Pulse pressure in acute coronary syndromes: Comparative prognostic significance with systolic blood pressure.

BACKGROUND: Pulse pressure is a readily available vital sign that has been shown to independently predict outcomes in several cardiovascular disease states. We investigated the prognostic significance of pulse pressure (PP) and systolic blood pressure (SBP) among patients with acute coronary syndromes (ACS). METHODS: A total of 14,514 patients with ACS in the prospective, multicentre Global Registry of Acute Coronary Events (GRACE), expanded GRACE (GRACE-2) and Canadian Registry of Acute Coronary Events (CANRACE) were stratified by initial PP on presentation. Patient characteristics and in-hospital outcomes were compared by PP quartiles and the independent prognostic significance of PP for in-hospital mortality was quantified. We compared the discriminative ability (c-statistic) of models incorporating either PP or SBP. RESULTS: Patients with higher PPs were older, more frequently female and had higher prevalence rates of conventional cardiovascular risk factors (all p < 0.01). Lower PP was associated with ST-segment elevation myocardial infarction presentation, higher GRACE risk scores and higher rates of adverse in-hospital outcomes (p < 0.001). PP was strongly correlated with SBP (Pearson's correlation coefficient = 0.79, p < 0.001). After adjustment for other GRACE risk model predictors, lower PP was independently associated with in-hospital mortality (first vs. fourth quartile [reference]: adjusted odds ratio 2.57, 95% confidence interval 1.80-3.67). The c-statistic was slightly higher for the multivariable model incorporating SBP as compared to the model with PP (0.868 vs. 0.864, respectively, p = 0.028) for in-hospital mortality. CONCLUSION: Higher presenting PP is associated with increased age and more prevalent cardiovascular risk factors, whereas patients with lower PP present with worse clinical characteristics and in-hospital outcomes. Lower PP is an independent adverse prognosticator in ACS. However, PP did not improve the discriminatory performance of the GRACE risk score compared with SBP.

Smoking abstinence 1 year after acute coronary syndrome: follow-up from a randomized controlled trial of varenicline in patients admitted to hospital.

BACKGROUND: Patients who continue to smoke after acute coronary syndrome are at increased risk of reinfarction and death. We previously found use of varenicline to increase abstinence 24 weeks after acute coronary syndrome; here we report results through 52 weeks. METHODS: The EVITA trial was a multicentre, double-blind, randomized, placebo-controlled trial of varenicline for smoking cessation in patients admitted to hospital with acute coronary syndrome. Participants were randomly assigned (1:1) to receive varenicline or placebo for 12 weeks, in conjunction with low-intensity counselling. Smoking abstinence was assessed via 7-day recall, with biochemical validation using exhaled carbon monoxide. Participants lost to follow-up or withdrawn were assumed to have returned to smoking. RESULTS: Among the 302 participants, abstinence declined over the course of the trial, with 34.4% abstinent 52 weeks after acute coronary syndrome. Compared with placebo, point estimates suggest use of varenicline increased point-prevalence abstinence (39.9% v. 29.1%, difference 10.7%, 95% confidence interval [CI] 0.01% to 21.44%; number needed to treat 10), continuous abstinence (31.1% v. 21.2%, difference 9.9%, 95% CI -0.01% to 19.8%) and reduction in daily cigarette smoking by 50% or greater (57.8% v. 49.7%, difference 8.1%, 95% CI -3.1% to 19.4%). Varenicline and placebo groups had similar occurrence of serious adverse events (24.5% v. 21.9%, risk difference 2.7%, 95% CI -7.3% to 12.6%) and major adverse cardiovascular events (8.6% v. 9.3%, risk difference -0.7%, 95% CI -7.8% to 6.5%). INTERPRETATION: Varenicline was efficacious for smoking cessation in this high-risk patient population. However, 60% of patients who received treatment with varenicline still returned to smoking. Trial registration: ClinicalTrials.gov, no. NCT00794573.

Smokers and Postcessation Weight Gain After Acute Coronary Syndrome.

