Use and outcomes of dual antiplatelet therapy for acute coronary syndrome in patients with chronic kidney disease: insights from the Canadian Observational Antiplatelet Study (COAPT).

Chronic kidney disease (CKD) increases the risk of adverse outcomes in acute coronary syndrome (ACS). The optimal regimen of dual antiplatelet therapy (DAPT) post-percutaneous coronary intervention (PCI) in CKD poses a challenge due to the increased bleeding and clotting tendencies, particularly since patients with CKD were underrepresented in randomized controlled trials. We examined the practice patterns of DAPT prescription stratified by the presence of CKD. The multicentre prospective Canadian Observational Antiplatelet Study (COAPT) enrolled patients with ACS between December 2011 and May 2013. The present study is a subgroup analysis comparing type and duration of DAPT and associated outcomes among patients with and without CKD (eGFR < 60 ml/min/1.73 m2, calculated by CKD-EPI). Patients with CKD (275/1921, 14.3%) were prescribed prasugrel/ticagrelor less (18.5% vs 25.8%, p = 0.01) and had a shorter duration of DAPT therapy versus patients without CKD (median 382 vs 402 days, p = 0.003). CKD was associated with major adverse cardiovascular events (MACE) at 12 months (p < 0.001) but not bleeding when compared to patients without CKD. CKD was associated with MACE in both patients on prasugrel/ticagrelor (p = 0.017) and those on clopidogrel (p < 0.001) (p for heterogeneity = 0.70). CKD was associated with increased bleeding only among patients receiving prasugrel/ticagrelor (p = 0.007), but not among those receiving clopidogrel (p = 0.64) (p for heterogeneity = 0.036). Patients with CKD had a shorter DAPT duration and were less frequently prescribed potent P2Y12 inhibitors than patients without CKD. Overall, compared with patients without CKD, patients with CKD had higher rates of MACE and similar bleeding rates. However, among those prescribed more potent P2Y12 inhibitors, CKD was associated with more bleeding than those without CKD. Further studies are needed to better define the benefit/risk evaluation, and establish a more tailored and evidence-based DAPT regimen for this high-risk patient group.

Use of antithrombotic therapy for secondary prevention in patients with stable atherosclerotic cardiovascular disease: Insights from the COordinated National Network to Engage Cardiologists in the antithrombotic Treatment of patients with CardioVascular Disease (CONNECT-CVD) study.

BACKGROUND: Although acetylsalicylic acid is the most commonly used antithrombotic agent for the secondary prevention of cardiovascular events, residual atherothrombotic risk has prompted a guideline recommendation for the addition of dual antiplatelet therapy (DAPT) or dual pathway inhibition (DPI) in high vascular risk patients. Accordingly, the CONNECT CVD quality enhancement initiative provides a contemporary "snapshot" of the clinical features and antithrombotic management of atherosclerotic cardiovascular disease (ASCVD) patients in Canada. METHODS: Canadian cardiologists (49 cardiologists from six provinces) undertook a retrospective chart audit of 10 ASCVD patients in their outpatient practice who met the Cardiovascular Outcomes for People Using Anticoagulation Strategy-like criteria from May 2018 to April 2019. RESULTS: Of the 492 (two cardiologists provided 11 patients) enroled, average age was 70 years, 25% were female, 39% had diabetes and 20% had atrial fibrillation. Prior revascularisation was common (percutaneous coronary artery intervention 61%, coronary artery bypass graft 39%), with 31% having multivessel disease. A total of 47% of patients had a Reduction of Atherothrombosis for Continued Health bleeding score of ≥11 (~2.8% risk of serious bleeding at 2 years). Single antiplatelet therapy (SAPT) alone was most commonly used (62%), while 22% were on DAPT alone. In total, 22% were on oral anticoagulation (OAC), with 16% being on non-vitamin K oral anticoagulant alone, 5% on DPI and 1% received triple therapy. CONCLUSIONS: In contemporary Canadian clinical practice of stable ASCVD patients, a large number of patients receive antithrombotic therapy other than SAPT. Further efforts are required to guide the appropriate selection of patients in whom more potent antithrombotic therapies may safely reduce residual risk.

Genome-wide and candidate gene approaches of clopidogrel efficacy using pharmacodynamic and clinical end points-Rationale and design of the International Clopidogrel Pharmacogenomics Consortium (ICPC).

RATIONALE: The P2Y12 receptor inhibitor clopidogrel is widely used in patients with acute coronary syndrome, percutaneous coronary intervention, or ischemic stroke. Platelet inhibition by clopidogrel shows wide interpatient variability, and high on-treatment platelet reactivity is a risk factor for atherothrombotic events, particularly in high-risk populations. CYP2C19 polymorphism plays an important role in this variability, but heritability estimates suggest that additional genetic variants remain unidentified. The aim of the International Clopidogrel Pharmacogenomics Consortium (ICPC) is to identify genetic determinants of clopidogrel pharmacodynamics and clinical response. STUDY DESIGN: Based on the data published on www.clinicaltrials.gov, clopidogrel intervention studies containing genetic and platelet function data were identified for participation. Lead investigators were invited to share DNA samples, platelet function test results, patient characteristics, and cardiovascular outcomes to perform candidate gene and genome-wide studies. RESULTS: In total, 17 study sites from 13 countries participate in the ICPC, contributing individual patient data from 8,829 patients. Available adenosine diphosphate-stimulated platelet function tests included vasodilator-stimulated phosphoprotein assay, light transmittance aggregometry, and the VerifyNow P2Y12 assay. A proof-of-principle analysis based on genotype data provided by each group showed a strong and consistent association between CYP2C19*2 and platelet reactivity (P value=5.1 × 10-40). CONCLUSION: The ICPC aims to identify new loci influencing clopidogrel efficacy by using state-of-the-art genetic approaches in a large cohort of clopidogrel-treated patients to better understand the genetic basis of on-treatment response variability.

