Comparison of coronary artery bypass surgery and percutaneous coronary intervention in patients with diabetes: a meta-analysis of randomised controlled trials.

BACKGROUND: The choice between coronary artery bypass surgery (CABG) and percutaneous coronary intervention (PCI) for revascularisation in patients with diabetes and multivessel coronary artery disease, who account for 25% of revascularisation procedures, is much debated. We aimed to assess whether all-cause mortality differed between patients with diabetes who had CABG or PCI by doing a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing CABG with PCI in the modern stent era. METHODS: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from Jan 1, 1980, to March 12, 2013, for studies reported in English. Eligible studies were those in which investigators enrolled adult patients with diabetes and multivessel coronary artery disease, randomised them to CABG (with arterial conduits in at least 80% of participants) or PCI (with stents in at least 80% of participants), and reported outcomes separately in patients with diabetes, with a minimum of 12 months of follow-up. We used random-effects models to calculate risk ratios (RR) and 95% CIs for pooled data. We assessed heterogeneity using I(2). The primary outcome was all-cause mortality in patients with diabetes who had CABG compared with those who had PCI at 5-year (or longest) follow-up. FINDINGS: The initial search strategy identified 3414 citations, of which eight trials were eligible. These eight trials included 7468 participants, of whom 3612 had diabetes. Four of the RCTs used bare metal stents (BMS; ERACI II, ARTS, SoS, MASS II) and four used drug-eluting stents (DES; FREEDOM, SYNTAX, VA CARDS, CARDia). At mean or median 5-year (or longest) follow-up, individuals with diabetes allocated to CABG had lower all-cause mortality than did those allocated to PCI (RR 0.67, 95% CI 0.52-0.86; p=0.002; I(2)=25%; 3131 patients, eight trials). Treatment effects in individuals without diabetes showed no mortality benefit (1.03, 0.77-1.37; p=0.78; I(2)=46%; 3790 patients, five trials; p interaction=0.03). We identified no differences in outcome whether PCI was done with BMS or DES. When present, we identified no clear causes of heterogeneity. INTERPRETATION: In the modern era of stenting and optimum medical therapy, revascularisation of patients with diabetes and multivessel disease by CABG decreases long-term mortality by about a third compared with PCI using either BMS or DES. CABG should be strongly considered for these patients.

Assessment and management of acute coronary syndromes (ACS): a Canadian perspective on current guideline-recommended treatment--part 1: non-ST-segment elevation ACS.

Despite the reduction of coronary heart disease mortality over the past 40 years, hospital admissions for acute coronary syndromes (ACS) continue to increase. The goal of this 2-part article is to review the issues at each stage of assessment and management of the ACS patient, and to propose an optimal treatment strategy for the individual patient in the context of the realities, culture, and delivery of healthcare in Canada. ACS patients are categorized as either ST segment elevation myocardial infarction (STEMI) or non-ST-elevation ACS (NSTE-ACS). For the patients with NSTE-ACS, prevention of recurrent ischemic events is the primary goal. Assessment of risk for recurrent ischemic and bleeding events helps to determine the net benefit of early cardiac catheterization and percutaneous coronary intervention (PCI) and intensive antiplatelet and anticoagulant treatment. Those with higher ischemic risk features should be considered for an early invasive strategy and receive both dual antiplatelet therapy and an anticoagulant at the time of first medical assessment. Patients without high-risk features could be considered for medical treatment and a selectively invasive strategy; with coronary angiography and revascularization only if high-risk features become apparent. Long-term vascular protection with lifestyle modification (especially smoking cessation), lipid lowering, blood pressure and glycemic control, and the use of renin angiotensin aldosterone system (RAAS) blockade to prevent recurrent ischemic events, is important in all patients with ACS.

Implications of variability in definition and reporting of major bleeding in randomized trials of oral P2Y12 inhibitors for acute coronary syndromes.

AIMS: Various definitions of major bleeding have been used to evaluate safety in randomized controlled trials of antiplatelet therapy. We compared the definitions and rates of major bleeding in phase III randomized controlled trials of oral P2Y(12) inhibitors in the management of patients with acute coronary syndromes (ACS). METHODS AND RESULTS: Electronic searches identified six phase III randomized controlled oral P2Y(12) inhibitor trials published between 2001 and 2010 involving 119 020 patients with ACS. The trials compared clopidogrel standard-dose (300-mg loading dose, 75-mg daily thereafter) vs. placebo (CURE, CLARITY-TIMI 28, COMMIT), clopidogrel standard-dose vs. prasugrel (TRITON-TIMI 38) or ticagrelor (PLATO) and clopidogrel standard-dose vs. clopidogrel double-dose (600-mg loading dose, 150-mg daily for 6-days, 75-mg daily thereafter) (CURRENT-OASIS 7). Using the trial definition, major bleeding rates in patients treated with standard-dose clopidogrel ranged from 0.6% in COMMIT to 11.2% in PLATO. The contrast in bleeding rates of standard-dose clopidogrel among the trials was attenuated when using the thrombolysis in myocardial infarction (TIMI) definition for major bleeding (range 1.1-7.7%) and bleeding rates in all the trials were less than 2% when comparing 30 day rates of non-coronary artery bypass graft surgery-related TIMI major bleeding (range 0.3-1.9%). CONCLUSION: Differences in major bleeding rates between trials of P2Y(12) inhibitors in patients with ACS are minimized after standardization of bleeding definitions, timing of reporting of bleeding outcomes, and procedure rates. Interpretation of the risk of bleeding associated with different P2Y(12) inhibitors would be facilitated by a consistent approach to the definition and reporting of bleeding.