BACKGROUND: Smoking cessation and weight management are recommended after acute coronary syndrome (ACS); however, little is known about the effects of smoking cessation on weight change after ACS. We aimed to assess the effect of smoking cessation after ACS on weight over a 12-month follow-up period. METHODS AND RESULTS: Data were prospectively collected from the EVITA (Evaluation of Varenicline in Smoking Cessation for Patients Post-Acute Coronary Syndrome) trial. Weight change was compared among 3 groups of patients: those who were completely abstinent (n=70), those who smoked intermittently (n=68), and those who smoked persistently (n=34). Patients' mean baseline weight was 83.9 kg (SD 17.7) with a mean body mass index of 28.5 (SD 5.4). Patients smoked a mean of 37.7 years (SD 17.7) and a mean of 21.0 cigarettes (SD 9.0) per day prior to their ACS. Weight change varied across groups, with abstainers gaining a mean of 4.8 kg (SD 8.6), intermittent smokers gaining a mean of 2.0 kg (SD 8.9) and persistent smokers losing a mean of 0.7 kg (SD 7.4). At 52 weeks, abstainers were more likely to gain weight than persistent smokers (difference in means 5.5 kg; 95% CI 2.3-8.8). This weight gain was not associated with an increase in the use of antihypertensive or antidiabetic medications. CONCLUSIONS: Following an ACS, significant weight is gained by patients who quit smoking. Weight-management interventions among smokers who quit after ACS should be a focus of investigation in future research so that the cardiovascular benefits achieved by smoking cessation are not offset by weight gain in this high-risk population. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794573.

In-hospital management and outcomes of acute coronary syndromes in relation to prior history of heart failure.

INTRODUCTION: The prognostic significance of prior heart failure in acute coronary syndromes has not been well studied. Accordingly, we evaluated the baseline characteristics, management patterns and clinical outcomes in patients with acute coronary syndromes who had prior heart failure. METHODS AND RESULTS: The study population consisted of acute coronary syndrome patients in the Global Registry of Acute Coronary Events, expanded Global Registry of Acute Coronary Events and Canadian Registry of Acute Coronary Events between 1999 and 2008. Of the 13,937 eligible patients (mean age 66±13 years, 33% female and 28.3% with ST-elevation myocardial infarction), 1498 (10.7%) patients had a history of heart failure. Those with prior heart failure tended to be older, female and had lower systolic blood pressure, higher Killip class and creatinine on presentation. Prior heart failure was also associated with significantly worse left ventricular systolic function and lower rates of cardiac catheterization and coronary revascularization. The group with previous heart failure had significantly higher rates of acute decompensated heart failure, cardiogenic shock, myocardial (re)infarction and mortality in hospital. In multivariable analysis, prior heart failure remained an independent predictor of in-hospital mortality (odds ratio 1.48, 95% confidence interval 1.08-2.03, p=0.015). CONCLUSIONS: Prior heart failure was associated with high risk features on presentation and adverse outcomes including higher adjusted in-hospital mortality in acute coronary syndrome patients. However, acute coronary syndrome patients with prior heart failure were less likely to receive evidence-based therapies, suggesting potential opportunities to target more intensive treatment to improve their outcome.

Varenicline for Smoking Cessation in Hospitalized Patients With Acute Coronary Syndrome.

BACKGROUND: Less than one-third of smokers hospitalized with an acute coronary syndrome (ACS) remain abstinent following discharge. We assessed whether varenicline, begun in-hospital, is efficacious for smoking cessation following ACS. METHODS AND RESULTS: We conducted a multi-center, double-blind, randomized, placebo-controlled trial in which smokers hospitalized with an ACS were randomized to varenicline or placebo for 12 weeks. All patients received low-intensity counseling. The primary end point was point-prevalence smoking abstinence assessed at 24 weeks by 7-day recall and biochemical validation using expired carbon monoxide. A total of 302 patients were randomized (mean age 55±9 years; 75% male; 56% ST-segment elevation myocardial infarction; 38% non-ST-segment elevation myocardial infarction; 6% unstable angina). Patients smoked a mean of 21±11 cigarettes/d at the time of hospitalization and had been smoking for a mean of 36±12 years. At 24 weeks, patients randomized to varenicline had significantly higher rates of smoking abstinence and reduction than patients randomized to placebo. Point-prevalence abstinence rates were 47.3% in the varenicline group and 32.5% in the placebo group (P=0.012; number needed to treat=6.8). Continuous abstinence rates were 35.8% and 25.8%, respectively (P=0.081; number needed to treat=10.0), and rates of reduction ≥50% in daily cigarette consumption were 67.4% and 55.6%, respectively (P=0.05; number needed to treat=8.5). Adverse event rates within 30 days of study drug discontinuation were similar between groups (serious adverse events: varenicline 11.9%, placebo 11.3%; major adverse cardiovascular events: varenicline 4.0%, placebo 4.6%). CONCLUSIONS: Varenicline, initiated in-hospital following ACS, is efficacious for smoking cessation. Future studies are needed to establish safety in these patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794573.

