Abstract Background We examined whether the efficacy of an early invasive strategy after fibrinolysis in ST-segment elevation myocardial infarction (STEMI) differs in relation to the initial troponin ...status. Methods In the T rial of R outine A ngioplasty and S tenting After F ibrinolysis to E nhance R eperfusion in A cute M yocardial I nfarction (TRANSFER-AMI), patients with STEMI presenting to a non-percutaneous coronary intervention (PCI)-capable hospital who received fibrinolysis were randomized to either a pharmacoinvasive or standard strategy for subsequent angiography and PCI. In this post hoc subgroup analysis, we compared the efficacy of these strategies in relation to the initial troponin status at hospital presentation for the primary composite end point of mortality, reinfarction, recurrent ischemia, heart failure, and cardiogenic shock at 30 days. We assessed the heterogeneity of treatment effect with initial troponin status using the Breslow-Day test and tested for interaction after adjustment for baseline Global Registry of Acute Coronary Events (GRACE) risk score. Results Among 1059 patients, those with abnormal initial troponin levels (n = 514 48.5%) were older with worse Killip class, had a longer time from symptom onset to fibrinolysis, and had higher GRACE and Thrombolysis In Myocardial Infarction risk scores. Patients with abnormal troponin levels had higher rates of the primary end point (17.5% vs 10.8%; P = 0.002) and cumulative mortality or reinfarction at 1 year (14.0% vs 8.1%; P = 0.003). In stratified analyses, pharmacoinvasive management reduced the primary end point only among patients with normal initial troponin status. However, there was no significant treatment heterogeneity (all P ≥ 0.10) and no interaction between initial troponin status and treatment assignment after adjusting for GRACE risk score. Conclusions Patients with STEMI and abnormal initial troponin levels had worse short-term and long-term outcomes. Accounting for overall baseline risk with the GRACE risk score, troponin status did not modulate the efficacy of pharmacoinvasive management.
Randomized controlled trials support the use of an early invasive strategy in high-risk patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS). Although risk increases with age, ...limited data are available to support this strategy in older patients. The aims of this study were to examine temporal trends in the management and outcomes of NSTE ACS in elderly patients and to explore reasons for the lower use of early angiography in the aged population. Data from 11,732 patients with NSTE ACS were collected from 3 consecutive Canadian registries (ACS I, ACS II, and Global Registry of Acute Coronary Events GRACE/GRACE2 ) from 1999 to 2007. Rates of in-hospital cardiac catheterization, revascularization, infarction or reinfarction, and death were stratified by age (<65, 65 to 74, and ≥75 years). Although overall, rates of in-hospital catheterization and revascularization increased over time (p <0.001), the largest increase occurred in patients aged <65 years. The strongest independent negative predictor of the use of cardiac catheterization was age ≥75 years (adjusted odds ratio 0.45, 95% confidence interval 0.37 to 0.56, p <0.001). Use of an early invasive approach was associated with a reduction in 1-year mortality across all age groups, but the absolute difference was greatest in patients aged ≥75 years. The underestimation of risk by physicians (ascertained in ACS II) was the most common reason for choosing a conservative strategy. In conclusion, despite an overall increased use of an early invasive strategy, elderly patients with NSTE ACS remain significantly less likely to undergo cardiac catheterization and revascularization and are often erroneously perceived to be at low risk by their physicians. Future studies should determine whether more aggressive treatment of these high-risk elderly patients improves outcomes.