Impact of an invasive strategy in the elderly hospitalized with acute coronary syndrome with emphasis on the nonagenarians.

BACKGROUND: Published data about nonagenarians with acute coronary syndrome (ACS) were mainly descriptive and limited by small sample sizes and unadjusted outcomes. We aim to describe the characteristics, management, and the impact of an invasive strategy on major adverse events in elderly patients hospitalized with ACS with focus on the nonagerians. METHODS AND RESULTS: We analyzed data collected as part of the AMI-OPTIMA study, a cluster-randomized study of knowledge translation intervention versus usual care on optimal discharge medications in patients admitted with ACS at 24 Canadian hospitals. To determine whether an invasive strategy improved outcomes in the elderly, we used inverse probability weighting to adjust for confounders between patients who underwent invasive versus conservative strategies. Of 4,569 consecutive patients: 2,395 (52%) were <70 years old, 1,031 (23%) were septuagenarians, 941 (21%) were octogenarians, and 202 (4.4%) were nonagenarians. An invasive strategy was associated with reduced in-hospital all-cause mortality in all age groups: 1.1% versus 3.8% in patients <70 years old (P < 0.001), 2.9% versus 7.4% in septuagenarians (P < 0.001), 5.1% versus 14.7% in octogenarians (P < 0.001), and 12.0% versus 25.1% in nonagenarians (P = 0.001). An invasive strategy was also associated with higher thrombolysis in myocardial infarction major bleeds in the nonagenarians (9.0% vs. 2.0%; P = 0.003). CONCLUSIONS: The reduction in in-hospital mortality associated with an invasive strategy in elderly and nonagenarians presented with ACS is generating hypothesis and merits further studies to confirm these benefits and to guide clinicians in the management of these high-risk patients.

Ischemic and bleeding events in patients with myocardial infarction undergoing percutaneous coronary intervention who require oral anticoagulation: Insights from the Canadian observational AntiPlatelet sTudy.

BACKGROUND: Since the introduction of newer, more potent P2Y12 receptor inhibitors (P2Y12ris), practice patterns and associated clinical outcomes in patients with myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI) and also requiring oral anticoagulation (OAC) have not been fully characterized. METHODS: The Canadian Observational Antiplatelet Study was a prospective, multicenter, longitudinal, observational study (26 hospitals, December 2011 to May 2013) describing P2Y12ri treatment patterns and outcomes in patients with ST-elevation and non-ST-elevation MI undergoing PCI. We describe the clinical characteristics, treatment patterns, bleeding, and ischemic outcomes over the 15-month follow-up within and between the subgroups of patients discharged on either dual-antiplatelet therapy (DAPT) (acetyl salicylic acid [ASA]+P2Y12ri) or triple therapy (ASA+P2Y12ri+OAC). RESULTS: Of the 2,034 patients at discharge, 86% (n = 1,757) were on DAPT, whereas 14% (n = 277) were on triple therapy (50% warfarin, 50% non-vitamin K OAC [NOAC]). The frequency of newer P2Y12ri use (prasugrel or ticagrelor) was similar in the DAPT and triple therapy groups (28% vs 26%, respectively). In the triple therapy group, NOAC use was higher in those receiving a new P2Y12ri compared to those receiving clopidogrel (75% vs 41%, respectively, P < .0001). The unadjusted and adjusted events of major cardiovascular event (MACE) and bleeding were higher in the triple therapy group. For patients on triple therapy, the bleeding or MACE events were not significantly different between those on clopidogrel versus those on ticagrelor or prasugrel. CONCLUSION: In this observational study of MI patients requiring PCI, 1 in 8 were discharged on triple antithrombotic therapy, of whom 26% were on newer P2Y12ris. Patients on triple therapy had higher risk at baseline, with higher unadjusted and adjusted MACE and bleeding events compared to those on DAPT alone. Among triple therapy-treated patients, there was no difference in the MACE and bleeding events regardless of the P2Y12ri used.

Baseline characteristics, adenosine diphosphate receptor inhibitor treatment patterns, and in-hospital outcomes of myocardial infarction patients undergoing percutaneous coronary intervention in the prospective Canadian Observational AntiPlatelet sTudy (COAPT).