Cardiometabolic risk in Canada: a detailed analysis and position paper by the cardiometabolic risk working group.

The concepts of "cardiometabolic risk," "metabolic syndrome," and "risk stratification" overlap and relate to the atherogenic process and development of type 2 diabetes. There is confusion about what these terms mean and how they can best be used to improve our understanding of cardiovascular disease treatment and prevention. With the objectives of clarifying these concepts and presenting practical strategies to identify and reduce cardiovascular risk in multiethnic patient populations, the Cardiometabolic Working Group reviewed the evidence related to emerging cardiovascular risk factors and Canadian guideline recommendations in order to present a detailed analysis and consolidated approach to the identification and management of cardiometabolic risk. The concepts related to cardiometabolic risk, pathophysiology, and strategies for identification and management (including health behaviours, pharmacotherapy, and surgery) in the multiethnic Canadian population are presented. "Global cardiometabolic risk" is proposed as an umbrella term for a comprehensive list of existing and emerging factors that predict cardiovascular disease and/or type 2 diabetes. Health behaviour interventions (weight loss, physical activity, diet, smoking cessation) in people identified at high cardiometabolic risk are of critical importance given the emerging crisis of obesity and the consequent epidemic of type 2 diabetes. Vascular protective measures (health behaviours for all patients and pharmacotherapy in appropriate patients) are essential to reduce cardiometabolic risk, and there is growing consensus that a multidisciplinary approach is needed to adequately address cardiometabolic risk factors. Health care professionals must also consider risk factors related to ethnicity in order to appropriately evaluate everyone in their diverse patient populations.

Identification and management of cardiometabolic risk in Canada: a position paper by the cardiometabolic risk working group (executive summary).

With the objectives of clarifying the concepts related to "cardiometabolic risk," "metabolic syndrome" and "risk stratification" and presenting practical strategies to identify and reduce cardiovascular risk in multiethnic patient populations, the Cardiometabolic Working Group presents an executive summary of a detailed analysis and position paper that offers a comprehensive and consolidated approach to the identification and management of cardiometabolic risk. The above concepts overlap and relate to the atherogenic process and development of type 2 diabetes. However, there is confusion about what these terms mean and how they can best be used to improve our understanding of cardiovascular disease treatment and prevention. The concepts related to cardiometabolic risk, pathophysiology, and strategies for identification and management (including health behaviours, pharmacotherapy, and surgery) in the multiethnic Canadian population are presented. "Global cardiometabolic risk" is proposed as an umbrella term for a comprehensive list of existing and emerging factors that predict cardiovascular disease and/or type 2 diabetes. Health behaviour interventions (weight loss, physical activity, diet, smoking cessation) in people identified at high cardiometabolic risk are of critical importance given the emerging crisis of obesity and the consequent epidemic of type 2 diabetes. Vascular protective measures (health behaviours for all patients and pharmacotherapy in appropriate patients) are essential to reduce cardiometabolic risk, and there is growing consensus that a multidisciplinary approach is needed to adequately address cardiometabolic risk factors. Health care professionals must also consider ethnicity-related risk factors in order to appropriately evaluate all individuals in their diverse patient populations.

Understanding physicians' risk stratification of acute coronary syndromes: insights from the Canadian ACS 2 Registry.

