Abstract 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.
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 GRACE2 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.
...despite the higher rates of major bleeding seen among patients with history of bleeding, there were no significant differences in the relative efficacy (stroke/systemic embolism, death) or safety ...(hemorrhagic stroke, major bleeding) of the NOAC apixaban compared with warfarin.16 The observation that previous hemorrhage portends a higher risk for subsequent bleeding16 among patients on an NOAC or a VKA is consistent with previous findings reported by the ARISTOTLE researchers,22,23 and our determination from the Rivaroxaban Once-daily oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial24 that prior gastrointestinal (GI) bleeding was an independent predictor of future major bleeding.25 Gastrointestinal bleeding is the most common site of major hemorrhage with OAC, and there appears to be a higher propensity to GI bleeding with some (eg, dabigatran 150 mg twice daily,26 rivaroxaban,25,27 edoxaban 60 mg once daily28) but not other (eg, dabigatran 110 mg twice daily,26 apixaban 5 mg twice daily,22 edoxaban 30 mg once daily28) NOAC drugs/doses compared with VKA treatment.
Abstract Background Limited longitudinal data are available on attainment of guideline-recommended treatment targets among ambulatory patients at high risk for cardiovascular events. Methods The ...Vascular Protection registry and the Guidelines Oriented Approach to Lipid Lowering registry recruited 8056 ambulatory patients at high risk for, or with established cardiovascular disease; follow-up was not protocol-mandated. We stratified the study population according to the availability of 6-month follow-up data into 2 groups, and compared their clinical characteristics, medication profile, and attainment of contemporaneous guideline-recommended blood pressure (BP) and lipid targets both at enrollment and at 6-month follow-up. Results Of the 8056 patients, only 5371 (66.7%) patients had 6-month follow-up, who had significant increases in the use of statins and antihypertensive medications at 6 months compared with at enrollment (all P < 0.001). Compared with at time of enrollment, more patients attained the BP target (45.3% vs 42.3%), low-density lipoprotein cholesterol (LDL-C) target (62.8% vs 45.8%), and both targets (29.7% vs 21.6%) at 6-month follow-up (all P < 0.001). In multivariable analysis, independent predictors of attainment of BP target included history of coronary artery disease and heart failure (all P ≤ 0.001). On the other hand, advanced age, diabetes, coronary artery disease, previous coronary revascularization, and use of statin therapy were independently associated with achievement of LDL-C target (all P < 0.005). Conclusions Most (> 50%) patients without 6-month follow-up did not attain guideline-recommended BP and LDL-C targets at enrollment. Although BP and lipid control improved at 6 months among patients with follow-up, most still failed to achieve optimal BP and lipid targets. Effective ongoing quality improvement measures and follow-up are warranted.
