Michelle M. Graham

Aspirin in patients undergoing noncardiac surgery

BACKGROUND There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery, both among patients who are already on an aspirin regimen and among those who are not. METHODS Using a 2-by-2 factorial trial design, we randomly assigned 10,010 patients who were preparing to undergo noncardiac surgery and were at risk for vascular complications to receive aspirin or placebo and clonidine or placebo. The results of the aspirin trial are reported here. The patients were stratified according to whether they had not been taking aspirin before the study (initiation stratum, with 5628 patients) or they were already on an aspirin regimen (continuation stratum, with 4382 patients). Patients started taking aspirin (at a dose of 200 mg) or placebo just before surgery and continued it daily (at a dose of 100 mg) for 30 days in the initiation stratum and for 7 days in the continuation stratum, after which patients resumed their regular aspirin regimen. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days. RESULTS The primary outcome occurred in 351 of 4998 patients (7.0%) in the aspirin group and in 355 of 5012 patients (7.1%) in the placebo group (hazard ratio in the aspirin group, 0.99; 95% confidence interval [CI], 0.86 to 1.15; P=0.92). Major bleeding was more common in the aspirin group than in the placebo group (230 patients [4.6%] vs. 188 patients [3.8%]; hazard ratio, 1.23; 95% CI, 1.01, to 1.49; P=0.04). The primary and secondary outcome results were similar in the two aspirin strata. CONCLUSIONS Administration of aspirin before surgery and throughout the early postsurgical period had no significant effect on the rate of a composite of death or nonfatal myocardial infarction but increased the risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.).

Myocardial injury after noncardiac surgery: a large, international, prospective cohort study establishing diagnostic criteria, characteristics, predictors, and 30-day outcomes.

Background:Myocardial injury after noncardiac surgery (MINS) was defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. The study’s four objectives were to determine the diagnostic criteria, characteristics, predictors, and 30-day outcomes of MINS. Methods:In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days. Patients with a troponin T level of 0.04 ng/ml or greater (elevated “abnormal” laboratory threshold) were assessed for ischemic features (i.e., ischemic symptoms and electrocardiography findings). Patients adjudicated as having a nonischemic troponin elevation (e.g., sepsis) were excluded. To establish diagnostic criteria for MINS, the authors used Cox regression analyses in which the dependent variable was 30-day mortality (260 deaths) and independent variables included preoperative variables, perioperative complications, and potential MINS diagnostic criteria. Results:An elevated troponin after noncardiac surgery, irrespective of the presence of an ischemic feature, independently predicted 30-day mortality. Therefore, the authors’ diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia. MINS was an independent predictor of 30-day mortality (adjusted hazard ratio, 3.87; 95% CI, 2.96–5.08) and had the highest population-attributable risk (34.0%, 95% CI, 26.6–41.5) of the perioperative complications. Twelve hundred patients (8.0%) suffered MINS, and 58.2% of these patients would not have fulfilled the universal definition of myocardial infarction. Only 15.8% of patients with MINS experienced an ischemic symptom. Conclusion:Among adults undergoing noncardiac surgery, MINS is common and associated with substantial mortality.

Cardiovascular Health: The Importance of Measuring Patient-Reported Health Status A Scientific Statement From the American Heart Association

The principal goals of health care are to help people “live longer and live better,” that is, to optimize both survival and health. In the American Heart Association’s (AHA) special report, “Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association’s strategic Impact Goal through 2020 and beyond,” the AHA set the following goal: > “By 2020, to improve the cardiovascular health of all Americans by 20% while reducing deaths from cardiovascular diseases and stroke by 20%.” 1 The emphasis on improving cardiovascular health is laudable, yet it raises the question of how cardiovascular health is best measured. Indeed, the metrics of cardiovascular health have not been well delineated compared with other cardiovascular mortality and morbidity outcomes. The AHA’s strategic goals primarily focus on ideal health behaviors (eg, not smoking) and ideal health factors (eg, blood pressure control) as metrics of cardiovascular health.1 Although these are of clear import, they do not directly address the World Health Organization’s definition of health as “… a state of complete physical, mental and social well-being.”2 Moreover, the Institute of Medicine identified patient-centered care as 1 of the 6 domains of high-quality health care, wherein patient-centered care supports clinicians in “attending to their patients’ physical and emotional needs, and maintaining or improving their quality of life.”3 The Patient-Centered Outcomes Research Institute emphasizes the goal of “focusing on outcomes that people notice and care about such as survival, function, symptoms, and health related quality of life.”4 Recent concepts of value in health care and the “triple aim” center on improving patients’ health and experience with health care while reducing costs; each reinforces the importance of assessing the impact of disease and medical treatment on patients’ functional status and quality of life.5,6 The definition …

