Sustained postoperative anaemia is associated with an impaired outcome after coronary artery bypass graft surgery: insights from the IMAGINE trial.

OBJECTIVE: To investigate the association between sustained postoperative anaemia and outcome after coronary artery bypass graft (CABG) surgery. DESIGN: Retrospective analysis of the IMAGINE trial, which tested the effect of the ACE inhibitor quinapril on cardiovascular events after CABG. SETTING: Thoracic surgery clinic/outpatient department. PATIENTS: 2553 stable patients with left ventricular ejection fraction >40% 2-7 days after scheduled CABG. INTERVENTIONS: Randomisation to quinapril or placebo. MAIN OUTCOME MEASURES: Cox regression analysis for the association between postoperative anaemia and cardiovascular events and the effect of quinapril on the incidence of anaemia. RESULTS: Postoperative anaemia was sustained for >50 days in 44% of patients. Sustained postoperative anaemia was associated with an increased incidence of cardiovascular events during the first 3 months (adjusted HR (adjHR) 1.77, 95% CI 1.10 to 2.85, p=0.012) and during the maximum follow-up of 43 months (adjHR 1.37, 95% CI 1.14 to 1.65, p=0.008). When haemoglobin (Hb) was considered as a continuous variable, every 1 mg/dl decrease in Hb was associated with a 13% increase in cardiovascular events (adjHR 0.87, 95% CI 0.81 to 0.95, p=0.003) and a 22% increase in all-cause mortality (adjHR 0.78, 95% CI 0.60 to 0.99, p=0.034). Quinapril was associated with a slower postoperative recovery of Hb levels and a higher incidence of cardiovascular events in patients with anaemia (adjHR 1.60, 95% CI 1.1 to 2.4, p=0.024). CONCLUSIONS: Postoperative anaemia is common, frequently persists for months after CABG surgery and is associated with an impaired outcome. In patients with anaemia, ACE inhibitors slowed recovery from postoperative anaemia and increased the incidence of cardiovascular events after CABG.

Impact of previous percutaneous transluminal coronary angioplasty and/or stenting revascularization on outcomes after surgical revascularization: insights from the imagine study.

AIM: To determine the impact of previous coronary artery revascularization by percutaneous transluminal coronary angioplasty and/or stenting (PCI) on outcome after subsequent coronary artery bypass grafting (CABG). METHODS AND RESULTS: The ischaemia management with Accupril post-bypass Graft via Inhibition of the coNverting Enzyme (IMAGINE) trial, conducted between November 1999 and September 2004, tested whether early initiation of an angiotensin-converting enzyme inhibitor post-CABG, in stable patients with LVEF >or=40%, would reduce cardiovascular events. Of the 2489 patients included in the IMAGINE trial, undergoing their first operation, 430 had a history of PCI prior to surgery (PCI group), and 2059 were referred to surgery without previous PCI (non-PCI group). There was a significant increase in the primary IMAGINE endpoint in the PCI group, HR = 1.53 [1.17-1.98], P = 0.0016. Coronary revascularization, HR = 1.80 [1.13-2.87], P = 0.014, unstable angina requiring hospitalization, HR = 2.43 [1.52-3.89], P = 0.0002, were the two individual components that significantly increased in the PCI group, even when adjusted for baseline characteristics (age, sex, history of myocardial infarction or stroke, diabetes, treatment group, or off-pump surgery). CONCLUSION: Patients with left ventricular ejection fraction >or=40% having a history of PCI prior to surgery had a worse outcome post-CABG than those with no prior PCI. Further studies are needed to investigate whether these results apply for drug eluting stents.

Effects of angiotensin-converting enzyme inhibition in low-risk patients early after coronary artery bypass surgery.

BACKGROUND: Early after coronary artery bypass surgery (CABG), activation of numerous neurohumoral and endogenous vasodilator systems occurs that could be influenced favorably by angiotensin-converting enzyme inhibitors. METHODS AND RESULTS: The Ischemia Management with Accupril post-bypass Graft via Inhibition of the coNverting Enzyme (IMAGINE) trial tested whether early initiation (< or = 7 days) of an angiotensin-converting enzyme inhibitor after CABG reduced cardiovascular events in stable patients with left ventricular ejection fraction > or = 40%. The trial was a double-blind, placebo-controlled study of 2553 patients randomly assigned to quinapril, target dose 40 mg/d, or placebo, who were followed up to a maximum of 43 months. The mean (SD) age was 61 (10) years. The incidence of the primary composite end point (cardiovascular death, resuscitated cardiac arrest, nonfatal myocardial infarction, coronary revascularization, unstable angina or heart failure requiring hospitalization, documented angina, and stroke) was 13.7% in the quinapril group and 12.2% in the placebo group (hazard ratio 1.15, 95% confidence interval 0.92 to 1.42, P=0.212) over a median follow-up of 2.95 years. The incidence of the primary composite end point increased significantly in the first 3 months after CABG in the quinapril group (hazard ratio 1.52, 95% confidence interval 1.03 to 2.26, P=0.0356). Adverse events also increased in the quinapril group, particularly during the first 3 months after CABG. CONCLUSIONS: In patients at low risk of cardiovascular events after CABG, routine early initiation of angiotensin-converting enzyme inhibitor therapy does not appear to improve clinical outcome up to 3 years after CABG; however, it increases the incidence of adverse events, particularly early after CABG. Thus, early after CABG, initiation of angiotensin-converting enzyme inhibitor therapy should be individualized and continually reassessed over time according to risk.