Compared with non-smokers, cigarette smokers with ST-segment elevation myocardial infarctions derive greater benefit from fibrinolytic therapy. However, it is not known whether the optimal treatment ...strategy after fibrinolysis differs on the basis of smoking status. The Trial of Routine Angioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) randomized patients with ST-segment elevation myocardial infarctions to a routine early invasive (pharmacoinvasive) versus a standard (early transfer only for rescue percutaneous coronary intervention or delayed angiography) strategy after fibrinolysis. The efficacy of these strategies was compared in 1,051 patients on the basis of their smoking status. Treatment heterogeneity was assessed between smokers and non-smokers, and multivariable analysis was performed to evaluate for an interaction between smoking status and treatment strategy after adjusting for baseline Global Registry of Acute Coronary Events (GRACE) risk score. Smokers (n = 448) were younger, had fewer cardiovascular risk factors, and had lower GRACE risk scores. They had a lower rate of the primary composite end point of 30-day mortality, reinfarction, recurrent ischemia, heart failure, or cardiogenic shock and fewer deaths or reinfarctions at 6 months and 1 year. Smoking status was not a significant predictor of either primary or secondary end points in multivariable analysis. Pharmacoinvasive management reduced the primary end point compared with standard therapy in smokers (7.7% vs 13.6%, p = 0.04) and non-smokers (13.1% vs 19.7%, p = 0.03). Smoking status did not modify treatment effect on any measured outcomes (p >0.10 for all). In conclusion, compared with non-smokers, current smokers receiving either standard or early invasive management of ST-segment elevation myocardial infarction after fibrinolysis have more favorable outcomes, which is likely attributable to their better baseline risk profile. The beneficial treatment effect of a pharmacoinvasive strategy is consistent in smokers and non-smokers.
Background Concomitant use of proton-pump inhibitors (PPIs) has been implicated in diminished antiplatelet response to clopidogrel and an increased risk of ischemic events, but primarily among ...patients undergoing percutaneous coronary intervention. We sought to examine the potential influence of interactions between PPIs and clopidogrel versus prasugrel on platelet reactivity and clinical outcomes after acute coronary syndromes (ACS) in patients managed medically without revascularization. Methods This analysis from the TRILOGY ACS trial focused upon the 7,243 ACS patients aged <75 years who were managed without revascularization, randomized to clopidogrel or prasugrel, and followed for a median of 17 months. Proton-pump inhibitor type and use were assessed at each study visit, and 2,049 of the patients in this cohort underwent serial platelet reactivity assessments. Results Proton-pump inhibitor use (23%) was similar between the clopidogrel and prasugrel groups at baseline and throughout the study. Median on-treatment platelet reactivity values were consistently lower with prasugrel versus clopidogrel irrespective of PPI use. For the primary end point (composite of cardiovascular death, myocardial infarction MI, or stroke), PPI use modified the unadjusted treatment effect of prasugrel versus clopidogrel (interaction P = .02). After adjusting for differences in baseline characteristics, this treatment effect modification was attenuated for the composite end point (interaction P = .06) but was significant for the MI component end point (interaction P = .01). Similarly, among patients on a PPI, the frequency of MI was significantly lower with prasugrel versus clopidogrel (hazard ratio = 0.61; 95% CI 0.42-0.88). These findings were similar by PPI type (omeprazole and pantoprazole). Conclusions Among ACS patients managed without revascularization, use of PPIs did not result in a differential antiplatelet response between prasugrel versus clopidogrel but was associated with a lower incidence of MI with prasugrel. These hypothesis-generating findings suggest that factors besides platelet reactivity may underlie the differential risk of MI observed by treatment assignment with PPI use.
Previous studies have questioned the external validity of randomized controlled trial results of acute coronary syndrome (ACS) because of potential selection bias toward healthier patients. We sought ...to evaluate differences in clinical characteristics and management of patients admitted with non–ST-elevation ACS according to participation in clinical trials over the previous decade. The Canadian ACS I (1999 to 2001), ACS II (2002-2003), GRACE (2004-2007), and CANRACE (2008) were prospective, multicenter registries of patients admitted to hospitals with ACS. We examined 13,556 patients with non–ST-elevation ACS, of whom 1,126 (8.3%) participated in clinical trials. Data were collected on baseline characteristics, medication use at admission and discharge, in-hospital procedures, and in-hospital adverse events. Patients enrolled in clinical trials were younger, more likely to be men, and had fewer co-morbidities. They were significantly more likely to be on several guideline-recommended medications and were significantly more likely to undergo invasive procedures, including coronary angiography, percutaneous coronary intervention, and coronary bypass surgery (all p values <0.001). Unadjusted in-hospital (2.1% vs 0.7%, p = 0.001) and 1-year (8.9% vs 6.3%, p = 0.037) mortality rates were higher in non-enrolled patients. In multivariable analysis, patients who were older, women, had a history of heart failure, and increased creatinine levels on presentation were less likely to be enrolled into clinical trials. In conclusion, significant differences persist in baseline characteristics, treatment, and outcomes between patients enrolled and those not enrolled in clinical trials. Consequently, generalization of ACS clinical trials over the previous decade to the “real-world” patient may remain in question.