BACKGROUND: An important treatment-risk paradox exists in the management of acute coronary syndromes (ACSs). However, the process of risk stratification by physicians and its relationship to the management of ACS have not been well studied. Our objective was to examine patient risk assessment by physicians in relation to treatment and objective risk score evaluation and the underlying patient characteristics that physicians consider to indicate high risk. METHODS: The prospective Canadian ACS 2 Registry recruited 1956 patients admitted for non-ST-segment elevation ACS in 36 hospitals in October 2002 to December 2003. We recorded patient risk assessment by the treating physician and case management on standardized case report forms and calculated the Thrombolysis in Myocardial Infarction (TIMI), Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT), and Global Registry of Acute Cardiac Events (GRACE) risk scores. RESULTS: Of the 1956 patients with ACS, 347 (17.8%) were classified as low risk, 822 (42.0%) as intermediate risk, and 787 (40.2%) as high risk by their treating physicians. Patients considered as high risk were more likely to receive aggressive medical therapies and to undergo coronary angiography and revascularization. However, there were only weak correlations between risk assessment by physicians and all 3 validated risk scores. In multivariable analysis, history of stroke, worse Killip class, presence of ST-segment deviation, T-wave inversion, and positive cardiac biomarker status were all independently associated with high-risk categorization by the treating physician, while advanced age and previous coronary bypass surgery were independent negative predictors. There was no significant association between the high-risk category and several established prognosticators, such as history of heart failure, hemodynamic variables, and creatinine level. CONCLUSIONS: Contemporary risk stratification of ACS appears suboptimal and may perpetuate the treatment-risk paradox. Physicians may not recognize and incorporate the most powerful adverse prognosticators into overall patient risk assessment. Routine use of validated risk score may enhance risk stratification and facilitate more appropriate tailoring of intensive therapies toward high-risk patients.

Bleeding and outcome in acute coronary syndrome: insights from continuous electrocardiogram monitoring in the Integrilin and Enoxaparin Randomized Assessment of Acute Coronary Syndrome Treatment (INTERACT) Trial.

BACKGROUND: Bleeding is associated with adverse outcome in acute coronary syndromes. However, the precise pathophysiologic mechanisms have not been elucidated. We sought to determine the relationship between bleeding and myocardial ischemia detected by concurrent continuous electrocardiogram (ECG) monitoring and their independent long-term prognostic significance. METHODS: The INTERACT trial was a randomized controlled trial of enoxaparin versus unfractionated heparin in patients with high-risk non-ST-elevation acute coronary syndromes. Continuous ECG monitoring, performed after enrollment up to 96 hours, was analyzed by an automated algorithm and reviewed by a blinded cardiologist. We centrally adjudicated all bleeding and clinical events in a blinded fashion and calculated the Global Registry of Acute Coronary Events risk score (a validated predictor of mortality) for each patient. RESULTS: Of the 746 patients enrolled, 34 (4.6%) developed major bleeding within 96 hours. After a median follow-up of 2.4 years, patients with bleeding had a higher risk of death (28.4% vs 7.3%, P < .001) and death/myocardial infarction (38.0% vs 12.9%, P < .001) compared with those without bleeding. Overall, 619 patients survived the first 96 hours with complete data on continuous ECG monitoring. Bleeding was associated with the simultaneous presence of ST-segment shifts on continuous ECG monitoring (P = .03). After adjusting for Global Registry of Acute Coronary Events risk score and myocardial ischemia detected by continuous ECG monitoring, major bleeding remained an independent predictor of death (adjusted hazard ratio = 3.48, 95% confidence interval 1.51-8.03, P = .003) and death/myocardial infarction (adjusted hazard ratio = 2.85, 95% confidence interval 1.40-5.78, P = .004). CONCLUSIONS: Bleeding is a powerful independent predictor of poor long-term outcome, even after adjusting for other associated prognostic factors such as advanced age and renal dysfunction. Although bleeding is associated with concurrent myocardial ischemia, its adverse prognostic impact may be mediated by complex pathophysiologic mechanisms rather than myocardial ischemia alone. Our findings suggest that future investigations should focus on other biologically plausible mechanisms.

Optimal medical therapy at discharge in patients with acute coronary syndromes: temporal changes, characteristics, and 1-year outcome.

BACKGROUND: There are limited data on the recent trend in the use of optimal evidence-based medical therapies after acute coronary syndromes (ACSs). We sought to evaluate (1) the temporal changes in medical management of patients discharged after an ACS; (2) patient and practice characteristics associated with optimal medical therapy at discharge; and (3) the association between discharge medication use and 1-year outcome. METHODS: The Canadian ACS I (September 1999-June 2001) and ACS II (October 2002-December 2003) Registries were prospective, multicenter, observational studies of 6853 patients admitted for ACS. We examined the discharge use of medications among 5833 hospital survivors who did not have any contraindications to antiplatelet/anticoagulant, beta-blocker, angiotensin-converting enzyme inhibitor, or lipid-modifying therapies. Optimal medical therapy was defined as the use of all indicated medications. Follow-up data at 1 year were collected by telephone interview. We performed hierarchical logistic regression to identify patient characteristics and care patterns associated with optimal medical treatment and to examine its relationship with 1-year mortality. RESULTS: There were significant increases in the discharge use of all 4 classes of medications over time; 28.9% and 51.8% of patients in ACS I and ACS II Registries, respectively, were prescribed optimal medical therapy (P < .001). Advanced age, female sex, prior heart failure, renal dysfunction, and coronary bypass surgery during hospitalization were negative independent predictors of optimal medical therapy. Conversely, enrollment in ACS II Registry, history of dyslipidemia, presence of ST elevation and abnormal cardiac biomarker, previous myocardial infarction, and previous coronary revascularization were independently associated with the use of combination therapy. After adjusting for other validated prognosticators, patients receiving optimal medical therapy had significantly lower 1-year mortality (adjusted odds ratio 0.54, 95% confidence interval 0.36-0.81, P = .003) compared with those given 0 or 1 drug at discharge. Over the 1-year follow-up period, substantial numbers of patients discontinued therapies, whereas others were initiated on treatment. CONCLUSIONS: Despite the temporal increases in the combined use of evidence-based pharmacologic therapies, which is associated with improved outcome, medical management of ACS remains suboptimal. Quality improvement strategies are needed to enhance the appropriate use of effective therapies, targeting specifically the high-risk but undertreated patients who may derive the greatest therapeutic benefit.