Long-term trandolapril treatment is associated with reduced aortic stiffness: the prevention of events with angiotensin-converting enzyme inhibition hemodynamic substudy.

The Prevention of Events with Angiotensin Converting Enzyme inhibition (PEACE) trial evaluated angiotensin-converting enzyme inhibition with trandolapril versus placebo added to conventional therapy in patients with stable coronary disease and preserved left ventricular function. The PEACE hemodynamic substudy evaluated effects of trandolapril on pulsatile hemodynamics. Hemodynamic studies were performed in 300 participants from 5 PEACE centers a median of 52 months (range, 25 to 80 months) after random assignment to trandolapril at a target dose of 4 mg per day or placebo. Central pulsatile hemodynamics and carotid-femoral pulse wave velocity were assessed by using echocardiography, tonometry of the carotid and femoral arteries, and body surface transit distances. Patients randomly assigned to trandolapril tended to be older (mean+/-SD: 64.2+/-7.9 versus 62.9+/-7.7 years; P=0.14), with a higher body mass index (28.5+/-4.0 versus 27.8+/-3.9 kg/m(2); P=0.09) and lower ejection fraction (57.1+/-8.1% versus 58.7+/-8.4%; P<0.01). At the time of the hemodynamic substudy, the trandolapril group had lower mean arterial pressure (93.1+/-10.2 versus 96.3+/-11.3 mm Hg; P<0.01) and lower carotid-femoral pulse wave velocity (geometric mean [95% CI]: 10.4 m/s [10.0 to 10.9 m/s] versus 11.2 m/s [10.7 to 11.8 m/s]; P=0.02). The difference in carotid-femoral pulse wave velocity persisted (P<0.01) in an analysis that adjusted for baseline characteristics and follow-up mean pressure. In contrast, there was no difference in aortic compliance, characteristic impedance, augmentation index, or total arterial compliance. Angiotensin-converting enzyme inhibition with trandolapril produced a modest reduction in carotid-femoral pulse wave velocity, a measure of aortic wall stiffness, beyond what would be expected from blood pressure lowering or differences in baseline characteristics alone.

Predictors of intracranial hemorrhage with fibrinolytic therapy in unselected community patients: a report from the FASTRAK II project.

BACKGROUND: Patients at high risk for intracranial hemorrhage (ICH) are generally excluded from thrombolytic trials. Because the frequency and predictors of ICH reported from these studies may not be widely applicable, we sought to examine this matter further in unselected patients with acute myocardial infarction in the community. METHODS: FASTRAK II is a prospective ongoing registry of acute coronary syndromes involving 111 Canadian hospitals. Trained medical personnel recorded admission, treatment, and discharge data on patients admitted with acute coronary syndromes. RESULTS: From January 1, 1998, to December 31, 2000, 12,739 patients received fibrinolytic therapy for acute myocardial infarction. Of these, 146 patients (1.15%) sustained strokes and 82 patients (0.65%) had an ICH. Advanced age, female sex, history of cerebrovascular event, and systolic hypertension on arrival (systolic blood pressure >160 mm Hg) were identified with a multivariate logistic regression model to be important independent risks factors for ICH. Patients receiving streptokinase had a lower risk of ICH. Among the patients at high risk for ICH, the ICH rates remained low, ranging from 0.7% to 1.8%. CONCLUSION: ICH is an infrequent event after fibrinolytic therapy in ST-elevation MI; this low rate supports broad penetration of this therapy. Simple clinical characteristics are useful in predicting the risk of ICH and allow a clinician to individualize the risk-benefit assessment of this therapy.

CCORT/CCS quality indicators for acute myocardial infarction care.

BACKGROUND: Although quality indicators for the care of acute myocardial infarction (AMI) patients have been described for other countries, there are none specifically designed for the Canadian health care system. The authors' goal was to develop a set of Canadian quality indicators for AMI care. METHODS: A literature review identified existing quality indicators for AMI care. A list of potential indicators was assessed by a nine-member panel of clinicians from a variety of disciplines using a modified-Delphi panel process. After an initial round of rating the potential indicators, a series of indicators was identified for a second round of discussion at a national meeting. Further refinement of indicators occurred following a teleconference and review by external reviewers. RESULTS: To identify an AMI cohort, case definition criteria were developed, using a hospital discharge diagnosis for AMI of International Classification of Diseases-Ninth revision (ICD-9) code 410.x. Thirty-seven indicators for AMI care were established. Pharmacological process of care indicators included administration of acetylsalicylic acid, beta-blockers, angiotensin-converting enzyme inhibitors, thrombolytics and statins. Mortality and readmissions for AMI, unstable angina and congestive heart failure were recommended as outcome indicators. Nonpharmacological indicators included median length of stay in the emergency department, and median waiting times for cardiac catheterization, percutaneous coronary intervention and/or coronary artery bypass graft surgery. INTERPRETATION: A set of Canadian quality indicators for the care of AMI patients has been established. It is anticipated that these indicators will be useful to clinicians and researchers who want to measure and improve the quality of AMI patient care in Canada.