Bisoprolol and Fluvastatin for the Reduction of Perioperative Cardiac Mortality and Myocardial Infarction in Intermediate-Risk Patients Undergoing Noncardiovascular Surgery: A Randomized Controlled Trial (DECREASE-IV)

Abstract

In Brief Objective: This study evaluated the effectiveness and safety of beta-blockers and statins for the prevention of perioperative cardiovascular events in intermediate-risk patients undergoing noncardiovascular surgery. Summary Background Data: Beta-blockers and statins reduce perioperative cardiac events in high-risk patients undergoing vascular surgery by restoring the myocardial oxygen supply/demand balance and/or stabilizing coronary plaques. However, their effects in intermediate-risk patients remained ill-defined. Methods: In this randomized open-label 2 × 2 factorial design trial 1066 intermediate cardiac risk patients were assigned to bisoprolol, fluvastatin, combination treatment, or control therapy before surgery (median: 34 days). Intermediate risk was defined by an estimated risk of perioperative cardiac death and myocardial infarction (MI) of 1% to 6%, using clinical data and type of surgery. Starting dose of bisoprolol was 2.5 mg daily, titrated to a perioperative heart rate of 50 to 70 beats per minute. Fluvastatin was prescribed in a fixed dose of 80 mg. The primary end point was the composite of 30-day cardiac death and MI. This study is registered in the ISRCTN registry and has the ID number ISRCTN47637497. Results: Patients randomized to bisoprolol (N = 533) had a lower incidence of perioperative cardiac death and nonfatal MI than those randomized to bisoprolol-control (2.1% vs. 6.0% events; hazard ratios: 0.34; 95% confidence intervals: 0.17–0.67; P = 0.002). Patients randomized to fluvastatin experienced a lower incidence of the end point than those randomized to fluvastatin-control therapy (3.2% vs. 4.9% events; hazard ratios: 0.65; 95% confidence intervals: 0.35–1.10), but statistical significance was not reached (P = 0.17). Conclusion: Bisoprolol was associated with a significant reduction of 30-day cardiac death and nonfatal MI, while fluvastatin showed a trend for improved outcome. In this randomized trial including 1066 patients beta-blocker therapy was associated with a significant reduction (hazard ratios: 0.34, 95% confidence intervals: 0.17–0.67) in perioperative cardiovascular events in intermediate-risk patients undergoing noncardiovascular surgery. However, statin therapy was not associated with a significant reduction in perioperative cardiovascular events (hazard ratios: 0.65; 95% confidence intervals: 0.35–1.10).