Clonidine in Patients Undergoing Noncardiac Surgery

BACKGROUND Marked activation of the sympathetic nervous system occurs during and after noncardiac surgery. Low-dose clonidine, which blunts central sympathetic outflow, may prevent perioperative myocardial infarction and death without inducing hemodynamic instability. METHODS We performed a blinded, randomized trial with a 2-by-2 factorial design to allow separate evaluation of low-dose clonidine versus placebo and low-dose aspirin versus placebo in patients with, or at risk for, atherosclerotic disease who were undergoing noncardiac surgery. A total of 10,010 patients at 135 centers in 23 countries were enrolled. For the comparison of clonidine with placebo, patients were randomly assigned to receive clonidine (0.2 mg per day) or placebo just before surgery, with the study drug continued until 72 hours after surgery. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days. RESULTS Clonidine, as compared with placebo, did not reduce the number of primary-outcome events (367 and 339, respectively; hazard ratio with clonidine, 1.08; 95% confidence interval [CI], 0.93 to 1.26; P=0.29). Myocardial infarction occurred in 329 patients (6.6%) assigned to clonidine and in 295 patients (5.9%) assigned to placebo (hazard ratio, 1.11; 95% CI, 0.95 to 1.30; P=0.18). Significantly more patients in the clonidine group than in the placebo group had clinically important hypotension (2385 patients [47.6%] vs. 1854 patients [37.1%]; hazard ratio 1.32; 95% CI, 1.24 to 1.40; P<0.001). Clonidine, as compared with placebo, was associated with an increased rate of nonfatal cardiac arrest (0.3% [16 patients] vs. 0.1% [5 patients]; hazard ratio, 3.20; 95% CI, 1.17 to 8.73; P=0.02). CONCLUSIONS Administration of low-dose clonidine in patients undergoing noncardiac surgery did not reduce the rate of the composite outcome of death or nonfatal myocardial infarction; it did, however, increase the risk of clinically important hypotension and nonfatal cardiac arrest. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.).

Development and validation of a surname list to define Chinese ethnicity.

Objective:Surnames have the potential to accurately identify ancestral origins as they are passed on from generation to generation. In this study, we developed and validated a Chinese surname list to define Chinese ethnicity. Methods:We conducted a literature review, a panel review, and a telephone survey in a randomly selected sample from a Canadian city in 2003 to develop a Chinese surname list. The list was then validated to data from the Canadian Community Health Survey. Both surveys collected information on self-reported ethnicity and surname. Results:Of the 112,452 people analyzed in the Canadian Community Health Survey, 1.6% were self-reported as Chinese. This was similar to the 1.5% identified by the surname list. Compared with self-reported Chinese ethnicity (reference standard), the surname list had 77.7% sensitivity, 80.5% positive predictive value, 99.7% specificity, and 99.6% negative predictive value. When stratifying by sex and marital status, the positive predictive value was 78.9% for married women and 83.6% for never married women. Conclusions:The Chinese surname list appears to be valid in identifying Chinese ethnicity. The validity may depend on the geographic origins and Chinese dialects in given populations.