The aim of this study was to assess the efficacy and safety of an early invasive strategy post-fibrinolysis in relation to time from symptom onset to fibrinolysis in patients with ST-elevation ...myocardial infarction (STEMI). The Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) randomized 1,059 patients receiving fibrinolysis for STEMI to an early invasive strategy versus standard therapy. The primary end point was the composite of death, reinfarction, recurrent ischemia, new or worsening heart failure, or cardiogenic shock at 30 days. In this post hoc subgroup analysis, we examined the effect of an early invasive strategy on efficacy and safety outcomes after stratification by time from symptom onset to fibrinolysis (<2 or ≥2 hours). Of 1,059 patients in TRANSFER-AMI, 557 (53%) received fibrinolysis <2 hours and 502 (47%) ≥2 hours after symptom onset. Compared to patients who received fibrinolysis within 2 hours of symptoms, patients who received fibrinolysis ≥2 hours after symptom onset had higher Global Registry of Acute Coronary Events risk scores (median 127 vs 122, p = 0.004). The effect of an early invasive strategy did not differ between symptom-to-fibrinolysis time strata for the primary efficacy end point (p-heterogeneity = 0.67), 30-day mortality, the composite of death or reinfarction at 30 days, 6 months, or 1 year, or bleeding (all p-heterogeneity >0.40). In conclusion, the efficacy and safety of an early invasive strategy in patients undergoing fibrinolysis for STEMI do not vary in relation to time (<2 or ≥2 hours) from symptom onset to fibrinolysis.
Background ST-segment depression (STD) is predictive of adverse outcomes in non–ST-segment elevation acute coronary syndromes (NSTE-ACS), but there are conflicting data on the incremental prognostic ...value of T-wave inversions (TWIs) on the admission electrocardiogram. Methods Admission electrocardiograms of 7,343 patients with NSTE-ACS from the Global Registry of Acute Coronary Events (GRACE) and ACS I registry were independently analyzed at a core laboratory and stratified by TWI and STD status. We performed multivariable analyses to determine the independent prognostic significance of TWI and tested for interaction between TWI and STD for adverse outcomes. Results Patients with TWI and/or STD had a higher prevalence of cardiovascular risk factors, higher Killip class, and higher GRACE risk scores. Among the 2,708 patients with available angiographic data, rates of 3-vessel or left main disease were similar between patients with TWI and those without TWI/STD. After adjusting for other established prognosticators, TWI did not independently predict in-hospital (adjusted odds ratio 1.03, 95% CI 0.75-1.42, P = .85) or 6-month mortality (adjusted odds ratio 1.02, 95% CI 0.80-1.30, P = .88); STD remained a strong independent predictor. There was no interaction between TWI and STD for these outcomes. No contiguous lead groups or cumulative number of leads with TWI provided independent prognostic information. Conclusions TWI is associated with other high-risk clinical features but is not an independent predictor of adverse short- and long-term mortality in NSTE-ACS. T-wave inversion does not provide additional prognostication beyond the GRACE risk model, and its concomitant presence does not alter the prognostic value of STD.