Contemporary management of dyslipidemia in high-risk patients: targets still not met.

PURPOSE: Our objective was to evaluate treatment patterns and the attainment of current National Cholesterol Education Program (NCEP)-recommended lipid targets in unselected high-risk ambulatory patients. METHODS: Between December 2001 and December 2004, the prospective Vascular Protection and Guidelines Oriented Approach to Lipid Lowering Registries recruited 8056 outpatients with diabetes, established cardiovascular disease (CVD), or both, who had a complete lipid profile measured within 6 months before enrollment. The primary outcome measure was treatment success, defined as the achievement of LDL-cholesterol<2.6 mmol/L (100 mg/dL) according to NCEP guidelines. We examined patient characteristics and use of lipid-modifying therapy in relation to treatment outcome, which included the recently proposed optional LDL-cholesterol target (<1.8 mmol/L [70 mg/dL]) for very high-risk patients. RESULTS: Overall, 78.2% of patients were treated with a statin and 51.2% had achieved the recommended LDL-cholesterol target. Treatment success rate was highest in diabetic patients with CVD (59.6%), followed by nondiabetic patients with CVD (51.8%), and lowest (44.8%) in diabetic patients without CVD (P<.0001). Compared with untreated patients, those on statins were more likely to achieve target (34.4% vs 55.9%, P<.0001). Of the patients who failed to meet target, only 9.9% were taking high-dose statin, while 29.3% were not prescribed any statin therapy. Among very high-risk patients, 20.8% attained the optional LDL-cholesterol goal. In multivariable analysis, advanced age, male sex, diabetes, coronary artery disease, coronary revascularization, and use of statin were associated with treatment success (all P<.0001). CONCLUSION: Despite the well-established benefits of available lipid-modifying drugs, current management of dyslipidemia continues to be suboptimal, with a substantial proportion of patients failing to achieve guideline-recommended lipid targets. There remains an important opportunity to improve the quality of care for these high-risk patients.

Randomized evaluation of the efficacy of enoxaparin versus unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes receiving the glycoprotein IIb/IIIa inhibitor eptifibatide. Long-term results of the Integrilin and Enoxaparin Randomized Assessment of Acute Coronary Syndrome Treatment (INTERACT) trial.

BACKGROUND: Patients with high-risk non-ST-segment elevation acute coronary syndromes (NSTE ACS) benefit from the early administration of aspirin, a small molecule glycoprotein IIb/IIIa inhibitor such as eptifibatide, and heparin. The INTERACT trial demonstrated that in high-risk patients with ACS receiving aspirin and eptifibatide, the use of enoxaparin compared with unfractionated heparin (UFH) was associated with less bleeding, less early myocardial ischemia, and improved 30-day outcomes. OBJECTIVE: The aim of our study was to determine whether the short-term benefits of enoxaparin compared with UFH observed in high-risk patients with NSTE ACS are maintained over a prolonged period of follow-up. METHODS: Six hundred thirty-nine patients that were representative of the total population of subjects in the INTERACT trial were followed up for a median period of 2.5 years. RESULTS: In this group, the early benefit of enoxaparin was maintained. The incidence of death or myocardial infarction at the time of long-term follow-up was 39% lower in patients receiving enoxaparin compared with those who received UFH (8.9% vs 14.7%, P = .024). There was no difference in the frequency of cardiac catheterization in the groups receiving either enoxaparin or UFH. CONCLUSIONS: The early treatment of high-risk patients with NSTE ACS receiving aspirin and eptifibatide with enoxaparin is associated with early outcome benefits that are sustained over a prolonged follow-up period. This trial supports the concept that early treatment directed against platelet and thrombin formation is associated with better short- and long-term outcomes.