Weight change in patients attempting to quit smoking post-myocardial infarction.

BACKGROUND: Current guidelines recommend smoking cessation and weight management for secondary prevention in patients post-myocardial infarction. However, little is known about the effects of smoking cessation on weight change post-myocardial infarction. METHODS: We examined patterns of weight change and its effects on blood pressure and glycemic control using data from a randomized trial investigating the effect of bupropion on smoking cessation in patients post-myocardial infarction. Weight change was compared among 3 groups of patients: those who were completely abstinent (n = 92), those who smoked intermittently (n = 49), and those who smoked persistently (n = 38) during the 12-month follow-up. Analyses were restricted to patients who attended all follow-up visits. RESULTS: The median weight at baseline was 77.1 kg (interquartile range [IQR], 66.0, 87.5), and 64.3% of patients were overweight/obese (body mass index ≥25.0 kg/m(2)). The median weight gain at 12 months was 4.0 kg (IQR, 0-7.0), with more than one third gaining >5 kg. The proportion of patients who were overweight/obese increased by approximately 10%, and 23.2% of patients moved up a body mass index category. Abstainers gained a median of 4.8 kg (IQR, 1.0, 8.6), intermittent smokers gained a median of 2.0 kg (IQR, -2.0, 5.0), and persistent smokers gained a median of 3.0 kg (IQR, -0.8, 6.0). Weight gain was associated with an increase in blood pressure and requirements for hypoglycemic medications at 12 months. CONCLUSIONS: The majority of patients attempting to quit smoking gain weight 12 months post-myocardial infarction, with abstainers gaining more weight than those who return to smoking. Weight gain was associated with an increased prevalence of hypertension and diabetes.

Use and timing of coronary angiography and associated in-hospital outcomes in Canadian non-ST-segment elevation myocardial infarction patients: insights from the Canadian Global Registry of Acute Coronary Events.

BACKGROUND: Although an early invasive approach has become standard strategy for the management of non-ST-segment elevation myocardial infarction (NSTEMI), the frequency and timing in Canada is uncertain. METHODS: We examined the use and timing of coronary angiography, revascularization, and cardiovascular outcomes of NSTEMI patients: (1) admitted on weekdays vs weekends; and (2) stratified according to presentation risk level, in the Canadian Global Registry of Acute Coronary Events (GRACE)/Expanded GRACE (GRACE(2))/Canadian Registry of Acute Coronary Events (CANRACE) population. RESULTS: Of 6711 NSTEMI patients, 1956 (29.1%) were admitted on the weekend. The median (interquartile range) wait time for coronary angiography was 58 (32-106) and 70 (50-112) hours for weekday and weekend patients, respectively (P = 0.32). Compared with lower-intermediate risk, higher-risk patients were less likely to undergo angiography (44.7% vs 69.7% for weekdays and 45.2% vs 69.6% for weekends; both P < 0.0001) and waited longer for angiography (median 71 vs 61 hours; P < 0.0001). Weekend admission was independently associated with higher mortality (adjusted odds ratio [OR], 1.52; 95% confidence interval [CI], 1.15-2.01; P = 0.004), recurrent ischemia (adjusted OR, 1.16; 95% CI, 1.01-1.32; P = 0.03), and heart failure (adjusted OR, 1.28; 95% CI, 1.00-1.63; P = 0.048) but not with reinfarction. CONCLUSIONS: Median wait time for angiography in Canadian NSTEMI patients admitted on the weekend was not significantly longer than for those who presented on a weekday. Patients admitted on weekends had higher adjusted mortality and cardiovascular event rates. Higher-risk patients were less likely to undergo angiography and waited longer, with higher observed in-hospital event rates. Systematic, guideline-recommended risk stratification should be considered to ensure that optimal management strategies (eg, timely coronary angiography in higher-risk patients) are matched to level of risk.