BACKGROUND: Contemporary use of dual antiplatelet therapy and consistency with guideline recommendations in acute coronary syndrome patients undergoing percutaneous coronary intervention (PCI) have not been well characterized. METHODS: The COAPT was a prospective, observational, multicenter, longitudinal study of patients with myocardial infarction (MI) undergoing PCI. Baseline characteristics, treatment patterns, processes of care, factors associated with switching to and from novel adenosine diphosphate receptor inhibitors (ADPris), and in-hospital outcomes are described. RESULTS: Among 2,179 MI patients undergoing PCI during their index hospitalization, 1,328 (60.9%) had ST elevation. Initial ADPri use included clopidogrel in 1,812 (83.2%), prasugrel in 125 (5.7%), and ticagrelor in 242 (11.1%). At discharge, 1,597 patients (73.4%) were prescribed clopidogrel, 220 (10.1%) prasugrel, and 358 (16.5%) ticagrelor. Switching between ADPri therapies during the index hospitalization occurred in 15.3%, 22.4%, and 25.2% of patients initially started on clopidogrel, prasugrel, and ticagrelor, respectively. Most switches over the 15-month study period occurred during the index admission (16.8% of patients vs 4.4% switches postdischarge). Major adverse cardiovascular events occurred in 7.5% of patients during the index hospitalization. In-hospital bleeding events occurred in 6.0% of patients and most were mild. CONCLUSIONS: Despite randomized trial evidence and guideline recommendations, only a minority of Canadian MI patients undergoing PCI initially received or were discharged on one of the newer ADPri agents. These findings suggest an opportunity to improve upon the appropriate selection of the ADPris at index hospitalization and discharge in Canadian MI patients undergoing PCI.

Arterial access site and outcomes in patients undergoing percutaneous coronary intervention with and without vorapaxar.

OBJECTIVES: We evaluated outcomes associated with transradial vs. transfemoral approaches and vorapaxar in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) in the TRACER trial. BACKGROUND: Vorapaxar reduces ischemic events but increases the risk of major bleeding. METHODS: We compared 30-day and 2-year major adverse cardiac events (MACE: cardiovascular death, myocardial infarction, stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization) and noncoronary artery bypass graft (CABG)-related bleedings in 2,192 transradial and 4,880 transfemoral patients undergoing PCI after adjusting for confounding variables, including propensity for transradial access. RESULTS: Overall, 30-day GUSTO moderate/severe and non-CABG TIMI major/minor bleeding occurred less frequently in transradial (0.9% vs. 2.0%, P = 0.001) vs. transfemoral (1.1% vs. 2.5%, P = 0.005) patients. A similar reduction was seen at 2 years (3.3% vs. 4.7%, P = 0.008; 3.3% vs. 4.9%, P < 0.001, respectively). Transradial was associated with an increased risk of ischemic events at 30 days (OR 1.38, 95% CI 1.11-1.72; P = 0.004), driven primarily by increased periprocedural myocardial infarctions. At 2 years, rates of MACE were comparable (HR 1.14, 95% CI 0.98-1.33; P = 0.096). Although bleeding rates were higher with vorapaxar in transfemoral vs. transradial patients, there was no significant treatment interaction. Also, the access site did not modulate the association between vorapaxar and MACE. CONCLUSIONS: Transradial access was associated with lower bleeding rates and similar long-term ischemic outcomes, suggesting transradial access is safer than transfemoral access among ACS patients receiving potent antiplatelet therapies. Because of the nonrandomized allocation of arterial access, these results should be considered exploratory. © 2015 Wiley Periodicals, Inc.

Predictors and prognosis of early ischemic mitral regurgitation in the era of primary percutaneous coronary revascularisation.

BACKGROUND: Studies assessing ischemic mitral regurgitation (IMR) comprised of heterogeneous population and evaluated IMR in the subacute setting. The incidence of early IMR in the setting of primary PCI, its progression and clinical impact over time is still undetermined. We sought to determine the predictors and prognosis of early IMR after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). METHODS: Using our primary PCI database, we screened for patients who underwent ≥2 transthoracic echocardiograms early (1-3 days) and late (1 year) following primary PCI. The primary outcomes were: (1) major adverse events (MACE) including death, ischemic events, repeat hospitalization, re-vascularization and mitral repair or replacement (2) changes in quantitative echocardiographic assessments. RESULTS: From January 2006 to July 2012, we included 174 patients. Post-primary PCI IMR was absent in 95 patients (55%), mild in 60 (34%), and moderate to severe in 19 (11%). Early after primary PCI, IMR was independently predicted by an ischemic time > 540 min (OR: 2.92 [95% CI, 1.28 - 7.05]; p = 0.01), and female gender (OR: 3.06 [95% CI, 1.42 - 6.89]; p = 0.004). At a median follow-up of 366 days [34-582 days], IMR was documented in 44% of the entire cohort, with moderate to severe IMR accounting for 15%. During follow-up, MR regression (change ≥ 1 grade) was seen in 18% of patients. Moderate to severe IMR remained an independent predictor of MACE (HR: 2.58 [95% CI, 1.08 - 5.53]; p = 0.04). CONCLUSIONS: After primary PCI, IMR is a frequent finding. Regression of early IMR during long-term follow-up is uncommon. Since moderate to severe IMR post-primary PCI appears to be correlated with worse outcomes, close follow-up is required.

Early and late outcomes after primary percutaneous coronary intervention by radial or femoral approach in patients presenting in acute ST-elevation myocardial infarction and cardiogenic shock.

