Effects of ACEI Therapy on Clinical Outcome in Patients Undergoing CABG
Effects of ACEI Therapy on Clinical Outcome in Patients Undergoing CABG
Objectives: This study evaluates the effect of pre-operative angiotensin-converting enzyme inhibitor (ACEI) therapy on early clinical outcomes after coronary artery bypass grafting (CABG).
Background: Therapy with ACEIs has been shown to reduce the rate of mortality and prevent cardiovascular events in patients with coronary artery disease. However, their pre-operative use in patients undergoing CABG is still controversial.
Methods: A retrospective, observational, cohort study was undertaken of prospectively collected data on 10,023 consecutive patients undergoing isolated CABG between April 1996 and May 2008. Of these, 3,052 patients receiving pre-operative ACEI were matched to a control group by propensity score analysis.
Results: Overall rate of mortality was 1%. Pre-operative ACEI therapy was associated with a doubling in the risk of death (1.3% vs. 0.7%; odds ratio [OR]: 2.00, 95% confidence interval [CI]: 1.17 to 3.42; p = 0.013). There was also a significant difference between the ACEI and control group in the risk of post-operative renal dysfunction (PRD) (7.1% vs. 5.4%; OR: 1.36, 95% CI: 1.1 to 1.67; p = 0.006), atrial fibrillation (AF) (25% vs. 20%; OR: 1.34, 95% CI: 1.18 to 1.51; p < 0.0001), and increased use of inotropic support (45.9% vs. 41.1%; OR: 1.22, 95% CI: 1.1 to 1.36; p < 0.0001). In a multivariate analysis, pre-operative ACEI treatment was an independent predictor of mortality (p = 0.04), PRD (p = 0.0002), use of inotropic drugs (p < 0.0001), and AF (p < 0.0001).
Conclusions: Pre-operative therapy with ACEI is associated with an increased risk of mortality, use of inotropic support, PRD, and new onset of post-operative AF.
Angiotensin-converting enzyme inhibitors (ACEIs) have been shown to reduce the rate of mortality and to prevent cardiovascular events in patients with coronary artery disease, especially after acute myocardial infarction (MI). The authors of the EUROPA (European Trial on Reduction of Cardiac Events With Perindopril in Stable Coronary Artery Disease) study showed a 14% reduction in total rate of mortality, nonfatal MI, unstable angina, and cardiac arrest. Moreover, in a meta-analysis of 4 trials that included 98,496 patients with early MI, treatment with ACEI was associated with an average 7% proportional reduction in mortality within 30 days. ACEIs, through the reduction of angiotensin II and increased bradykinin availability, explicate their cardioprotective proprieties on left ventricular afterload and remodeling, improving cardiac hemodynamics, and reducing ventricular mass.
In addition to lowering blood pressure, ACEIs possess a vasculoprotective and anti-ischemic action through their antiatherosclerotic, antithrombotic, anti-inflammatory effects. Consequently, most patients with coronary artery disease receive these drugs. Nevertheless, there are still significant controversies regarding the pre-operative use of ACEIs in patients undergoing coronary artery bypass grafting (CABG). It has been hypothesized by several authors that the pre-operative administration of ACEI in these patients contributes to lowering of systemic vascular resistance and vasoplegia in the early post-operative phase, resulting in hypotension and renal dysfunction.
Authors of the IMAGINE (Ischemia Management With Accupril Post Bypass Graft via Inhibition of Angiotensin Converting Enzyme) study reported that, in CABG patients at low risk of cardiovascular events, routine early initiation of ACEI therapy does not improve clinical outcome up to 3 years after surgery and may increase adverse events during the first 3 months. Others authors concluded that pre-operative treatment with ACEIs does not cause hypotension and can safely be used in patients undergoing cardiac surgery. A national survey in the United Kingdom revealed that the majority of cardiac surgeons believe that the use of pre-operative ACEIs increases use of fluids, inotropes, and vasoconstrictors. However, only 39% of respondents practiced discontinuing the drug before operation. The aim of the present study was, therefore to review our institutional database to evaluate the effects of pre-operative ACEI treatment on early clinical outcomes after CABG.