Treatment and outcomes of non-ST elevation acute coronary syndromes in relation to burden of pre-existing vascular disease.

BACKGROUND: Patients with atherosclerotic disease in one territory often have disease in other vascular territories. However, the relationships between pre-existing vascular disease and the treatment and outcome of acute coronary syndrome (ACS), have not been well characterized. METHODS: The Canadian ACS2, Global Registry of Acute Coronary Events (GRACE/GRACE(2)), and Canadian Registry of Acute Coronary Events (CANRACE) were used to obtain data on 10,667 non-ST segment elevation acute coronary syndrome (NSTEACS) patients between 2002 and 2008. Multivariable analysis was used to examine the relationships between the number of vascular beds affected and both in-hospital coronary angiography and in-hospital mortality. The ACS2 registry (2002-2003) included physician-reported reasons for non-invasive management, which were stratified by vascular disease burden. RESULTS: Patients with more vascular disease had higher GRACE risk scores at presentation, but less frequently received antiplatelet agents and angiography. The most common reason in the ACS2 registry for patients who did not undergo angiography was "not high enough risk." There was an independent inverse relationship between the extent of vascular disease and in-hospital angiography. Patients with higher vascular disease burden had higher unadjusted in-hospital mortality. In multivariable analysis, patients with 1 vascular territory affected had the lowest and those with 3 vascular beds affected had the highest adjusted in-hospital mortality. In the ACS2 registry, patients with more extensive vascular disease had higher rates of 1-year mortality and death/re-infarction (both p for trend <0.001). CONCLUSIONS: NSTEACS patients with more vascular disease received less intensive treatment, with an associated worse outcome. This undertreatment might be partly mediated by physicians' underestimation of patient risk. More aggressive risk factor modification and intensive ACS therapies may improve the outcome of these high-risk patients.

Treatment and outcomes of patients with suspected acute coronary syndromes in relation to initial diagnostic impressions (insights from the Canadian Global Registry of Acute Coronary Events [GRACE] and Canadian Registry of Acute Coronary Events [CANRACE]).

The early diagnosis of acute coronary syndrome (ACS) remains challenging, and a considerable proportion of patients are diagnosed with "possible" ACS on admission. The Global Registry of Acute Coronary Events (GRACE/GRACE(2)) and Canadian Registry of Acute Coronary Events (CANRACE) enrolled 16,618 Canadian patients with suspected ACS in 1999 to 2008. We compared the demographic and clinical characteristics, use of cardiac procedures, prognostic accuracy of the GRACE risk score, and in-hospital outcomes between patients given an admission diagnosis of "definite" versus "possible" ACS by the treating physician. Overall, 11,152 and 5,466 patients were given an initial diagnosis of "definite" ACS and "possible" ACS, respectively. Patients with a "possible" ACS had higher GRACE risk score (median 130 vs 125) and less frequently received aspirin, clopidogrel, heparin, or ß blockers within the first 24 hours of presentation and assessment of left ventricular function, stress testing, cardiac catheterization, and percutaneous coronary intervention (all p <0.05). Patients with "possible" ACS had greater rates of in-hospital myocardial infarction (9.0% vs 2.0%, p <0.05) and heart failure (12% vs 8.9%, p <0.05). The GRACE risk score demonstrated excellent discrimination for in-hospital mortality in both groups and for the entire study population. In conclusion, compared to patients with "definite" ACS on presentation, those with "possible" ACS had higher baseline GRACE risk scores but less frequently received evidence-based medical therapies within 24 hours of admission or underwent cardiac procedures during hospitalization. The GRACE risk score provided accurate risk assessment, regardless of the initial diagnostic impression.

Management and outcome of acute coronary syndrome patients in relation to prior history of atrial fibrillation.