BACKGROUND: Although radial approach is increasingly used in percutaneous coronary interventions (PCIs) including in acute myocardial infarction (MI), patients with cardiogenic shock have been excluded from comparisons with femoral approach. The aim of our study was to compare clinical outcomes in patients undergoing primary PCI with cardiogenic shock by radial and femoral approach. METHODS AND RESULTS: From 2,663 patients presenting with ST-elevation MI in 2 large volume radial centers, we identified 197 patients (7.4%) with signs of cardiogenic shock immediately before undergoing primary PCI. Radial approach was used in 55% of cases when at least 1 radial artery was weakly palpable, either spontaneously or after intravenous noradrenaline bolus. Patients in the radial group were older (69 ± 12 vs 64 ± 12 years, P = .010), had less diabetes (13% vs 26%, P = .028), and required less often intubation prior PCI (42% vs 66%, P = .0006) or intraaortic balloon pump (36% vs 55%, P = .0096). Mortality at 1 year was 44% in the radial group and 64% in the femoral group (P = .0044). Independent predictors of late mortality included radial approach (hazard ratio [HR] 0.65, 95% CI 0.42-0.98, P = .041), the use of glycoprotein IIb-IIIa receptor inhibitors (HR 0.63, 95% CI 0.40-0.96, P = .032), baseline creatinine ≥110 µmol/L (HR 3.34, 95% CI 2.20-5.12, P < .0001), initial glycemia >200 mg/dL (HR 2.02, 95% CI 1.34-3.11, P = .0008), and age >65 years (HR 1.80, 95% CI 1.18-2.79, P = .006). CONCLUSION: Radial approach was safe and feasible in more than half of the patients with ST-elevation MI and cardiogenic shock treated by primary PCI. After adjustment for baseline and procedural characteristics, radial approach remained associated with better survival. However, prognosis of patients undergoing primary PCI in cardiogenic shock remains poor.

Canada Acute Coronary Syndrome Risk Score: a new risk score for early prognostication in acute coronary syndromes.

BACKGROUND: Despite the availability of several acute coronary syndrome (ACS) prognostic risk scores, there is no appropriate score for early-risk stratification at the time of the first medical contact with patients with ACS. The primary objective of this study is to develop a simple risk score that can be used for early-risk stratification of patients with ACS. METHODS: We derived the risk score from the Acute Myocardial Infarction in Quebec and Canada ACS-1 registries and validated the risk score in 4 other large data sets of patients with ACS (Canada ACS-2 registry, Canada-GRACE, EFFECT-1, and the FAST-MI registries). The final risk score is named the Canada Acute Coronary Syndrome Risk Score (C-ACS) and ranged from 0 to 4, with 1 point assigned for the presence of each of these variables: age ≥75 years, Killip >1, systolic blood pressure <100 mm Hg, and heart rate >100 beats/min. The primary end points were short-term (inhospital or 30-day) and long-term (1- or 5-year) all-cause mortality. RESULTS: The C-ACS has good predictive values for short- and long-term mortality of patients with ST-segment elevation myocardial infarction and non-ST-segment elevation ACS. The negative predictive value of a C-ACS score ≥1 is excellent at ≥98% (95% CI 0.97-0.99) for short-term mortality and ≥93% (95% CI 0.91-0.96) for long-term mortality. In other words, a C-ACS score of 0 can potentially identify correctly ≥97% short-term survivors and ≥91% long-term survivors. CONCLUSION: The C-ACS risk score permits rapid stratification of patients with ACS. Because this risk score is simple and easy to memorize and calculate, it can be rapidly applied by health care professionals without advanced medical training.

Incidence and clinical impact of concurrent chronic total occlusion according to gender in ST-elevation myocardial infarction.

OBJECTIVES: To determine the prevalence of a concurrent CTO in men and women and to examine its impact on mortality. BACKGROUND: The impact of chronic total occlusion (CTO) in patients with ST-elevation myocardial infarction (STEMI) according to gender has not been assessed. METHODS: Patients referred with STEMI were categorized into single vessel disease (SVD), multivessel disease (MVD) without, with 1 or > 1 CTO. The primary end-point was the 1-year mortality. RESULTS: Among the 2020 STEMI patients included between 2006 and 2011, 24% were female. Women were older, had more hypertension and renal failure (P < 0.0001 for all). The prevalence of 1 or > 1 concurrent CTO was similar in both sexes, 7 and 1%, respectively. Early and late mortality was significantly higher in women compared with men (P < 0.0001). In women, the mortality was significantly worse in patients with > 1 CTO (100%) and with 1 CTO (36.4%) compared with those with MVD without CTO (18.4%) or with SVD (10.4%) (P < 0.0001). MVD with and without concurrent CTO were both independent predictors of 1-year mortality in women (HR 3.58; 95 % CI 1.69-7.18 and HR 2.76; 95 % CI 1.33-5.51) whereas only MVD with CTO was predictive in men (HR 2.19; 95% CI 1.20-3.97). CONCLUSIONS: Among unselected STEMI patients, the prevalence of CTO was equal in both sexes whereas early and late mortality remained significantly higher in women. Other factors than the presence of a concurrent CTO must be explored to explain differences in survival after STEMI between women and men.

Antithrombotic therapies in Canadian atrial fibrillation patients with concomitant coronary artery disease: Insights from the CONNECT AF + PCI-II program.

