Aprotinin plus ACE inhibitors during off-pump surgery linked to renal dysfunction
By Sara Carrillo de Albornoz
08 February 2008
The Lancet 2008; 371: 475-482
MedWire News: Patients undergoing off-pump cardiac surgery who are treated with aprotinin and preoperative angiotensin-converting enzyme (ACE) inhibitors are at high risk for postoperative renal dysfunction, UK researchers report in The Lancet.
"We recommend that it might be beneficial for patients to discontinue any use of an ACE inhibitor before undergoing elective off-pump cardiac surgery, particularly patients with a history of renal impairment," say Kai Zacharowski and colleagues from the Bristol Royal Infirmary.
Aprotinin is an antifibrinolytic serine protease inhibitor that reduces peri-operative bleeding and decreases the need for blood transfusion and re-operation in patients undergoing cardiac surgery, but concerns have been raised about its role in renal impairment, the authors comment.
Zacharowski and team examined the association between aprotinin and renal dysfunction in 9012 patients undergoing cardiac surgery, of whom 5434 were operated on-pump and 3672 off-pump.
They separately analyzed the incidence of renal dysfunction in patients treated with aprotinin, tranexamic acid, or no antifibrinolytic therapy in combination with or without pre-operative ACE inhibitors.
After propensity adjustment, only patients undergoing off-pump surgery and treated with both ACE inhibitors and aprotinin were at high risk for postoperative renal dysfunction (odds ratio=2.87, p=0.013).
Among patients undergoing on-pump surgery, aprotinin - with or without ACE inhibitors - did not significantly increase the risk for renal dysfunction.
Zacharowski and co-workers conclude: "Our results have shown that aprotinin seems to be safe during on-pump cardiac surgery.
"However, the combination of aprotinin and ACE inhibitors during off -pump cardiac surgery is associated with a significant risk of postoperative renal dysfunction."
They add: "The international communities of cardiac anesthesia and surgery face controversy regarding the use of aprotinin."
Journal
Showing posts with label Angiotensin-Converting Enzyme Inhibito. Show all posts
Showing posts with label Angiotensin-Converting Enzyme Inhibito. Show all posts
Friday, February 8, 2008
Monday, January 28, 2008
ACE inhibitor prevents cardiac rupture after acute MI
Causes of death in patients with acute myocardial infarction treated with angiotensin-converting enzyme inhibitors: Findings from the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto (GISSI)–3 trial
American Heart Journal
Volume 155, Issue 2, Pages 388-394 (February 2008)
Giovanni Pedrazzini, MD, Eugenio Santoro, MS, Roberto Latini, MD, Laurie Fromm, PharmD, Maria Grazia Franzosi, BiolScD, Tiziano Mocetti, MD, Lidia Staszewsky, MD, Simona Barlera, MS, Gianni Tognoni, MD, Aldo P. Maggioni, MD
Background
The causes of death occurring in clinical trials of myocardial infarction (MI) are scarcely reported in the literature. The present analysis is aimed to describe the inhospital causes of death in patients with acute MI stratified to angiotensin converting enzyme (ACE) inhibitor treatment/no treatment, as described in the GISSI-3 trial. Furthermore, the 5-year survival analysis of GISSI-3 patients is reported.
Methods and Results
An independent committee assigned the definition of causes of death of GISSI-3 based on clinical and/or anatomical data. Univariate and multivariable analyses were performed to identify the predictors of early and late deaths. Kaplan-Meier mortality curves were used to describe the effects of ACE-I treatment on mortality on a median follow-up period of 56 months.
Patients receiving lisinopril had fewer inhospital cardiac deaths than patients allocated to the no-lisinopril group (4.7% vs 5.3%, P = .052), corresponding to a 12% relative risk reduction. The risk of dying from cardiac rupture was reduced by 39% by lisinopril treatment. The improvement in survival associated with the lisinopril treatment was mainly due to a reduction in cardiac rupture, electromechanical dissociation, and pump failure occurring early (within 4 days) from the onset of MI symptoms.
The beneficial effects of lisinopril observed at 6 weeks (8 fewer deaths per 1000 treated patients) were maintained up to nearly 5 years (10 fewer deaths per 1000).
Conclusions
Early administration of ACE inhibitors in unselected patients with acute MI should be considered standard therapy to reduce early deaths, specifically those due to cardiac rupture. The early beneficial effect persisted up to nearly 5 years.
American Heart Journal
Volume 155, Issue 2, Pages 388-394 (February 2008)
Giovanni Pedrazzini, MD, Eugenio Santoro, MS, Roberto Latini, MD, Laurie Fromm, PharmD, Maria Grazia Franzosi, BiolScD, Tiziano Mocetti, MD, Lidia Staszewsky, MD, Simona Barlera, MS, Gianni Tognoni, MD, Aldo P. Maggioni, MD
Background
The causes of death occurring in clinical trials of myocardial infarction (MI) are scarcely reported in the literature. The present analysis is aimed to describe the inhospital causes of death in patients with acute MI stratified to angiotensin converting enzyme (ACE) inhibitor treatment/no treatment, as described in the GISSI-3 trial. Furthermore, the 5-year survival analysis of GISSI-3 patients is reported.
Methods and Results
An independent committee assigned the definition of causes of death of GISSI-3 based on clinical and/or anatomical data. Univariate and multivariable analyses were performed to identify the predictors of early and late deaths. Kaplan-Meier mortality curves were used to describe the effects of ACE-I treatment on mortality on a median follow-up period of 56 months.
Patients receiving lisinopril had fewer inhospital cardiac deaths than patients allocated to the no-lisinopril group (4.7% vs 5.3%, P = .052), corresponding to a 12% relative risk reduction. The risk of dying from cardiac rupture was reduced by 39% by lisinopril treatment. The improvement in survival associated with the lisinopril treatment was mainly due to a reduction in cardiac rupture, electromechanical dissociation, and pump failure occurring early (within 4 days) from the onset of MI symptoms.