BACKGROUND: The prognostic impact of atrial fibrillation (AF) in the setting of acute coronary syndrome (ACS) is controversial. Furthermore, there are limited real-world data on the management of ACS patients with history of AF. METHODS: The Global Registry of Acute Coronary Events (GRACE/GRACE2) and Canadian Registry of Acute Coronary Events (CANRACE) enrolled 14,285 patients across Canada between 1999 and 2008. Patients were stratified by the presence of history of AF. We compared clinical characteristics, medical therapies, cardiac procedures, and clinical outcomes between the 2 groups. RESULTS: Overall, 1333 of the enrolled patients (9.3%) had history of AF, of whom 51.5% presented with non-ST-segment elevation myocardial infarction, 29.5% with unstable angina, and 19.1% with ST-segment elevation myocardial infarction. Compared with the group without, patients with a history of AF less frequently received evidence-based antiplatelet and antithrombin therapies, left ventricle ejection fraction assessment, and coronary angiography (all P < 0.001); they also had higher unadjusted rates of in-hospital death, myocardial (re)infarction, and heart failure. However, in multivariable analysis, history of AF was not found to be independently associated with in-hospital mortality (adjusted odds ratio [OR] = 1.12; 95% confidence interval (CI), 0.73-1.73; P = 0.61) or death and/or myocardial reinfarction (adjusted OR = 1.15; 95% CI, 0.87-1.5; P = 0.34). CONCLUSIONS: History of AF is common among ACS patients. They received less evidence-based medical and invasive therapies than ACS patients without history of AF. History of AF is a negative independent predictor of in-hospital coronary angiography but was not found to be independently associated with adverse outcomes.

Temporal patterns of lipid testing and statin therapy in acute coronary syndrome patients (from the Canadian GRACE Experience).

Current guidelines recommend the measurement of fasting lipid profile and use of statins in all patients with acute coronary syndrome (ACS). However, the temporal trends of lipid testing and statin therapy in "real-world" patients with ACS are unclear. From January 1999 through December 2008, the prospective, multicenter, Global Registry of Acute Coronary Events (GRACE/GRACE(2)/CANRACE) enrolled 13,947 patients with ACS in Canada. We stratified the study population based on year of presentation into 3 groups (1999 to 2004, 2005 to 2006, and 2007 to 2008) and compared the use of lipid testing and use of statin therapy in hospital. Overall, 70.8% of patients underwent lipid testing and 79.4% received in-hospital statin therapy; these patients were younger and had lower GRACE risk scores (p <0.001 for the 2 comparisons) compared to those who did not. Over time there was a significant increase in rates of in-hospital statin therapy (70% in 1999 to 2004 to 84.5% in 2007 to 2008, p for trend < 0.001) but only a minor increase in rates of lipid testing (69.4% in 1999 to 2004 to 72.4% in 2007 to 2008, p for trend = 0.003). After adjusting for confounders, this increasing temporal trend remained statistically significant for statin therapy (p <0.001) but not for lipid testing. Lipid testing was independently associated with in-hospital statin use (adjusted odds ratio 1.62, 95% confidence interval 1.27 to 2.08, p <0.001). In patients who did have lipid testing, those with low-density lipoprotein cholesterol level >130 mg/dl (3.4 mmol/L) were more likely to be treated with in-hospital statins. In conclusion, there has been a significant temporal increase in the use of in-hospital statin therapy but only a minor increase in lipid testing. Lipid testing was strongly associated with in-hospital statin use. A substantial proportion of patients with ACS, especially those at higher risk, still do not receive these guideline-recommended interventions in contemporary practice.

Bridging the gender gap: Insights from a contemporary analysis of sex-related differences in the treatment and outcomes of patients with acute coronary syndromes.