Abstract Background Patients with acute coronary syndrome (ACS), especially those receiving medical management without revascularization, are at high risk for spontaneous myocardial infarction (MI), ...but its frequency and predictors are unknown. Objectives This study sought to characterize spontaneous MI events in a randomized population during 30 months of follow-up and develop a prediction model for spontaneous MI to assign risk of spontaneous MI events in ACS populations. Methods We analyzed data from the randomized TRILOGY ACS (TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medically manage Acute Coronary Syndromes) trial of aspirin plus prasugrel or clopidogrel following ACS. The trial included 9,326 patients with non–ST-segment elevation myocardial infarction (NSTEMI)/unstable angina (UA) who were managed medically without planned revascularization. Our study population included 9,294 patients. A multivariable Cox proportional hazards model was developed to determine predictors of time to first spontaneous MI event through 30 months. After model validation, we developed a calculator for model implementation. Results Among 9,294 patients, 695 spontaneous MI events occurred over a median of 17 months, representing 94% of adjudicated MI events (n = 737). The Kaplan-Meier event rate of spontaneous MI through 30 months was 10.7%. The strongest predictors of spontaneous MI were older age, NSTEMI versus UA as index event, diabetes mellitus, no pre-randomization angiography, and higher baseline creatinine values. The model exhibited good predictive capabilities ( c -index = 0.732) and had good calibration, especially for patients with low-to-moderate risk of spontaneous MI. Conclusions Spontaneous MI following a medically managed UA/NSTEMI event is common. Baseline characteristics can be used to predict subsequent risk of spontaneous MI in this population. These findings provide insight into the long-term natural history of medically managed UA/NSTEMI patients and could be used to optimize risk stratification and treatment of these patients. (A Comparison of Prasugrel and Clopidogrel in Acute Coronary Syndrome Subjects TRILOGY ACS; NCT00699998 )
The objectives of this national chart audit (January to June 2013) of 6,346 patients with atrial fibrillation (AF; ≥18 years without a significant heart valve disorder) from 647 primary care ...physicians were to (1) describe the frequency of stroke and bleed risk assessments in patients with nonvalvular AF by primary care physicians, including the accuracy of these assessments relative to established predictive indexes; (2) outline contemporary methods of anticoagulation used; and (3) report the time in the therapeutic range among patients prescribed warfarin. An annual stroke risk assessment was not undertaken in 15% and estimated without a formal risk tool in 33%; agreement with CHADS2 score estimation was seen in 87% of patients. Major bleeding risk assessment was not undertaken in 25% and estimated without a formal risk tool in 47%; agreement with HAS-BLED score estimation was observed in 64% with physician overestimation in 26% of patients. Antithrombotic therapy included warfarin (58%), dabigatran (22%), rivaroxaban (14%), and apixaban (<1%). Among warfarin-treated patients, the median international normalized ratio was 2.4 and time in therapeutic range (TTR) was 73%; however, the TTR was <50% in 845 (25%), 50% to 69% in 674 (20%), and ≥70% in 1,827 (55%) patients. In conclusion, we describe a contemporary real-world elderly population with AF at important risk for stroke. There is apparent overestimation of bleeding risk in many patients. Warfarin was the dominant stroke prevention treatment; however, the suggested TTR target was achieved in only 55% of these patients.
Primary percutaneous coronary intervention (PCI) is the treatment of choice for patients presenting with acute ST-segment elevation myocardial infarction (STEMI). However, if catheterization ...facilities are not immediately available, the effectiveness of PCI can be affected by delays in transfer. Evidence suggests that antiplatelet therapy administered early, preferably in the ambulance during transfer, may provide better and earlier perfusion. Ticagrelor, a direct platelet P2Y12 receptor inhibitor, is indicated for the management of patients with acute coronary syndromes. The ATLANTIC study ( NCT01347580 ; EudraCT 2011-000214-19) is a 30-day international, randomized, parallel-group, placebo-controlled study in male and female patients (aged ≥18 years) who are diagnosed as having STEMI, with intended primary PCI. In total, 1770 patients will be randomized immediately after diagnosis to prehospital administration of ticagrelor 180 mg followed by matching placebo administered in hospital, or prehospital administration of placebo followed by ticagrelor 180 mg administered in hospital. All patients will then receive ticagrelor 90 mg twice daily for 30 days. The coprimary end point is the percentage of patients reaching thrombolysis in myocardial infarction flow grade 3 in the infarct-related artery at initial angiography or achieving ≥70% ST-segment elevation resolution pre-PCI. The primary safety end point is major, life-threatening, or minor bleeding after ticagrelor administration. The results of this study may have an impact on future recommendations for treatment for patients with STEMI.
