Strength of evidence for perioperative use of statins to reduce cardiovascular risk: systematic review of controlled studies
BMJ 2006; 333 doi: https://doi.org/10.1136/bmj.39006.531146.BE (Published 30 November 2006) Cite this as: BMJ 2006;333:1149
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Kapoor et al. highlight that although evidence may suggest that the administration of statins peri-operatively is associated with lower rates of acute coronary syndromes and death (1) it is important to realise that this effect is predominantly seen in patients who would benefit from long term statin therapy anyway. Following several recent trials (2) and the recent reform of GP funding, prescribing rates in ‘at risk’ patients are improving markedly(3)
They also comment on the current lack of prospective data due to constraints on trial design: very large numbers are required to both ascertain the time and method of administration and to prove a universally beneficial effect in an unselected population.
It is worth noting that these trials are reminiscent of data regarding the perioperative use of beta-blockers which initially claimed similar outcomes for which there still remains no conclusive evidence(4).
(1) Kapoor et al., Strength of evidence for perioperative use of statins to reduce cardiovascular risk: systematic review of controlled studies. BMJ Dec 2006;333:1149
(2) Pederson et al., Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S) Circulation. 1998 Apr 21;97(15):1436-9.
(3) NHS Prescription Payment Authority, Update On Growth In Prescription Volume And Cost Year To June 2006 http://www.ppa.nhs.uk/pdfs/publications/SMT_V&C_report_200606.pdf (accessed 6th Dec 2006)
(4) Mangano et al., Effect of Atenolol of Mortality and Cardiovascular Morbidity after Noncardiac Surgery, N Engl J Med 1996; 335:1713-1721.
Competing interests: None declared
Competing interests: No competing interests
Kapoor, et al.(1) carried out a systematic review to determine the strength of evidence for using statins during the perioperative period to reduce the risk of cardiovascular events. Owing to methodological heterogeneity among studies, they carried out a meta-analysis of methodologically similar studies (e.g., all randomised trials or all cohort studies).
Regarding perioperative death or acute coronary syndrome, pooling the data from all 13 cohort studies gave a summary odds ratio of 0.70 (95% confidence interval 0.57 to 0.87) with statin use (text and fig 2 of the original article). Certainly, these 13 studies were methodologically similar because of all cohorts. Obvious between-study heterogeneity concerning types of surgery, however, was present in the pooled estimate derived from these 13 cohort studies.
The 13 studies pooled by Kapoor, et al. included both 10 cohorts of non-cardiac surgery and 3 cohorts of cardiac surgery. The pooled odds ratio from the 10 studies of non-cardiac surgery was 0.70 (0.53 to 0.91) (fig 2 of the original article). Furthermore, these 10 cohorts of non-cardiac surgery included 6 studies of non-carotid vascular surgery (e.g., repair of abdominal aortic aneurysm, aortic femoral bypass, and infrainguinal revascularization), 2 studies of carotid endarterectomy, 1 study of both carotid and non-carotid vascular surgery, and 1 study of thoracic surgery. Pooling the data from the homogenous 6 studies of non-carotid vascular surgery (380 events in 4865 patients) gave a summary odds ratio of 0.74 (0.54 to 1.01) with statin use (calculated by us). Therefore, routine administration of statins does not reduce perioperative cardiovascular risk in non-carotid vascular surgery.
1 Kapoor AS, Kanji H, Buckingham J, Devereaux PJ, McAlister FA. Strength of evidence for perioperative use of statins to reduce cardiovascular risk: systematic review of controlled studies. BMJ, doi:10.1136/bmj. 39006.531146.BE (published 6 November 2006).
Competing interests: None declared
Competing interests: No competing interests
The importance of the predicted cardiovascular risk when designing peri-operative statin trials
The recent meta-analysis of the efficacy of perioperative statins by Kapoor et al concludes that the evidence base for the use of these drugs is inadequate to recommend their routine use. The incidence of major cardiovascular complications following noncardiac surgery is of paramount importance when considering the appropriate implementation of peri- operative medical therapy, such as beta-blockade. The work presented by Kapoor et al1 allows us to illustrate the same principle concerning peri- operative statin therapy. In our original pharmaco-economic analysis of peri-operative statins where the control group had a major cardiovascular complication rate of 15.5% and a number-needed-to-treat (NNT) of 15, peri- operative statins resulted in an incremental cost of £664.70 per major cardiovascular complication avoided.2 If the same pharmaco-economic methodology is applied to the data provided by Kapoor et al1 of the cohort studies which reported both death and acute coronary syndromes, we find that the incidence of major cardiovascular complications in the control group is 6.3% with a NNT of 48, resulting in an incremental cost of £5961.34 per cardiovascular complication avoided. As conclusive randomised evidence on the efficacy of peri-operative statins does not exist,1 this pharmaco-economic analysis illustrates the importance of considering patients of appropriate predicted cardiovascular risk when designing peri- operative statin trials. Our analysis was based on a complication rate of 15.5% compared with the much lower rate reported by Kapoor et al. Possibly analysis based on numerical risk scoring would allow appropriate patients to be more clearly identified.
1. Kapoor AS, Kanji H, Buckingham J, Devereaux PJ, McAlister FA. Strength of evidence for perioperative use of statins to reduce cardiovascular risk: systematic review of controlled studies. BMJ 2006;333(7579):1149.
2. Biccard BM, Sear JW, Foex P. The pharmaco-economics of peri- operative statin therapy. Anaesthesia 2005;60(11):1059-63.
Competing interests: None declared
Competing interests: No competing interests