BACKGROUND: Selecting the appropriate antithrombotic regimen for patients with atrial fibrillation (AF) who have undergone percutaneous coronary intervention (PCI) or have had medically managed acute coronary syndrome (ACS) remains complex. This multi-centre observational study evaluated patterns of antithrombotic therapies utilized among Canadian patients with AF post-PCI or ACS. METHODS AND RESULTS: By retrospective chart audit, 611 non-valvular AF patients [median (interquartile range) age 76 (69-83) years, CHADS2 score 2 (1-3)] who underwent PCI or had medically managed ACS between August 2018 and December 2020 were identified by 68 cardiologists across eight provinces in Canada. Overall, triple antithrombotic therapy [TAT: combined oral anticoagulation (OAC) and dual antiplatelet therapy (DAPT)] was the most common initial antithrombotic strategy, with use in 53.8 % of patients, followed by dual pathway therapy (32.7 % received OAC and a P2Y12 inhibitor, and 4.1 % received OAC and aspirin) and DAPT (9.3 %). Median duration of TAT was 30 (7, 30) days. Compared to the previous CONNECT AF + PCI-I program, there was an increased use of dual pathway therapy relative to TAT over time (P-value <.0001). DOACs (direct oral anticoagulants) represented 90.3 % of all OACs used overall, with apixaban being the most utilized (50.5 %). Proton pump inhibitors were used in 57.0 % of all patients, and 70.1 % of patients on ASA. Planned antithrombotic therapies at 1 year were: 76.2 % OAC monotherapy, 8.3 % OAC + ASA, 7.9 % OAC + P2Y12 inhibitor, 4.3 % DAPT, 1.3 % ASA alone, and <1 % triple therapy. CONCLUSION: In accordance with recent Canadian Cardiovascular Society guideline recommendations, we observed an increased use of dual pathway therapy relative to TAT over time in both AF patients post-PCI (elective and emergent) and in those with medically managed ACS. Additionally, DOACs have become the prevailing form of anticoagulation across all antithrombotic regimens. Our findings suggest that Canadian physicians are integrating evidence-based approaches to optimally manage the bleeding and thrombotic risks of AF patients post-PCI and/or ACS.

Deadly association of cardiogenic shock and chronic total occlusion in acute ST-elevation myocardial infarction.

BACKGROUND: The association between cardiogenic shock and 1 or >1 chronic total occlusion (CTO) in unselected patients presenting with ST-elevation myocardial infarction (MI) (STEMI) has not been characterized. METHODS: Patients with STEMI referred with or without cardiogenic shock were categorized into no CTO, 1 CTO, and >1 CTO. The primary end point was the 30-day mortality. RESULTS: Between 2006 and 2011, 2,020 consecutive patients were included. A total of 141 patients (7%) presented with cardiogenic shock on admission. The prevalence of 1 CTO and >1 CTO in a non-infarct-related artery was 23% and 5%, respectively, among patients with shock compared with 6% and 0.5% in patients without shock (P < .0001). Independent predictors of cardiogenic shock included left main-related MI (odds ratio [OR] 6.55, 95% CI 1.39-26.82, P = .019), CTO (OR 4.20, 95% CI 2.64-6.57, P < .001), creatinine clearance <60 mL/min (OR 3.41, 95% CI 2.32-4.99, P < .0001), and left anterior descending-related MI (OR 2.20, 95% CI 1.51-3.23, P < .0001). Thirty-day mortality was 100% in shock patients with >1 CTO, 65.6% with 1 CTO, and 40.2% in patients without CTO (P < .0001). After adjustment for left ventricular ejection fraction and renal function, CTO remained an independent predictor for 30-day mortality (hazard ratio [HR] 1.83; 95% CI 1.10-3.01, P = .02). CONCLUSION: In patients with STEMI, CTO was strongly associated with cardiogenic shock on admission. In this setting, mortality was substantially higher in patients with 1 CTO and exceedingly high in those with >1 CTO. The presence of CTO was an independent predictor of early mortality.

Effects of aspiration thrombectomy on necrosis size and ejection fraction after transradial percutaneous coronary intervention in acute ST-elevation myocardial infarction.

BACKGROUND: The use of routine aspiration thrombectomy in primary percutaneous coronary intervention (PCI) remains controversial. METHODS: Patients in the EArly Discharge after Transradial Stenting of CoronarY Arteries in Acute Myocardial Infarction (n = 105) study were treated with aspirin, clopidogrel, and abciximab within 6 hr of symptoms onset. Operators were allowed to use 6 Fr Export aspiration catheter at their discretion. In this observational analysis, we compared acute and late results in patients treated with and without thrombectomy using cardiac biomarkers, angiographic, cardiovascular magnetic resonance (CMR), and clinical parameters. RESULTS: Patients in the thrombectomy group (n = 44) had longer symptoms to balloon time (196 ± 86 min vs. 164 ± 62, P = 0.039) and higher incidence of preprocedural TIMI flow grade 0 or 1 (84% vs. 64%, P = 0.028). Following PCI, both groups had similar incidence of TIMI flow grade 3 (93 vs. 92%, P = 0.73) and myocardial blush grade 2 or 3 (80 vs. 77%, P = 0.86), respectively. Patients in thrombectomy group had significantly higher post-PCI maximum values of creatine kinase-MB (P = 0.0007) and troponin T (P = 0.0010). Accordingly, post-PCI myocardial necrosis by CMR was higher (P = 0.0030) in patients in the thrombectomy group. At 6-month follow-up, necrosis size remained higher (20.7% ± 13.3% vs. 13.5% ± 11.1%, P = 0.012) in the thrombectomy group. Ejection fraction at 6 months was 65% ± 9% in patients in thrombectomy group compared to 70% ± 11% in patients without (P = 0.070). Results were not affected by initial TIMI flow or symptoms to balloon time. Clinical events remained comparable in both groups at 12 months follow-up. CONCLUSION: In patients with ST-segment elevation myocardial infarction presenting within 6 hr of symptoms and undergoing primary angioplasty with maximal antiplatelet therapy, acute and late results did not suggest significant benefit for additional aspiration thrombectomy, irrespective of initial TIMI flow or total ischemic time.