The beneficial effects of lisinopril observed at 6 weeks (8 fewer deaths per 1000 treated patients) were maintained up to nearly 5 years (10 fewer deaths per 1000).
Conclusions
Early administration of ACE inhibitors in unselected patients with acute MI should be considered standard therapy to reduce early deaths, specifically those due to cardiac rupture. The early beneficial effect persisted up to nearly 5 years.
Tuesday, October 9, 2007
Adverse Effects of Combination Angiotensin II Receptor Blockers Plus Angiotensin-Converting Enzyme Inhibitors for Left Ventricular Dysfunction
Adverse Effects of Combination Angiotensin II Receptor Blockers Plus Angiotensin-Converting Enzyme Inhibitors for Left Ventricular Dysfunction
A Quantitative Review of Data From Randomized Clinical Trials
Christopher O. Phillips, MD, MPH; Amir Kashani, MS, MD; Dennis K. Ko, MD; Gary Francis, MD; Harlan M. Krumholz, MD, SM
Arch Intern Med. 2007;167:1930-1936. (October 8, 2007)
Background We performed a meta-analysis of randomized controlled trials to assess ongoing concerns about the safety profile of combination angiotensin II receptor blockers (ARBs) plus angiotensin-converting enzyme (ACE) inhibitors in symptomatic left ventricular dysfunction.
Methods MEDLINE (January 1966–December 2006) and Web sites for the National Institute of Health Clinical Trials and the Food and Drug Administration were searched for eligible RCTs that included 500 or more subjects, had a follow-up of 3 months or longer, and reported adverse effects. We used a random effects model to calculate the relative risk (RR) and 95% confidence interval (CI) for the following outcome measures: medication discontinuations because of adverse effects, worsening renal function (an increase in serum creatinine level of > 0.5 mg/dL [to convert to micromoles per liter, multiply by 88.4]), hyperkalemia (serum potassium level > 5.5 mEq/L [to convert to millimoles per liter, multiply by 1]), and symptomatic hypotension.
Results Four studies (N = 17 337; mean follow-up, 25 months [range, 11-41 months]) were selected. Combination ARB plus ACE inhibitor vs control treatment that included ACE inhibitors was associated with significant increases in medication discontinuations because of adverse effects in patients with chronic heart failure (RR, 1.38 [95% CI, 1.22-1.55]) or in patients with acute myocardial infarction with symptomatic left ventricular dysfunction (RR, 1.17 [95% CI, 1.03-1.34]), and for both conditions there were significant increases in worsening renal function (RR, 2.17 [95% CI, 1.59-2.97] and RR, 1.61 [95% CI, 1.31-1.98], respectively), hyperkalemia (RR, 4.87 [95% CI, 2.39-9.94] and RR, 1.33 [95% CI, 0.90-1.98], respectively; the latter was not significant), and symptomatic hypotension (RR, 1.50 [95% CI, 1.09-2.07], and RR, 1.48 [95% CI, 1.33-3.18], respectively).
Conclusion Combination ARB plus ACE inhibitor therapy in subjects with symptomatic left ventricular dysfunction was accompanied by marked increases in adverse effects.
A Quantitative Review of Data From Randomized Clinical Trials
Christopher O. Phillips, MD, MPH; Amir Kashani, MS, MD; Dennis K. Ko, MD; Gary Francis, MD; Harlan M. Krumholz, MD, SM
Arch Intern Med. 2007;167:1930-1936. (October 8, 2007)
Background We performed a meta-analysis of randomized controlled trials to assess ongoing concerns about the safety profile of combination angiotensin II receptor blockers (ARBs) plus angiotensin-converting enzyme (ACE) inhibitors in symptomatic left ventricular dysfunction.
Methods MEDLINE (January 1966–December 2006) and Web sites for the National Institute of Health Clinical Trials and the Food and Drug Administration were searched for eligible RCTs that included 500 or more subjects, had a follow-up of 3 months or longer, and reported adverse effects. We used a random effects model to calculate the relative risk (RR) and 95% confidence interval (CI) for the following outcome measures: medication discontinuations because of adverse effects, worsening renal function (an increase in serum creatinine level of > 0.5 mg/dL [to convert to micromoles per liter, multiply by 88.4]), hyperkalemia (serum potassium level > 5.5 mEq/L [to convert to millimoles per liter, multiply by 1]), and symptomatic hypotension.
Results Four studies (N = 17 337; mean follow-up, 25 months [range, 11-41 months]) were selected. Combination ARB plus ACE inhibitor vs control treatment that included ACE inhibitors was associated with significant increases in medication discontinuations because of adverse effects in patients with chronic heart failure (RR, 1.38 [95% CI, 1.22-1.55]) or in patients with acute myocardial infarction with symptomatic left ventricular dysfunction (RR, 1.17 [95% CI, 1.03-1.34]), and for both conditions there were significant increases in worsening renal function (RR, 2.17 [95% CI, 1.59-2.97] and RR, 1.61 [95% CI, 1.31-1.98], respectively), hyperkalemia (RR, 4.87 [95% CI, 2.39-9.94] and RR, 1.33 [95% CI, 0.90-1.98], respectively; the latter was not significant), and symptomatic hypotension (RR, 1.50 [95% CI, 1.09-2.07], and RR, 1.48 [95% CI, 1.33-3.18], respectively).
Conclusion Combination ARB plus ACE inhibitor therapy in subjects with symptomatic left ventricular dysfunction was accompanied by marked increases in adverse effects.
Subscribe to:
Posts (Atom)