
Patients
34,272 men and women (aged >18 years) with no restrictions on total, LDL, or HDL cholesterol levels. Patient population in included studies was limited to <10% with a previous history of CV disease.
Intervention and comparison
Statins for at least 12 months versus placebo or usual care. Length of follow-up was at least 6 months. Drug treatments and interventions were accepted provided they were given to both intervention and control group.
Outcomes and results
Primary outcome measures:
| Outcome measure | RR (95%CI) |
| All-cause mortality | 0.83 (0.73 to 0.95) |
| Fatal and non-fatal CHD events | 0.72 (0.65 to 0.79) |
| Fatal and non-fatal CVD events | 0.74 (0.66 to 0.85) |
| Fatal and non-fatal stroke events | 0.78 (0.65 to 0.94) |
| Combined endpoint (fatal and non-fatal CHD, CHD and stroke events) | 0.70 (0.61 to 0.79) |
Secondary outcome measures:
| Outcome measure | RR (95%CI) |
| Revascularisation | 0.66 (0.53 to 0.83) |
| Adverse events | 0.99 (I 0.94 to 1.05) (not significant) |
| Total cholesterol | Net difference –0.89mmol/L (–1.20 to –0.57mmol/L) |
| LDL-cholesterol | Net difference –0.92mmol/L (–1.10 to –0.74mmol/L) |
| Quality of life | No reliable data |
| Costs | Insufficient data (only reported by one trial) |
Sponsorship
The review was conducted by Cochrane authors. 13 out of the 14 trials reviewed were pharmaceutical industry-sponsored.
More information can be found on the lipids section of NPC.
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Related PJ Online article: Are statins bad for you?