Background There are limited contemporary data on the early use of clopidogrel or glycoprotein (Gp) IIb/IIIa inhibitors, alone versus combination therapies, in non–ST-elevation acute coronary ...syndrome (NSTE-ACS). Methods This study included 5,806 Canadian NSTE-ACS patients with elevated cardiac biomarker and/or ST deviation on presentation in the prospective GRACE between 2003-2007. We stratified the study population according to the management strategy (non-invasive vs invasive) and into low-(GRACE risk score ≤108), intermediate- (109-140), and high-risk groups (≥141). Results Overall, 3,893 patients (67.1%) received early (≤24 hours of admission) antiplatelet therapy; the rates of use were 76%, 73%, and 57% in the low-, intermediate-, and high-risk groups, respectively ( P for trend < .001). Only 54% of the conservatively managed patients and 12% of the invasively managed patients received early clopidogrel and GpIIb/IIIa inhibitors, respectively. High-risk patients were less likely (adjusted odds ratio = 0.48, 95% CI 0.39-0.59, P < .001) to receive early clopidogrel or GpIIb/IIIa inhibitors, whereas in-hospital catheterization was an independent positive predictor (adjusted odds ratio = 2.02, 95% CI 1.74-2.34, P < .001) of use. Conclusions In this contemporary NSTE-ACS population, both clopidogrel and GpIIb/IIIa inhibitors were targeted toward patients treated with an invasive strategy but paradoxically toward the lower-risk group. In particular, clopidogrel appeared to be underused among conservatively managed patients despite its proven efficacy, whereas GpIIb/IIIa inhibitors were administered to only a minority of the high-risk patients with elevated cardiac biomarkers. Our findings emphasize the ongoing need to promote the optimal use of evidence-based antiplatelet therapies among high-risk patients with NSTE-ACS.
Background Habitual smoking has been associated with increased platelet reactivity, increased risk of thrombotic complications and greater efficacy of clopidogrel therapy over placebo. In the PLATO ...trial, ticagrelor compared to clopidogrel in patients with acute coronary syndromes (ACS) reduced the primary composite end point of vascular death, myocardial infarction and stroke, without increasing overall rates of major bleeding. We evaluated the results in relation to smoking habits. Methods Interactions between habitual smokers (n = 6678) and in ex/nonsmokers (n = 11,932) and the effects of randomized treatments on ischemic and bleeding outcomes were evaluated by Cox regression analyses. Results Habitual smokers had an overall lower risk profile and more often ST-elevation ACS. After adjustment for baseline imbalances, habitual smoking was associated with a higher incidence of definite stent thrombosis (adjusted HR, 1.44 95% CI, 1.07-1.94); there were no significant associations with other ischemic or bleeding end points. The effects of ticagrelor compared to clopidogrel were consistent for all outcomes regardless of smoking status. Thus, there was a similar reduction in the primary composite end point for habitual smokers (adjusted HR, 0.83 95% CI, 0.68-1.00) and ex/nonsmokers (adjusted HR, 0.89 95% CI, 0.79-1.00) (interaction P = .50), and in definite stent thrombosis for habitual smokers (adjusted HR, 0.59 0.39-0.91) and ex/nonsmokers (adjusted HR, 0.69 95% CI, 0.45-1.07) (interaction P = .61). Conclusions In patients hospitalized with ACS, habitual smoking is associated with a greater risk of subsequent stent thrombosis. The reduction of vascular death, myocardial infarction, stroke, and stent thrombosis by ticagrelor compared to clopidogrel is consistent regardless of smoking habits.
Despite clinical trial evidence supporting the use of antiplatelets, angiotensin-converting enzyme inhibitors, and statins for cardiovascular risk reduction in high-risk patients, use of such ...therapies in real-world outpatients in the prospective Vascular Protection Registry and the Guidelines Oriented Approach to Lipid Lowering Registry was suboptimal (78%, 55%, and 75%, respectively). The most frequent reason physicians cited for nonprescription of statins (33%) was that patients were not high risk enough and/or current guidelines did not support statin use. In conclusion, outpatients at high cardiovascular risk continue to be undertreated as a result of a combination of physician underestimation of cardiovascular risk (knowledge gap) and barriers to implementation of evidence-based therapy (practice gap).
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