Racial Disparities in Acute Coronary Syndrome Management Within a Universal Healthcare Context: Insights From the AMI-OPTIMA Trial.

BACKGROUND: Although prior studies have demonstrated racial disparities regarding acute coronary syndrome (ACS) care within private or mixed healthcare systems, few researchers have explored such disparities within universal healthcare systems. We aimed to evaluate the quality and outcomes of in-hospital ACS management for White patients vs patients of colour, within a universal healthcare context. METHODS: We performed a post hoc analysis of the Acute Myocardial Infarction - Knowledge Translation to Optimize Adherence to Evidence-Based Therapy study, a cluster-randomized trial evaluating a knowledge-translation intervention at 24 hospitals in Quebec, Canada (years: 2009 and 2012). The primary endpoint was coronary catheterization. The secondary endpoints included in-hospital mortality, percutaneous and surgical coronary revascularization, major bleeding, total stroke, and discharge prescription of evidence-based medical therapy. RESULTS: Of 3444 included patients, 2738 were White, and 706 were people of colour. The mean age was 68.2 years (33.3% women) among White patients and 69.5 years (36.0% women) among patients of colour. Patients of colour were less likely to undergo in-hospital coronary catheterization than were White patients (74.5% vs 80.3%, P = 0.001). This difference was attenuated after adjusting for patient-level characteristics (odds ratio 0.89; 95% confidence interval 0.73-1.09), and it was eliminated after adjusting for hospital-level characteristics (odds ratio 1.04; 95% confidence interval 0.73-1.49). CONCLUSIONS: Racial disparity in coronary catheterization for ACS persists within a universal healthcare context. Patients' comorbidities and hospital-level factors may be partially responsible for this inequality. Future research on cardiovascular healthcare in patients with diverse racial/ethnic backgrounds in universal healthcare systems is needed to remediate racial inequality in ACS management.

CONTEXTE: Bien que des études antérieures aient démontré l'existence de disparités raciales dans la prise en charge du syndrome coronarien aigu (SCA) au sein de systèmes de santé privés ou mixtes, peu de chercheurs ont étudié ces disparités au sein de systèmes universels de soins de santé. Nous avons cherché à évaluer la qualité et les résultats de la prise en charge du SCA à l'hôpital pour les patients blancs par rapport aux patients de couleur, dans un contexte de soins de santé universels. MÉTHODOLOGIE: Nous avons effectué une analyse a posteriori de l'étude AMI-OPTIMA, un essai sur échantillon en grappes aléatoire évaluant une intervention d'application des connaissances dans 24 hôpitaux du Québec, au Canada (années : 2009 et 2012). Le paramètre d'évaluation principal était le cathétérisme coronaire. Les paramètres d'évaluation secondaires comprenaient la mortalité à l'hôpital, la revascularisation coronaire percutanée et chirurgicale, l'hémorragie majeure, l'accident vasculaire cérébral et la prescription au congé d'un traitement médical fondé sur des données probantes. RÉSULTATS: Sur les 3444 patients étudiés, 2738 étaient blancs et 706 étaient des personnes de couleur. L'âge moyen était de 68,2 ans (33,3 % de femmes) chez les patients blancs, et de 69,5 ans (36,0 % de femmes) chez les patients de couleur. Les patients de couleur étaient moins susceptibles de subir un cathétérisme coronaire à l'hôpital que les patients blancs (74,5 % contre 80,3 %, p = 0,001). Cette différence a été atténuée après ajustement pour tenir compte des caractéristiques des patients (rapport de cotes : 0,89; intervalle de confiance [IC] à 95 % : 0,73-1,09), et éliminée après ajustement pour tenir compte des caractéristiques des hôpitaux (rapport de cotes : 1,04; IC à 95 % : 0,73-1,49). CONCLUSIONS: La disparité raciale en ce qui a trait au cathétérisme coronaire pour un SCA persiste dans un contexte de soins de santé universels. Les comorbidités des patients et des facteurs liés à l'hôpital peuvent être partiellement responsables de cette inégalité. De plus amples recherches sur les soins cardiovasculaires chez les patients de diverses origines raciales ou ethniques dans les systèmes universels de soins de santé sont nécessaires pour remédier aux inégalités raciales dans la prise en charge du SCA.

Provision of a DAPT Score to Cardiologists and Extension of Dual Antiplatelet Therapy Beyond 1 Year After ACS: Randomized Substudy of the Prospective Canadian ACS Reflective II Study.