BACKGROUND: The question of whether gender-related disparities still exist in the treatment and outcomes of patients presenting with acute coronary syndromes (ACS) remains controversial. Using data from 4 registries spanning a decade, we sought to determine whether sex-related differences have persisted over time and to examine the treating physician's rationale for adopting a conservative management strategy in women compared with men. METHODS: From 1999 to 2008, 14,196 Canadian patients with non-ST-segment elevation ACS were recruited into the Acute Coronary Syndrome I (ACSI), ACSII, Global Registry of Acute Coronary Events (GRACE/GRACE(2)), and Canadian Registry of Acute Coronary Events (CANRACE) prospective multicenter registries. RESULTS: Women in the study population were found to be significantly older than men and were more likely to have a history of heart failure, diabetes, or hypertension. Fewer women were treated with thienopyridines, heparin, and glycoprotein IIb/IIIa inhibitors compared with men in GRACE and CANRACE. Female gender was independently associated with a lower in-hospital use of coronary angiography (adjusted odds ratio 0.76, 95% CI 0.69-0.84, P < .001) and higher in-hospital mortality (adjusted odds ratio 1.26, 95% CI 1.02-1.56, P = .036), irrespective of age (P for interaction =.76). Underestimation of patient risk was the most common reason for not pursuing an invasive strategy in both men and women. CONCLUSIONS: Despite temporal increases in the use of invasive cardiac procedures, women with ACS are still more likely to be treated conservatively, which may be due to underestimation of patient risk. Furthermore, they have worse in-hospital outcomes. Greater awareness of this paradox may assist in bridging the gap between current guidelines and management practices.

Relation between previous angiotensin-converting enzyme inhibitor use and in-hospital outcomes in acute coronary syndromes.

Angiotensin-converting enzyme (ACE) inhibitor use in patients at high risk of coronary artery disease has been associated with a decrease in the risk of myocardial infarction (MI) and death. However, it is unclear whether chronic use of these agents modifies the course and outcome of an acute coronary syndrome (ACS). This study assessed the association between chronic use of ACE inhibitors and clinical outcomes in patients with ACS. From 1999 through 2008, 13,632 Canadian patients with ACS were identified in the Global Registry of Acute Coronary Events (GRACE), the expanded GRACE (GRACE(2)), and the Canadian Registry of Acute Coronary Events (CANRACE). Patients were stratified by previous use of an ACE inhibitor. Clinical characteristics, in-hospital treatment, and outcomes were compared between the 2 groups. Multivariable logistic regression analysis adjusting for GRACE risk score and other clinical factors was performed. Patients receiving an ACE inhibitor before the ACS had a higher prevalence of diabetes (40.6% vs 21.2%, p <0.001), previous MI (51.8% vs 23.3%, p <0.001), heart failure (18.0% vs 6.9%), and higher GRACE scores at presentation (133 vs 124, p <0.001). Multivariable analysis demonstrated no significant association between previous ACE inhibitor use and death (adjusted odds ratio [OR] 1.15, confidence interval [CI] 0.90 to 1.49, p = 0.27), in-hospital re-MI (adjusted OR 0.99, CI 0.78 to 1.25, p = 0.91), or the composite end point of death/re-MI (adjusted OR 1.01, CI 0.84 to 1.20, p = 0.94). In conclusion, previous use of an ACE inhibitor is not independently associated with improved in-hospital outcomes after an ACS.

Reperfusion strategies and outcomes of ST-segment elevation myocardial infarction patients in Canada: observations from the Global Registry of Acute Coronary Events (GRACE) and the Canadian Registry of Acute Coronary Events (CANRACE).

BACKGROUND: We examine the clinical characteristics and outcomes of ST-elevation myocardial infarction (STEMI) patients receiving various reperfusion therapies in 2 contemporary Canadian registries. METHODS: Of 4045 STEMI patients, 2024 received reperfusion therapy and had complete data on invasive management. They were stratified by reperfusion strategy used: primary percutaneous coronary intervention (PCI) (n = 716); fibrinolysis with rescue PCI (n = 177); fibrinolysis with urgent/elective PCI (n = 210); and fibrinolysis without PCI (n = 921). Data were collected on clinical and laboratory findings, and outcomes. RESULTS: Compared with fibrinolytic-treated patients, patients treated with primary PCI were younger and had higher Killip class, had longer time to delivery of reperfusion therapy, and utilized more antiplatelet therapy but less heparin, ß-blockers and angiotensin-converting enzyme inhibitors. In-hospital death occurred in 2.7% of patients treated with primary PCI, 1.7% fibrinolysis-rescue PCI, 1.0% fibrinolysis-urgent/elective PCI, and 4.8% fibrinolysis-alone (P = 0.009); the rates of death/reinfarction were 3.9%, 4.0%, 4.3%, and 7.1% (P = 0.032), respectively. The rate of shock was highest in the primary PCI group. Rates of heart failure or major bleeding were similar in the 4 groups. In multivariable analysis, no PCI during hospitalization was associated with death and reinfarction (adjusted odds ratio = 1.66; 95% confidence interval, 1.03-2.70; P = 0.04). CONCLUSIONS: Clinical features, time to reperfusion, and medication utilization differed with respect to the reperfusion strategy. While low rates of re-infarction/death were observed, these complications occurred more frequently in those who did not undergo PCI during index hospitalization.