Obesity is associated with hypertension, dyslipidemia, and diabetes, but it is also an independent cardiovascular risk factor. We sought to evaluate the differences in treatment patterns and ...attainment of guideline-recommended targets among high-risk vascular outpatients in relation to their body mass index (BMI). The prospective Vascular Protection and Guideline Orientated Approach to Lipid Lowering Registries recruited 7,357 high-risk vascular outpatients in Canada from 2001 to 2004. We stratified the patient population into 3 groups according to their BMI: normal weight (BMI <24.9 kg/m2 ), overweight (BMI 25 to 29.9 kg/m2 ), and obese (BMI >30 kg/m2 ). We evaluated the rates of attainment for contemporary guideline targets of blood pressure (<140/90 or <130/80 mm Hg in the presence of diabetes) and lipids (low-density lipoprotein LDL <2.5 mmol/L 96.7 mg/dl and total cholesterol TC/high-density lipoprotein HDL ratio <4.0). Of the 7,357 patients, 1,305 (17.7%) were normal weight, 2,791 (37.9%) overweight, and 3,261 (44.4%) obese, as determined by the BMI. Obese patients were younger and more likely to have hypertension and diabetes (all p <0.001 for trend). Obese patients had higher baseline blood pressure, TC, LDL cholesterol, triglyceride levels and TC/HDL ratio, and lower HDL cholesterol. Obese patients were more likely to be treated with antihypertensive agents (p = 0.002), angiotensin-converting enzyme inhibitors (p = 0.024), angiotensin receptor blockers (p <0.001), and high-dose statin therapy (p = 0.001). On multivariable analyses, obese patients were less likely to attain the blood pressure (odds ratio 0.77, 95% confidence interval 0.66 to 0.90, p = 0.001) and TC/HDL ratio (odds ratio 0.48, 95% confidence interval 0.42 to 0.55, p <0.001) targets but not the LDL targets (odds ratio 0.89, 95% confidence interval 0.78 to 1.03, p = 0.11). In conclusion, only a minority ambulatory patients at high cardiovascular risk achieved both guideline-recommended blood pressure and lipid targets, and this significant treatment gap was more pronounced among obese patients. Our findings underscore the opportunity to optimize the treatment of these high-risk patients.
In patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), selecting an antithrombotic regimen requires balancing risks of ischemic cardiac events, stroke, and ...bleeding.
We studied 467 patients with AF undergoing PCI in the time period from December 2015 to July 2018 identified via a chart audit by 47 Canadian cardiologists in the CONNECT AF+PCI (the Coordinated National Network to Engage Interventional Cardiologists in the Antithrombotic Treatment of Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) study, to determine patterns of initial antithrombotic therapy selection.
The median (25th, 75th percentile) CHADS2 score was 2 (1, 3), and PCI was performed in the setting of acute coronary syndrome in 62.1%. Triple antithrombotic therapy (TAT) was the initial treatment in 62.7%, dual-pathway therapy in 25.7%, and dual antiplatelet therapy in 11.6%, with a temporal increase in use of dual-pathway therapy during the course of the study; median intended TAT duration was 1 (1, 3) month. Compared with patients selected for TAT, patients selected for dual-pathway therapy were less likely to have prior myocardial infarction (35.8% vs 25.8%, P = 0.045) and prior PCI (33.8% vs 23.3%, P = 0.03), and they received shorter total length of stents (38 23, 56 vs 30 20, 46 mm, P = 0.03). Patients selected for dual-pathway therapy had a higher prevalence of prior stroke/transient ischemic attack (13.0% vs 23.3%, P = 0.01). There was no difference in prevalence of anemia (21.5% vs 25.8%, P = 0.30). Use of dual-pathway therapy was similar among patients with acute coronary syndrome and those with stable disease (24.1% vs 28.2%, P = 0.32).
Approximately one-quarter of AF patients undergoing PCI are treated with dual-pathway therapy in Canadian practice, with its use increasing during the studied period. Patients selected for dual-pathway therapy have less-complex coronary disease history and intervention.
Les patients atteints de fibrillation auriculaire (FA) qui subissent une intervention coronarienne percutanée (ICP) et choisissent un schéma posologique antithrombotique ont besoin de peser les risques d’événements cardiaques d’origine ischémique, d’accidents vasculaires cérébraux et d’hémorragies.
Les 467 patients atteints de FA ayant subi une ICP de décembre 2015 à juillet 2018 qui ont fait l’objet de notre étude ont été trouvés lors de la vérification des dossiers par 47 cardiologues canadiens de l’étude CONNECT AF+PCI (CoordinatedNationalNetwork toEngage InterventionalCardiologists in the AntithromboticTreatment of Patients WithAtrialFibrillation UndergoingPercutaneousCoronaryIntervention) pour déterminer les schémas de sélection du traitement antithrombotique initial.