BACKGROUND: Extension of dual antiplatelet therapy (DAPT) beyond 1 year after acute coronary syndrome is associated with a reduction in ischemic events but also increased bleeding. The DAPT score identifies individuals likely to derive overall benefit or harm from DAPT extension. We sought to evaluate the impact of providing the DAPT score to treating physicians on the decision to extend DAPT beyond 1 year after non-ST-segment elevation myocardial infarction. METHODS: Moderate to high-risk non-ST-segment elevation myocardial infarction patients were enrolled from July 2016 to May 2018 in 13 Canadian hospitals by 52 cardiologists. Participating cardiologists were randomly assigned 1:1 to receive their individual patients' DAPT scores before the 1-year follow-up visit vs not receiving their patients' DAPT scores. Rates of DAPT extension were compared among the randomized groups. RESULTS: At 1 year, 370 of the 585 (63.2%) patients discharged on DAPT were receiving DAPT. Among patients on DAPT at 1 year, the median (25th, 75th percentile) DAPT score was 2 (1,3). DAPT was extended beyond 1 year in 36.2% randomly assigned to provision of DAPT score vs 35.7% in the control group (P = 0.93). In the subgroup of patients with DAPT score ≥ 2, DAPT extension was 49.5% in the DAPT score provision arm vs 40.4% in the control arm (P = 0.22); among patients with DAPT score < 2, DAPT termination was 78.6% in the DAPT score provision arm vs 70.6% in the control arm (P = 0.26) (P value for interaction = 0.1). CONCLUSIONS: In this exploratory randomized trial, provision of the DAPT score to treating physicians had no impact on the duration of DAPT treatment beyond 1 year.

INTRODUCTION: La prolongation de la bithérapie antiplaquettaire au-delà d'un an après un syndrome coronarien aigu est associée à la réduction des accidents ischémiques, mais aussi à l'augmentation des hémorragies. Le score de bithérapie antiplaquettaire permet de déterminer les individus susceptibles d'obtenir des avantages globaux ou des inconvénients de la prolongation de la bithérapie antiplaquettaire. Nous avons cherché à évaluer les répercussions de l'obtention du score de bithérapie antiplaquettaire par les médecins traitants sur la décision quant à la prolongation de la bithérapie antiplaquettaire au-delà d'un an après l'infarctus du myocarde sans élévation du segment ST. MÉTHODES: De juillet 2016 à mai 2018, 52 cardiologues de 13 hôpitaux du Canada ont inscrit des patients exposés à un risque modéré à élevé d'infarctus du myocarde sans élévation du segment ST. Nous avons réparti de façon aléatoire selon un rapport 1:1 les cardiologues participants qui recevaient les scores de bithérapie antiplaquettaire individuels de leurs patients avant la consultation de suivi après un an vs ceux qui ne recevaient pas les scores de bithérapie antiplaquettaire de leurs patients. Nous avons comparé les taux de prolongation de la bithérapie antiplaquettaire des groupes répartis de façon aléatoire. RÉSULTATS: Après un an, 370 (63,2 %) patients sur 585 qui avaient eu à la sortie de l'hôpital une bithérapie antiplaquettaire recevaient la bithérapie antiplaquettaire. Parmi les patients qui prenaient la bithérapie antiplaquettaire après un an, le score médian de bithérapie antiplaquettaire (25e, 75e percentiles) était de 2 (1, 3). La bithérapie antiplaquettaire était prolongée au-delà d'un an chez 36,2 % des patients répartis de façon aléatoire qui avaient un score de bithérapie antiplaquettaire vs 35,7 % dans le groupe témoin (P = 0,93). Dans le sous-groupe de patients qui avaient un score de bithérapie antiplaquettaire ≥ 2, la prolongation de la bithérapie antiplaquettaire était de 49,5 % dans le bras qui avait un score de bithérapie antiplaquettaire vs 40,4 % dans le bras témoin (P = 0,22); parmi les patients qui avaient un score de bithérapie antiplaquettaire < 2, la cessation de la bithérapie antiplaquettaire était de 78,6 % dans le bras qui avait un score de bithérapie antiplaquettaire vs 70,6 % dans le bras témoin (P = 0,26) (valeur P pour l'interaction = 0,1). CONCLUSIONS: Dans cet essai exploratoire à répartition aléatoire, l'obtention du score de la bithérapie antiplaquettaire par les médecins traitants n'a pas engendré de répercussions sur la durée de la bithérapie antiplaquettaire au-delà d'un an.

Contemporary use of guideline-based higher potency P2Y12 receptor inhibitor therapy in patients with moderate-to-high risk non-ST-segment elevation myocardial infarction: Results from the Canadian ACS reflective II cross-sectional study.

BACKGROUND: After myocardial infarction, guidelines recommend higher-potency P2Y12 receptor inhibitors, namely ticagrelor and prasugrel, over clopidogrel. HYPOTHESIS: We aimed to determine the contemporary use of higher-potency antiplatelet therapy in Canadian patients with non-ST-elevation myocardial infarction (NSTEMI). METHODS: A total of 684 moderate-to-high risk NSTEMI patients were enrolled in the prospective Canadian ACS Reflective II registry at 12 Canadian hospitals and three clinics in five provinces between July 2016 and May 2018. Multivariable logistic regression modeling was performed to assess factors independently associated with higher-potency P2Y12 receptor inhibitor use at discharge. RESULTS: At hospital discharge, 78.3% of patients were treated with a P2Y12 receptor inhibitor. Among patients discharged on a P2Y12 receptor inhibitor, use of higher-potency P2Y12 receptor inhibitor was 61.4%. After adjustment, treatment in-hospital with PCI (OR 4.48, 95%CI 3.34-6.03, p < .0001) was most strongly associated with higher use of higher-potency P2Y12 receptor inhibitor, while oral anticoagulant use at discharge (OR 0.03, 95%CI 0.01-0.12, p < .0001), and atrial fibrillation (OR 0.40, 95%CI 0.17-0.98, p = .046) were most strongly associated with lower use of higher-potency P2Y12 receptor inhibitor. Use of higher-potency P2Y12 receptor inhibitor varied across provinces (range, 21.6%-78.9%). DISCUSSION: In contemporary Canadian practice, approximately 60% of moderate-to-high risk NSTEMI patients discharged on a P2Y12 receptor inhibitor are treated with a higher-potency P2Y12 receptor inhibitor. In addition to factors that increase risk of bleeding, interprovincial differences in practice patterns were associated with use of higher-potency P2Y12 receptor inhibitor at discharge. Opportunities remain for further optimization of evidence-based, guideline-recommended antiplatelet therapy use.