Disparities in management patterns and outcomes of patients with non-ST-elevation acute coronary syndrome with and without a history of cerebrovascular disease.

Cerebrovascular (CVD) disease is commonly associated with coronary artery disease and adversely affects outcome. The goal of the present study was to examine the temporal management patterns and outcomes in relation to previous CVD in a contemporary "real-world" spectrum of patients with acute coronary syndrome (ACS). From 1999 to 2008, 14,070 patients with non-ST-segment elevation ACS were recruited into the Canadian Acute Coronary Syndrome I (ACS I), ACS II, Global Registry of Acute Coronary Events (GRACE/GRACE(2)), and Canadian Registry of Acute Coronary Events (CANRACE) prospective multicenter registries. We stratified the study patients according to a history of CVD and compared their treatment and outcomes. Patients with a history of CVD were older, more likely to have pre-existing coronary artery disease, elevated creatinine, higher Killip class, and ST-segment deviation on admission. Despite presenting with greater GRACE risk scores (137 vs 117, p <0.001), patients with previous CVD were less likely to receive evidence-based antiplatelet and antithrombin therapies during the initial 24 hours of hospital admission. They were also less likely to undergo in-hospital coronary angiography and revascularization. These disparities in medical and invasive management were preserved temporally across all 4 registries. Patients with concomitant CVD had worse in-hospital outcomes. Previous CVD remained an independent predictor of in-hospital mortality (adjusted odds ratio 1.43, 95% confidence interval 1.06 to 1.92, p = 0.019) after adjusting for other powerful prognosticators in the GRACE risk score. However, it was independently associated with a lower use of in-hospital coronary angiography (adjusted odds ratio 0.70, 95% confidence interval 0.60 to 0.83, p <0.001). Underestimation of patient risk was the most common reason for not pursuing an invasive strategy. Revascularization was independently associated with lower 1-year mortality (adjusted odds ratio 0.48, 95% confidence interval 0.33 to 0.71, p <0.001), irrespective of a history of CVD. In conclusion, for patients presenting with non-ST-segment elevation-ACS, a history of CVD was independently associated with worse outcomes, which might have been, in part, because of the underuse of evidence-based medical and invasive therapies.

Evaluation of left ventricular ejection fraction in non-ST-segment elevation acute coronary syndromes and its relationship to treatment.

BACKGROUND: In-hospital assessment of left ventricular ejection fraction (LVEF) in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is emphasized in current practice guidelines. There are limited data regarding the evaluation of LVEF and clinical characteristics and in-hospital management in the "real world." METHODS: Registries including the Canadian Acute Coronary Syndrome (ACS) I and II, Global Registry of Acute Coronary Events (main GRACE/expanded GRACE(2)), and Canadian Registry of Acute Coronary Events (CANRACE) enrolled 13,703 NSTE-ACS patients across Canada between 1999 and 2008. Patients were stratified by in-hospital LVEF measurement, and LVEF was categorized as normal, mildly, or moderately to severely impaired. We compared clinical characteristics, cardiac procedures, and clinical outcomes across these groups. Multivariable logistic regression identified factors independently associated with the assessment of LVEF. RESULTS: Overall, 8,116 patients (59.2%) had LVEF measurement, and of the 7,667 patients with available LVEF data, 4,470 (58.3%) had normal, 1,916 (25%) mildly impaired, and 1,281 (16.7%) moderately to severely impaired LVEF. Patients with LVEF assessment more frequently (all P < .001) underwent cardiac catheterization, percutaneous coronary intervention or coronary bypass surgery, and had higher (both P < .001) rates of myocardial (re) infarction and heart failure. In-hospital reinfarction, higher Killip class, abnormal biomarker, hospital stay >10 days, and on-site cardiac catheterization facility were independently associated with LVEF assessment. Despite increasing LVEF assessment over time (P for trend < .001), 31.2% of patients in the most recent registry (2008) had no in-hospital LVEF assessment. CONCLUSIONS: In-hospital LVEF assessment is not performed in many NSTE-ACS patients. The LVEF assessment, associated with increased use of evidence-based therapies and invasive cardiac procedures, was obtained more frequently in patients with myocardial (re) infarction, heart failure on presentation, and prolonged hospital stay.