Differences in admission rates and outcomes between men and women presenting to emergency departments with coronary syndromes

Background: Previous studies examining sex-related differences in the treatment of coronary artery disease have focused on patients in hospital. We sought to examine sex-related differences at an earlier point in care — presentation to the emergency department. Methods: We collected data on ambulatory care and hospital admissions for 54 134 patients (44% women) who presented to an emergency department in Alberta between July 1998 and March 2001 because of acute myocardial infarction, unstable angina, stable angina or chest pain. We used logistic regression and Cox regression analyses to determine sex-specific associations between the likelihood of discharge from the emergency department or coronary revascularization within 1 year and 1-year mortality after adjusting for age, comorbidities and socioeconomic factors. Results: Following the emergency department visit, 91.3% of patients with acute myocardial infarction, 87.4% of those with unstable angina, 40.7% of those with stable angina and 19.8% of those with chest pain were admitted to hospital. Women were more likely than men to be discharged from the emergency department: adjusted odds ratio (and 95% confidence interval [CI]) 2.25 (1.75–2.90) for acute myocardial infarction, 1.71 (1.45–2.01) for unstable angina, 1.33 (1.15–1.53) for stable angina and 1.46 (1.36–1.57) for chest pain. Women were less likely than men to undergo coronary revascularization within 1 year: adjusted odds ratio (and 95% CI) 0.65 (0.57–0.73) for myocardial infarction, 0.39 (0.35–0.44) for unstable angina, 0.35 (0.29–0.42) for stable angina and 0.32 (0.27–0.37) for chest pain. Female sex had no impact on 1-year mortality among patients with acute myocardial infarction; it was associated with a decreased 1-year mortality among patients with unstable angina, stable angina and chest pain: adjusted hazard ratio (and 95% CI) 0.60 (0.46–0.78), 0.60 (0.46–0.78) and 0.74 (0.63–0.87) respectively. Interpretation: Women presenting to the emergency department with coronary syndromes are less likely than men to be admitted to an acute care hospital and to receive coronary revascularization procedures. These differences do not translate into worse outcomes for women in terms of 1-year mortality.

Outcomes Associated With Bilateral Internal Thoracic Artery Grafting: The Importance of Age

BACKGROUND Although bilateral internal thoracic artery (BITA) grafting in coronary artery bypass grafting (CABG) is associated with low morbidity and good long-term results, controversy exists about the age after which BITA grafting is no longer beneficial. We sought to determine if such an age cutoff point exists. METHODS The study cohort consisted of 5,601 consecutive patients from a cardiac surgery registry who underwent isolated CABG (1,038 [19%] BITA grafts, 4,029 [72%] single internal thoracic artery [SITA] grafts, 534 [10%] vein-only grafts) between 1995 and 2008. A Cox model was used to compare survival by use of bilateral, single, or no internal thoracic artery (ITA) grafts, adjusting for baseline clinical and demographic characteristics. RESULTS Mean follow-up was 7.1 years. Patients undergoing BITA grafting had the lowest 1-year mortality (2.4% versus 4.3% SITA grafting and 8.2% vein-only grafting; p < 0.0001). Relative to SITA grafting, a crude survival benefit of 54% existed for BITA grafting (hazard ratio [HR] 0.46; 95% confidence interval [CI], 0.37 to 0.57; p < 0.0001) with worse survival for vein-only grafts (HR, 1.16; 95% CI, 0.99 to 1.37; p = 0.07). After adjustment, the benefit of BITA grafting was no longer statistically significant (HR, 0.87; 95% CI, 0.69 to 1.08; p = 0.2). However age may be an effect modifier: a spline analysis plotting HR (BITA grafting versus SITA grafting) against age suggested a potential survival advantage associated with BITA grafting in patients younger than 69.9 years. CONCLUSIONS Bilateral internal thoracic artery grafting is a reasonable revascularization strategy in suitable patients up to age 70 years. As benefits of arterial grafting become more obvious over time, a longer period of follow-up will be needed to confirm the advantage of a BITA grafting strategy. In the meantime the BITA grafting advantage for patients older than 70 years is not clear.