Antithrombotic Therapy After Percutaneous Coronary Intervention in Patients With Atrial Fibrillation: Findings From the CONNECT AF+PCI Study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

INTRODUCTION: 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. MÉTHODES: 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 ( Co ordinated N ational N etwork to E ngage Interventional C ardiologists in the Antithrombotic T reatment of Patients With A trial F ibrillation Undergoing P ercutaneous C oronary I ntervention) pour déterminer les schémas de sélection du traitement antithrombotique initial. RÉSULTATS: 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). CONCLUSIONS: 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.

Comparison of plaque sealing with paclitaxel-eluting stents versus medical therapy for the treatment of moderate nonsignificant saphenous vein graft lesions: the moderate vein graft lesion stenting with the taxus stent and intravascular ultrasound (VELETI) pilot trial.

BACKGROUND: The presence of moderate saphenous vein graft (SVG) lesions is a major predictor of cardiac events late after coronary artery bypass grafting. We determined the effects of sealing moderate nonsignificant SVG lesions with paclitaxel-eluting stents (PES) on the prevention of SVG atherosclerosis progression. METHODS AND RESULTS: Patients with at least 1 moderate SVG lesion (30% to 60% diameter stenosis) were randomized either to stenting the moderate SVG lesion with a PES (n=30, PES group) or to medical treatment alone (n=27, medical treatment group). Patients had an angiographic and intravascular ultrasound evaluation of the SVG at baseline and at 12-month follow-up. The primary end points were (1) the ultrasound SVG minimal lumen area at follow-up and (2) the changes in ultrasound atheroma volume in an angiographically nondiseased SVG segment. Mean time from coronary artery bypass grafting was 12+/-6 years, and mean low-density lipoprotein cholesterol level was 73+/-31 mg/dL. A total of 70 moderate SVG lesions (39+/-7% diameter stenosis) were evaluated. Significant disease progression occurred in the medical treatment group at the level of the moderate SVG lesion (decrease in minimal lumen area from 6.3+/-3.0 to 5.6+/-3.1 mm(2); P<0.001), leading to a severe flow-limiting lesion or SVG occlusion in 22% of the patients compared with none in the PES group (P=0.014). In the PES group, mean minimal lumen area increased (P<0.001) from 6.1+/-2.2 to 8.6+/-2.9 mm(2) at follow-up (P=0.001 compared with the medical treatment group at 12 months). There were no cases of restenosis or stent thrombosis. No significant atherosclerosis progression occurred at the nonstented SVG segments. At 12-month follow-up, the cumulative incidence of major adverse cardiac events related to the target SVG was 19% in the medical treatment group versus 3% in the PES group (P=0.091). CONCLUSIONS: Stenting moderate nonsignificant lesions in old SVGs with PES was associated with a lower rate of SVG disease progression and a trend toward a lower incidence of major adverse cardiac events at 1-year follow-up compared with medical treatment alone, despite very low low-density lipoprotein cholesterol values. This pilot study supports further investigation into the role of plaque sealing in SVGs. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT002289835.

Management patterns of non-ST segment elevation acute coronary syndromes in relation to prior coronary revascularization.

BACKGROUND: Contemporary guidelines support an early invasive strategy for non-ST elevation acute coronary syndrome (NSTE-ACS) patients who had prior coronary revascularization. However, little is known about the management pattern of these patients in "real world." METHODS: We analyzed 3 consecutive Canadian registries (ACS I, ACS II, and Global Registry of Acute Coronary Events [GRACE]/expanded-GRACE) that recruited 12,483 NSTE-ACS patients from June 1999 to December 2007. We stratified the study population according to prior coronary revascularization status into 4 groups and compared their clinical characteristics, in-hospital use of medications, and cardiac procedures. RESULTS: Of the 12,483 NSTE-ACS patients, 71.2% had no prior revascularization, 14.2% had percutaneous coronary intervention (PCI) only, 9.5% had coronary artery bypass graft surgery (CABG) only, and 5% had both PCI and CABG. Compared to their counterparts without prior revascularization, patients with previous PCI and/or CABG were more likely to be male, to have diabetes, myocardial infarction, and heart failure but less likely to have ST-segment deviation or positive cardiac biomarker on presentation. Early use of evidence-based medications was higher among patients with previous PCI only and lower among patients with previous CABG only. After adjusting for possible confounders including GRACE risk score, prior PCI was independently associated with in-hospital use of cardiac catheterization (adjusted odds ratio [OR] 1.18, 95% CI 1.04-1.34, P = .008). In contrast, previous CABG was an independent negative predictor (adjusted OR .77, 95% CI 0.68-0.87, P < .001). There was no significant interaction (P = .93) between previous PCI and CABG. CONCLUSIONS: The NSTE-ACS patients with previous PCI were more likely to be treated invasively. Conversely, patients with prior CABG less frequently received invasive therapy. Future studies should determine the appropriateness of this treatment discrepancy.