Michael P. Love

The Use of Antiplatelet Therapy in the Outpatient Setting: Canadian Cardiovascular Society Guidelines

Antiplatelet agents are a cornerstone of therapy for patients with atherosclerotic vascular disease. There is presently a lack of comprehensive guidelines focusing on the use of antiplatelet drugs in patients currently manifesting or at elevated risk of cardiovascular disease. The Canadian Antiplatelet Therapy Guidelines Committee reviewed existing disease-based guidelines and subsequently published literature and used expert opinion and review to develop guidelines on the use of antiplatelet therapy in the outpatient setting. This full document has been summarized in an Executive Summary published in the Canadian Journal of Cardiology and may be found at http://www.ccs.ca/. Antiplatelet therapy appears to be generally underused, perhaps in part because of a lack of clear, evidence-based guidance. Here, we provide specific guidelines for secondary prevention in patients discharged from hospital following acute coronary syndromes, post-percutaneous coronary intervention, post-coronary artery bypass grafting, patients with a history of transient cerebral ischemic events or strokes, and patients with peripheral arterial disease. Issues related to primary prevention are also addressed, in addition to special clinical contexts such as diabetes, heart failure, chronic kidney disease, pregnancy/lactation, and perioperative management. Recommendations are provided regarding pharmacologic interactions that may occur during combination therapy with warfarin, clopidogrel and proton-pump inhibitors, or acetylsalicylic acid and nonsteroidal anti-inflammatory drugs, as well as for the management of bleeding complications.

Dual antiplatelet therapy in patients requiring urgent coronary artery bypass grafting surgery: A position statement of the Canadian Cardiovascular Society

UNLABELLED Acute coronary syndrome (ACS) guidelines recommend that most patients receive dual antiplatelet therapy with clopidogrel and acetylsalicylic acid (ASA) at the time of presentation to prevent recurrent ischemic events. Approximately 10% of ACS patients require coronary artery bypass grafting surgery (CABG) during the index admission. Most studies show that patients who receive ASA and clopidogrel within five days of CABG have an increase in operative bleeding. Current consensus guidelines recommend discontinuation of clopidogrel therapy at least five days before planned CABG to reduce bleeding-related events. However, high-risk individuals may require urgent surgery without delay, to reduce the risk of potentially fatal ischemic events. The present multidisciplinary position statement provides evidence- based recommendations for the optimal use of dual antiplatelet therapy to balance ischemic and bleeding risks in patients with recent ACS who may require urgent CABG. RECOMMENDATIONS 1. All ACS patients should be considered for dual antiplatelet therapy with ASA and clopidogrel at the earliest opportunity, despite the possibility of a need for urgent CABG. 2. For patients who have received clopidogrel and ASA, and require CABG: * Those at high risk of an early fatal event (eg, with refractory ischemia despite optimal medical treatment, and with high-risk coronary anatomy (eg, severe left main stenosis with severe right coronary artery disease), should be considered for early surgery without discontinuation of clopidogrel. * In patients with a high bleeding risk (eg, previous surgery, complex surgery) who are also at high risk for an ischemic event, consideration should be given to discontinuing clopidogrel for three to five days before surgery. * Patients at a lower risk for ischemic events (most patients) should have clopidogrel discontinued five days before surgery. 3. For patients who have CABG within five days of receiving clopidogrel and ASA, the risk of major bleeding and transfusion can be minimized by applying multiple strategies before and during surgery. 4. Patients who receive clopidogrel pre-CABG for a recent ACS indication should have clopidogrel restarted after surgery to decrease the risk of recurrent ACS. 5. For patients with a recent coronary stent, the decision to continue clopidogrel until the time of surgery or to discontinue will depend on the risk and potential impact of stent thrombosis. Restarting clopidogrel after CABG will depend on whether the stented vessel was revascularized, the type of stent and the time from stent implantation. Clopidogrel should be restarted when hemostasis is assured to prevent recurrent acute ischemic events.

Retrograde recanalization of chronic total occlusions from the transradial approach; Early canadian experience†

Background: Retrograde approach for chronic total occlusions (CTO) improves recanalization success rates. Eight French (Fr) catheters and the femoral approach are advocated. Objectives: Evaluate whether transradial operators can achieve similar success rates using smaller catheters. Methods: This is a single‐operator series of 42 consecutive cases performed between January and December 2010, including 13 while demonstrating CTO recanalization. Patients were referred because of complexity of the CTO or after failed attempt. Results: Most frequent indications for recanalization were CCS 3–4 angina (52%) and CCS 1–2 in 21%. Eighteen (43%) patients underwent previous failed attempts. CTO was in the right coronary in 74%, left anterior descending in 24%, and a left main in 1. Most lesions (88%) were ≥20 mm long and 52% were calcified. We used septal collateral channels (CC) in 33 (79%), epicardial CC in 8 (20%), and a saphenous vein graft in one case. Radial access was used in all patients and was bilateral in 37 (88%). Five cases required one radial and one femoral access. Six French guides were used in 91% for the retrograde side and 71% for the antegrade side. Otherwise, 7 Fr guides were used. The Corsair® was used in 38 (90%). Procedural success was achieved in 37 (88%), mostly using reverse controlled antegrade–retrograde tracking (60%) or retrograde crossing (29%). The average <24‐h Hb drop was 0.75 ± 0.84 g/dl. No in‐hospital major cardiac events occurred. Conclusion: Transradial retrograde CTO recanalization is feasible, safe, and still associated with high success rates despite the use of smaller guide catheters.