Abstract and Introduction
Abstract
Objectives: This study evaluates the effect of pre-operative angiotensin-converting enzyme inhibitor (ACEI) therapy on early clinical outcomes after coronary artery bypass grafting (CABG).
Background: Therapy with ACEIs has been shown to reduce the rate of mortality and prevent cardiovascular events in patients with coronary artery disease. However, their pre-operative use in patients undergoing CABG is still controversial.
Methods: A retrospective, observational, cohort study was undertaken of prospectively collected data on 10,023 consecutive patients undergoing isolated CABG between April 1996 and May 2008. Of these, 3,052 patients receiving pre-operative ACEI were matched to a control group by propensity score analysis.
Results: Overall rate of mortality was 1%. Pre-operative ACEI therapy was associated with a doubling in the risk of death (1.3% vs. 0.7%; odds ratio [OR]: 2.00, 95% confidence interval [CI]: 1.17 to 3.42; p = 0.013). There was also a significant difference between the ACEI and control group in the risk of post-operative renal dysfunction (PRD) (7.1% vs. 5.4%; OR: 1.36, 95% CI: 1.1 to 1.67; p = 0.006), atrial fibrillation (AF) (25% vs. 20%; OR: 1.34, 95% CI: 1.18 to 1.51; p < 0.0001), and increased use of inotropic support (45.9% vs. 41.1%; OR: 1.22, 95% CI: 1.1 to 1.36; p < 0.0001). In a multivariate analysis, pre-operative ACEI treatment was an independent predictor of mortality (p = 0.04), PRD (p = 0.0002), use of inotropic drugs (p < 0.0001), and AF (p < 0.0001).
Conclusions: Pre-operative therapy with ACEI is associated with an increased risk of mortality, use of inotropic support, PRD, and new onset of post-operative AF.
Introduction
Angiotensin-converting enzyme inhibitors (ACEIs) have been shown to reduce the rate of mortality and to prevent cardiovascular events in patients with coronary artery disease, especially after acute myocardial infarction (MI). The authors of the EUROPA (European Trial on Reduction of Cardiac Events With Perindopril in Stable Coronary Artery Disease) study showed a 14% reduction in total rate of mortality, nonfatal MI, unstable angina, and cardiac arrest. Moreover, in a meta-analysis of 4 trials that included 98,496 patients with early MI, treatment with ACEI was associated with an average 7% proportional reduction in mortality within 30 days. ACEIs, through the reduction of angiotensin II and increased bradykinin availability, explicate their cardioprotective proprieties on left ventricular afterload and remodeling, improving cardiac hemodynamics, and reducing ventricular mass.
In addition to lowering blood pressure, ACEIs possess a vasculoprotective and anti-ischemic action through their antiatherosclerotic, antithrombotic, anti-inflammatory effects. Consequently, most patients with coronary artery disease receive these drugs. Nevertheless, there are still significant controversies regarding the pre-operative use of ACEIs in patients undergoing coronary artery bypass grafting (CABG). It has been hypothesized by several authors that the pre-operative administration of ACEI in these patients contributes to lowering of systemic vascular resistance and vasoplegia in the early post-operative phase, resulting in hypotension and renal dysfunction.
Authors of the IMAGINE (Ischemia Management With Accupril Post Bypass Graft via Inhibition of Angiotensin Converting Enzyme) study reported that, in CABG patients at low risk of cardiovascular events, routine early initiation of ACEI therapy does not improve clinical outcome up to 3 years after surgery and may increase adverse events during the first 3 months. Others authors concluded that pre-operative treatment with ACEIs does not cause hypotension and can safely be used in patients undergoing cardiac surgery. A national survey in the United Kingdom revealed that the majority of cardiac surgeons believe that the use of pre-operative ACEIs increases use of fluids, inotropes, and vasoconstrictors. However, only 39% of respondents practiced discontinuing the drug before operation. The aim of the present study was, therefore to review our institutional database to evaluate the effects of pre-operative ACEI treatment on early clinical outcomes after CABG.
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