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Preoperative statins and effects on mortality
In many well designed studies, 3-HMG coenzyme A reductase inhibitors (also known as “statins”) have been shown to effectively lower serum cholesterol, slow the formation of atherosclerotic occlusive disease, and reduce the risks of death, myocardial infarction, stroke and other adverse cardiovascular events. Additionally, several large studies have shown that treatment with statins prior to cardiac surgery and some non-cardiac surgeries can significantly reduce postoperative morbidity and mortality. There are, however, mixed conclusions and conflicting data regarding this benefit, with some studies showing a decrease in mortality and major cardiovascular events in the short-term and others failing to show benefit. Existing guidelines suggest using therapy to aggressively lower lipids in high-risk populations; however, statin use is only at about 40% in patients preparing to undergo cardiac surgery.

In previous studies that sought to elucidate the benefits of preoperative statins, a major limitation has been the retrospective nature of the study design. Controlling for confounding variables such as baseline patient characteristics and medication use is more difficult in retrospective studies. The published systematic reviews and analyses designed to bring clarity to the possible benefits of preoperative statins have also been limited, mainly by potential bias and insufficient power. To further investigate the effects of preoperative statin use, Liakopoulos and colleagues conducted a large meta-analysis involving over 30,000 patients undergoing cardiac surgery.

Meta-analysis design
The primary objectives of the meta-analysis were to determine if preoperative statins reduce early, all-cause mortality and decrease the incidence of major adverse post-operative events. Additionally, the authors sought to quantify the magnitude of the treatment effects. The secondary objective was to identify confounding factors that may limit the estimated treatment effects on the endpoints. The analysis included 19 unique studies published between 1999 and 2007; the total number of patients included was 31,725. Of these, 17,201 (54.2%) were given preoperative statin therapy and 14,524 (45.8%) were not.

The inclusion criteria allowed for randomized prospective clinical trials and observational studies published between 1966 and 2008 reporting the effects of preoperative statin therapy on postoperative outcomes in adult patients undergoing cardiac surgery. Trials included in this analysis met the following criteria: the use of a statin at any dose or duration prior to cardiac surgery, a comparison of patients who received preoperative statin therapy with those who did not, and data on clinical endpoints of early all-cause mortality, myocardial infarction, atrial fibrillation, stroke, and renal failure.

Of 1197 studies identified, 33 were reviewed and 19 met the inclusion criteria; 3 were randomized controlled trials (RCT), 3 had a prospective design, and 13 a retrospective design. All 19 used a study population of patients undergoing coronary artery bypass grafting (CABG), some with valve surgery and some without. The dose and duration of statins given varied among studies. All studies used in the analysis were examined for methodological quality, with an overall rating of good quality.

Meta-analysis findings
The clinical endpoints assessed are defined in Table 1. For the endpoint of early or short-term mortality, the overall incidence was 2.9%. This endpoint was included in 15 studies (28,517 patients), and 1 study that reported mortality after a 60-day follow-up. Between patients receiving preoperative statins and those not receiving preoperative statins, the absolute risk reduction with statin use was shown to be 1.5% (mortality rates of 2.2% vs. 3.7%, respectively, p<0.0001); or a reduction of 43% for short-term mortality (odds ratio [OR] 0.57, 95% CI: 0.49 to 0.67, p<0.0001).

For the endpoint of myocardial infarction, the overall incidence was 4.1%. This endpoint was included in 10 studies (14,330 patients). Between groups there was no significant reduction of myocardial infarction risk (4.2% vs. 3.9%, p=0.373; OR 1.11, 95% CI: 0.93 to 1.33, p=0.25).

For the endpoint of post-operation atrial fibrillation, the overall incidence was 26.9%. This endpoint was included in 7 studies (7,643 patients), and 3 studies reported new onset atrial fibrillation. Between the 2 groups of patients (statin vs. no statin treatment), the absolute risk reduction with statin use was 4.3% (24.2% vs. 29.2%, p<0.0001). These results gave an odds reduction of 33% for post-operative atrial fibrillation (OR 0.67, 95% CI: 0.51 to 0.88; p<0.0001).

For the endpoint of stroke, the overall incidence was 2.4%. This endpoint was included in 7 studies (16,390 patients). Between the 2 groups of patients, the absolute risk reduction was shown to be 0.8% (2.1% vs. 2.9% for statin vs. no statin use, p<0.001). These results gave an odds reduction of 26% for post-operative stroke (OR 0.74, 95% CI: 0.60 to 0.91; p<0.004).

Finally, for the endpoint of renal failure, the overall incidence was 4.1%. This endpoint was included in 5 studies (6,408 patients). Between groups there was no significant reduction of renal failure risk (3.9% vs. 4.5%, p=0.275; OR 0.78, 95% CI: 0.46 to 1.31, p=0.34).

Summary
According to the authors of the meta-analysis, this review demonstrates a substantial benefit to patients and a clear basis to advocate for an intensified pre-treatment statin regimen and rigorous post-op regimen per existing guidelines for patients undergoing cardiac surgery who have multiple cardiac risks and coronary heart disease. The authors further concluded that although the analysis included an appropriately large sample size, it would be premature to suggest that all patients undergoing cardiac surgery receive preoperative statins.

Reference
Laikopoulos O, Choi Y, Haldenwang PL, et al. Impact of preoperative statin therapy on adverse postoperative outcomes in patients undergoing cardiac surgery: a meta-analysis of over 30 000 patients. Eur Heart J. 2008;29(12):1548-1559.