Canadian Cardiovascular Society Guidelines on Perioperative Cardiac Risk Assessment and Management for Patients Who Undergo Noncardiac Surgery

The Canadian Cardiovascular Society Guidelines Committee and key Canadian opinion leaders believed there was a need for up to date guidelines that used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system of evidence assessment for patients who undergo noncardiac surgery. Strong recommendations included: 1) measuring brain natriuretic peptide (BNP) or N-terminal fragment of proBNP (NT-proBNP) before surgery to enhance perioperative cardiac risk estimation in patients who are 65 years of age or older, are 45-64 years of age with significant cardiovascular disease, or have a Revised Cardiac Risk Index score ≥ 1; 2) against performing preoperative resting echocardiography, coronary computed tomography angiography, exercise or cardiopulmonary exercise testing, or pharmacological stress echocardiography or radionuclide imaging to enhance perioperative cardiac risk estimation; 3) against the initiation or continuation of acetylsalicylic acid for the prevention of perioperative cardiac events, except in patients with a recent coronary artery stent or who will undergo carotid endarterectomy; 4) against α2 agonist or β-blocker initiation within 24 hours before surgery; 5) withholding angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker starting 24 hours before surgery; 6) facilitating smoking cessation before surgery; 7) measuring daily troponin for 48 to 72 hours after surgery in patients with an elevated NT-proBNP/BNP measurement before surgery or if there is no NT-proBNP/BNP measurement before surgery, in those who have a Revised Cardiac Risk Index score ≥1, age 45-64 years with significant cardiovascular disease, or age 65 years or older; and 8) initiating of long-term acetylsalicylic acid and statin therapy in patients who suffer myocardial injury/infarction after surgery.

Revascularization in patients with heart failure

Background: Although practice guidelines recommend coronary revascularization for patients with heart failure, the evidence to support this recommendation is weak. The objective of our study was to determine the association of coronary revascularization with survival in patients who have had heart failure. Methods: Data were obtained from the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH), a clinical outcome–monitoring initiative that has captured data on all patients undergoing cardiac catheterization in the province of Alberta since 1995. Our study included data from patients with a history of heart failure and with documented coronary artery disease; patients with normal coronary arteries or prior coronary artery bypass grafting (CABG) were excluded. We constructed survival curves and adjusted them by the corrected group prognosis method (incorporating all clinical variables in APPROACH). Propensity scores were used to account for clinical characteristics that could influence the decision to revascularize. Results: A total of 2538 patients (mean age 68 yr, standard deviation [SD] 11 yr, 31% female) underwent revascularization; 1690 patients (mean age 69 [SD 11] yr, 34% female) did not. Crude 1-year mortality was 11.8% among patients who underwent revascularization, compared with 21.6% among those who did not. Adjusted survival curves diverged early and continued up to 7 years of follow-up (hazard ratio 0.50, 95% confidence interval 0.44–0.57). Propensity scores showed improved survival with revascularization across all quintiles of likelihood of revascularization. Interpretation: This new evidence lends support to practice guidelines, which recommend revascularization in patients with heart failure and coronary disease.

Abciximab Attenuates Coronary Microvascular Endothelial Dysfunction After Coronary Stenting

Background—Platelet glycoprotein IIb/IIIa receptor blockade with abciximab decreases ischemic events after percutaneous coronary intervention (PCI); however, the mechanism of this benefit has not been fully elucidated. The present study was designed to assess endothelium-dependent vasomotion after coronary stenting and to determine if abciximab alters this response. Methods and Results—The study group consisted of 48 patients (59±10 years of age) with discrete coronary stenoses who underwent stenting alone (n=28) or stenting plus abciximab (n=20). A control group consisted of 31 additional patients who had vasomotor testing on a non-PCI vessel. Coronary blood flow (CBF) was measured (0.014-inch Doppler wire) 30 minutes after uncomplicated PCI and in response to the intracoronary infusion of acetylcholine (Ach) (10−7, 10−6 mol/L Ach) and adenosine (24 &mgr;g). Ach-mediated increase in CBF was impaired after stent insertion when compared with the control group (41±52% versus 70±48%;P <0.05). The stenting plus abciximab group demonstrated a superior CBF response to Ach compared with the stenting alone group (83±93% versus 41±52%;P <0.05), with no difference between groups in the peak flow or percent change in flow to adenosine. By multivariate analysis, concomitant administration of abciximab was strongly predictive of the change in CBF to Ach (P <0.005). Conclusions—Abciximab preserves the CBF response to Ach after coronary stenting. The preservation of microvascular endothelial function may help explain the beneficial clinical effect of this agent in patients undergoing PCI.