Le score CHADS2 médian (25e, 75e percentile) était de 2 (1, 3), et l’ICP avait été réalisée dans le cadre du syndrome coronarien aigu chez 62,1 % des patients. La trithérapie antithrombotique (TTA) était le traitement initial chez 62,7 % des patients, la bithérapie, chez 25,7 % des patients, et la bithérapie antiplaquettaire, chez 11,6 % des patients, mais il y avait une augmentation temporelle dans l’utilisation de la bithérapie durant l’étude; la durée médiane prévue de la TTA était de 1 (1, 3) mois. Comparativement aux patients sélectionnés pour la TTA, les patients sélectionnés pour la bithérapie étaient moins susceptibles d’avoir eu un infarctus du myocarde précédent (35,8 % vs 25,8 %, P = 0,045) et une ICP précédente (33,8 % vs 23,3 %, P = 0,03), et recevaient des endoprothèses de longueur totale plus courte (38 23, 56 vs 30 20, 46 mm, P = 0,03). Les patients sélectionnés pour la bithérapie montraient une prévalence plus élevée d’accidents vasculaires cérébraux/accidents ischémiques transitoires (13,0 % vs 23,3 %, P = 0,01). Il n’existait aucune différence dans la prévalence de l’anémie (21,5 % vs 25,8 %, P = 0,30). L’utilisation de la bithérapie était similaire chez les patients atteints d’un syndrome coronarien aigu et chez les patients dont la maladie était stable (24,1 % vs 28,2 %, P = 0,32).
Dans la pratique canadienne, environ le quart des patients atteints de FA qui subissent une ICP sont traités par bithérapie, mais durant la période étudiée, son utilisation avait augmenté. Les patients sélectionnés pour la bithérapie ont des antécédents et des interventions liées aux maladies coronariennes moins complexes.
Background Hypertension is a well-established risk factor for cardiovascular disease, whereas low systolic blood pressure (SBP) is a powerful adverse prognosticator in acute coronary syndrome. ...However, it is unclear whether the prognostic significance of low SBP differs in patients with versus without prior history of hypertension. We sought to investigate the relationships between presenting SBP, prior hypertension, antihypertensive medication use, and outcomes in non–ST-segment elevation acute coronary syndrome (NSTEACS). Methods Using data from GRACE/GRACE2 and CANRACE, we stratified 10,337 patients with NSTEACS from 1999 to 2008 into 2 groups: those with and those without prior diagnosis of hypertension. We performed multivariable logistic regression analysis to assess the prognostic significance of prior hypertension on in-hospital mortality and tested for the interactions between prior hypertension, antihypertensive medication use, and presenting SBP. Results Compared with patients without prior hypertension (n = 3,732), those with prior hypertension (n = 6,605) were older; more likely to be female; and more frequently had diabetes, previous myocardial infarction, heart failure, renal insufficiency, and higher Killip class and GRACE risk scores on presentation. Patients with prior hypertension were more likely to be on antihypertensive medications before admission, to present with higher SBP, and to have heart failure or cardiogenic shock in hospital (6.0% vs 10.1%; P < .001). In-hospital mortality was higher among patients presenting with lower SBP but did not differ between the groups with and without prior hypertension. In multivariable analysis, neither prior hypertension (adjusted odds ratio = 1.15, 95% CI 0.78-1.70, P = .48) nor the number of antihypertensive medications used ( P for trend = .84) was independently associated with in-hospital mortality. In contrast, SBP was a strong independent predictor of in-hospital mortality (adjusted odds ratio = 1.21 per 10 mm Hg lower, 1.15-1.27, P < .001). There was no significant interaction between SBP and prior hypertension ( P for interaction = .62) or pre-admission antihypertensive medication use ( P for interaction = .46) with respect to in-hospital mortality. Conclusion Low SBP on presentation, but not prior hypertension, was independently associated with in-hospital mortality in NSTEACS. The powerful prognostic value of SBP is similar regardless of a history of hypertension or pre-admission antihypertensive medication use.
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