Validation of the Global Registry of Acute Coronary Event (GRACE) risk score for in-hospital mortality in patients with acute coronary syndrome in Canada.

BACKGROUND: The Global Registry of Acute Coronary Event (GRACE) risk score was developed in a large multinational registry to predict in-hospital mortality across the broad spectrum of acute coronary syndromes (ACS). Because of the substantial regional variation and temporal changes in patient characteristics and management patterns, we sought to validate this risk score in a contemporary Canadian population with ACS. METHODS: The main GRACE and GRACE(2) registries are prospective, multicenter, observational studies of patients with ACS (June 1999 to December 2007). For each patient, we calculated the GRACE risk score and evaluated its discrimination and calibration by the c statistic and the Hosmer-Lemeshow goodness-of-fit test, respectively. To assess the impact of temporal changes in management on the GRACE risk score performance, we evaluated its discrimination and calibration after stratifying the study population into prespecified subgroups according to enrollment period, type of ACS, and whether the patient underwent coronary angiography or revascularization during index hospitalization. RESULTS: A total of 12,242 Canadian patients with ACS were included; the median GRACE risk score was 127 (25th and 75th percentiles were 103 and 157, respectively). Overall, the GRACE risk score demonstrated excellent discrimination (c statistic 0.84, 95% CI 0.82-0.86, P < .001) for in-hospital mortality. Similar results were seen in all the subgroups (all c statistics >/=0.8). However, calibration was suboptimal overall (Hosmer-Lemeshow P = .06) and in various subgroups. CONCLUSIONS: GRACE risk score is a valid and powerful predictor of adverse outcomes across the wide range of Canadian patients with ACS. Its excellent discrimination is maintained despite advances in management over time and is evident in all patient subgroups. However, the predicted probability of in-hospital mortality may require recalibration in the specific health care setting and with advancements in treatment.

Temporal trends and patterns of early clopidogrel use across the spectrum of acute coronary syndromes.

BACKGROUND: Randomized trials have established efficacy of clopidogrel in various types of acute coronary syndromes (ACS). The objective of this study was to examine the temporal trends and patterns of early clopidogrel use (within the first 24 hours of hospitalization) across the spectrum of patients with ACS in Canada. METHODS: Using the multinational, prospective GRACE (Global Registry of Acute Coronary Events) and GRACE(2), we identified 11,177 patients who were admitted for ACS from January 2003 to December 2007 in Canada. Demographic information, clinical features, and treatment were recorded. We examined the early use of clopidogrel over time and in relation to the type of ACS, clinical features on presentation, and the mode of reperfusion therapy. RESULTS: Of the 11,177 patients with ACS, 3,091 (27.7%) had ST-elevation myocardial infarction (STEMI), 5,194 (46.5%) had non-STEMI, and 2,892 (25.9%) had unstable angina; the rates of early clopidogrel administration were 63.0%, 66.6%, and 57.2%, respectively (P < .001). Overall, there was a significant increase in clopidogrel use over the period studied (P for trend < .001). In patients with non-ST-elevation ACS (non-STEMI and unstable angina), clopidogrel use was higher among those with positive cardiac biomarkers compared to those without (67.1% vs 59.8%, P < .001) but similar in the groups with and without ST deviation. There was an inverse relationship between GRACE risk score and rates of early clopidogrel administration. In patients with STEMI receiving fibrinolytic therapy, only 55.7% of patients <65 years old received clopidogrel compared with 47.0% and 42.6% of patients 65 to 74 and >75 years old, respectively (P for trend < .001). CONCLUSIONS: Although early use of clopidogrel therapy has increased over time across the spectrum of ACS, a significant proportion of eligible patients still do not receive this evidence-based therapy. There is a need to optimize the use of proven antiplatelet therapies to improve clinical outcome.