Impact of Preoperative Statin Therapy on Adverse Postoperative Outcomes
Impact of Preoperative Statin Therapy on Adverse Postoperative Outcomes
Aims: To determine the strength of evidence for preoperative statin use for prevention of adverse postoperative outcomes in patients undergoing cardiac surgery.
Methods and Results: After literature search in major databases, 19 studies were identified [three RCT (randomized prospective clinical trials), 16 observational] that reported outcomes of 31725 cardiac surgery patients with (n=17201; 54%) or without (n=14524; 46%) preoperative statin therapy. Outcomes that were analysed included early all-cause mortality (30-day mortality), myocardial infarction (MI), atrial fibrillation (AF), stroke and renal failure. Odds ratio (OR) with 95% confidence intervals (95%CI) were reported using fixed or random effect models and publication bias was assessed. Preoperative statin therapy resulted in a 1.5% absolute risk reduction (2.2 vs. 3.7%; P<0.0001) and 43% odds reduction for early all-cause mortality (OR 0.57; 95%CI: 0.49–0.67). A significant reduction (P < 0.01) in statin pretreated patients was also observed for AF (24.9 vs. 29.3%; OR 0.67, 95%CI: 0.51–0.88), stroke (2.1 vs. 2.9%, OR 0.74, 95%CI: 0.60–0.91), but not for MI (OR 1.11; 95%CI: 0.93–1.33) or renal failure (OR 0.78, 95%CI: 0.46–1.31). Funnel plot and Egger's regression analysis (P=0.60) excluded relevant publication bias.
Conclusion: Our meta-analysis provides evidence that preoperative statin therapy exerts substantial clinical benefit on early postoperative adverse outcomes in cardiac surgery patients, but underscores the need for RCT trials.
Long-term lipid-lowering therapy with inhibitors of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (statins) prevents progression of atherosclerotic coronary artery and vein graft disease, reduces the need for repeat revascularization and ultimately decreases adverse cardiovascular events and mortality in patients after coronary artery bypass grafting (CABG). Beyond their lipid-lowering actions, statins are known to exert multiple pleiotropic effects including improved endothelial function, plaque stabilization, decrease of inflammatory markers and attenuation of myocardial ischaemia-reperfusion injury that can offer direct organ protection and contribute to improved clinical outcome in the early postoperative course. Accumulating evidence from recent trials also suggests that statin use in patients undergoing non-cardiac surgery improves the early postoperative outcome by reducing adverse cardiovascular events and all-cause mortality.
However in patients undergoing cardiac surgery results are conflicting with several studies reporting a decrease in short-term mortality and major cardiovascular events including myocardial infarction (MI), atrial fibrillation (AF), stroke, and renal failure in patients receiving preoperative statins, while others have failed to show a beneficial effect of statins on these endpoints. These discrepancies arise primarily from the predominantly retrospective design of these studies, with inability to control for confounding factors such as preoperative patient risk factors and medications. Attempts to elucidate the potential benefits of a preoperative statin therapy in cardiac surgery were made by previous reviews that unfortunately lacked from sufficient power and suffered from potential publication bias, making interpretation of the presented data difficult. Thus, statin utilization in patients with CAD (coronary artery disease) admitted for cardiac surgery remains suboptimal (~40%), despite existing guidelines of the ACC/AHA, NCEP, and ATPIII to aggressively lower lipids in this high-risk patient population, and underscores the need for providing further robust evidence in order to change current clinical practice.
In view of the limited clarity of available data, we conducted a systematic review and meta-analysis to assess the strength of evidence supporting the use of statins before cardiac surgery with the primary objective to determine if statins reduce early, all-cause mortality and decrease the incidence of major adverse postoperative events. Additionally, we desired to quantify the magnitude of treatment effects. The secondary objective was to identify confounding factors that may limit the estimated treatment effects on the measured endpoints.
Abstract and Introduction
Abstract
Aims: To determine the strength of evidence for preoperative statin use for prevention of adverse postoperative outcomes in patients undergoing cardiac surgery.
Methods and Results: After literature search in major databases, 19 studies were identified [three RCT (randomized prospective clinical trials), 16 observational] that reported outcomes of 31725 cardiac surgery patients with (n=17201; 54%) or without (n=14524; 46%) preoperative statin therapy. Outcomes that were analysed included early all-cause mortality (30-day mortality), myocardial infarction (MI), atrial fibrillation (AF), stroke and renal failure. Odds ratio (OR) with 95% confidence intervals (95%CI) were reported using fixed or random effect models and publication bias was assessed. Preoperative statin therapy resulted in a 1.5% absolute risk reduction (2.2 vs. 3.7%; P<0.0001) and 43% odds reduction for early all-cause mortality (OR 0.57; 95%CI: 0.49–0.67). A significant reduction (P < 0.01) in statin pretreated patients was also observed for AF (24.9 vs. 29.3%; OR 0.67, 95%CI: 0.51–0.88), stroke (2.1 vs. 2.9%, OR 0.74, 95%CI: 0.60–0.91), but not for MI (OR 1.11; 95%CI: 0.93–1.33) or renal failure (OR 0.78, 95%CI: 0.46–1.31). Funnel plot and Egger's regression analysis (P=0.60) excluded relevant publication bias.
Conclusion: Our meta-analysis provides evidence that preoperative statin therapy exerts substantial clinical benefit on early postoperative adverse outcomes in cardiac surgery patients, but underscores the need for RCT trials.
Introduction
Long-term lipid-lowering therapy with inhibitors of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (statins) prevents progression of atherosclerotic coronary artery and vein graft disease, reduces the need for repeat revascularization and ultimately decreases adverse cardiovascular events and mortality in patients after coronary artery bypass grafting (CABG). Beyond their lipid-lowering actions, statins are known to exert multiple pleiotropic effects including improved endothelial function, plaque stabilization, decrease of inflammatory markers and attenuation of myocardial ischaemia-reperfusion injury that can offer direct organ protection and contribute to improved clinical outcome in the early postoperative course. Accumulating evidence from recent trials also suggests that statin use in patients undergoing non-cardiac surgery improves the early postoperative outcome by reducing adverse cardiovascular events and all-cause mortality.
However in patients undergoing cardiac surgery results are conflicting with several studies reporting a decrease in short-term mortality and major cardiovascular events including myocardial infarction (MI), atrial fibrillation (AF), stroke, and renal failure in patients receiving preoperative statins, while others have failed to show a beneficial effect of statins on these endpoints. These discrepancies arise primarily from the predominantly retrospective design of these studies, with inability to control for confounding factors such as preoperative patient risk factors and medications. Attempts to elucidate the potential benefits of a preoperative statin therapy in cardiac surgery were made by previous reviews that unfortunately lacked from sufficient power and suffered from potential publication bias, making interpretation of the presented data difficult. Thus, statin utilization in patients with CAD (coronary artery disease) admitted for cardiac surgery remains suboptimal (~40%), despite existing guidelines of the ACC/AHA, NCEP, and ATPIII to aggressively lower lipids in this high-risk patient population, and underscores the need for providing further robust evidence in order to change current clinical practice.
In view of the limited clarity of available data, we conducted a systematic review and meta-analysis to assess the strength of evidence supporting the use of statins before cardiac surgery with the primary objective to determine if statins reduce early, all-cause mortality and decrease the incidence of major adverse postoperative events. Additionally, we desired to quantify the magnitude of treatment effects. The secondary objective was to identify confounding factors that may limit the estimated treatment effects on the measured endpoints.
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