The Use of Antiplatelet Therapy in the Outpatient Setting: Canadian Cardiovascular Society Guidelines Executive Summary

Antiplatelet agents are a cornerstone of therapy for patients with atherosclerotic vascular disease. There is presently a lack of comprehensive guidelines focusing on the use of antiplatelet drugs in patients currently manifesting or at elevated risk of cardiovascular disease. The Canadian Antiplatelet Therapy Guidelines Committee reviewed existing disease-based guidelines and subsequently published literature and used expert opinion and review to develop guidelines on the use of antiplatelet therapy in the outpatient setting. This Executive Summary provides an abbreviated version of the principal recommendations. Antiplatelet therapy appears to be generally underused, perhaps in part because of a lack of clear, evidence-based guidance. Here, we provide specific guidelines for secondary prevention in patients discharged from hospital after acute coronary syndromes, percutaneous coronary intervention, or coronary artery bypass grafting; patients with a history of transient cerebral ischemic events or strokes; and patients with peripheral arterial disease. Issues related to primary prevention are also addressed, in addition to special clinical contexts such as diabetes, heart failure, chronic kidney disease, pregnancy or lactation, and perioperative management. Recommendations are provided regarding pharmacologic interactions that may occur during combination therapy with warfarin, clopidogrel, and proton-pump inhibitors, or aspirin and nonsteroidal anti-inflammatory drugs, as well as for the management of bleeding complications. The complete guidelines document is published as a supplementary issue of the Canadian Journal of Cardiology and is available at http://www.ccs.ca/.

The Canadian Association of Interventional Cardiology and the Canadian Cardiovascular Society joint statement on drug-eluting stents

Recent reports of late stent thrombosis events following deployment of drug-eluting stents (DES) have raised concerns about their safety and role in the management of coronary artery disease. The Canadian Association of Interventional Cardiology and the Canadian Cardiovascular Society have carefully examined the available evidence, including the data presented at the recent Food and Drug Administration Circulatory System Devices Advisory Panel meeting. The purpose of the present statement is to summarize the available evidence relating to DES thrombosis and to provide practical recommendations regarding DES use and antiplatelet therapy.

2018 Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology Focused Update of the Guidelines for the Use of Antiplatelet Therapy

Antiplatelet therapy (APT) has become an important tool in the treatment and prevention of atherosclerotic events, particularly those associated with coronary artery disease. A large evidence base has evolved regarding the relationship between APT prescription in various clinical contexts and risk/benefit relationships. The Guidelines Committee of the Canadian Cardiovascular Society and Canadian Association of Interventional Cardiology publishes regular updates of its recommendations, taking into consideration the most recent clinical evidence. The present update to the 2011 and 2013 Canadian Cardiovascular Society APT guidelines incorporates new evidence on how to optimize APT use, particularly in situations in which few to no data were previously available. The recommendations update focuses on the following primary topics: (1) the duration of dual APT (DAPT) in patients who undergo percutaneous coronary intervention (PCI) for acute coronary syndrome and non-acute coronary syndrome indications; (2) management of DAPT in patients who undergo noncardiac surgery; (3) management of DAPT in patients who undergo elective and semiurgent coronary artery bypass graft surgery; (4) when and how to switch between different oral antiplatelet therapies; and (5) management of antiplatelet and anticoagulant therapy in patients who undergo PCI. For PCI patients, we specifically analyze the particular considerations in patients with atrial fibrillation, mechanical or bioprosthetic valves (including transcatheter aortic valve replacement), venous thromboembolic disease, and established left ventricular thrombus or possible left ventricular thrombus with reduced ejection fraction after ST-segment elevation myocardial infarction. In addition to specific recommendations, we provide values and preferences and practical tips to aid the practicing clinician in the day to day use of these important agents.

Determinants of Percutaneous Coronary Intervention vs Coronary Artery Bypass Grafting: An Interprovincial Comparison

BACKGROUND Marked variation exists concerning the utilization of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). The objective of this study was to examine differences in predictors of mode of revascularization across 3 provincial jurisdictions. METHODS All patients who underwent PCI and isolated CABG in British Columbia, Alberta, and Nova Scotia between 1996 and 2007 were considered. Age- and sex-standardized rates of PCI and CABG per 100,000 population and PCI to CABG ratios were calculated by year and province. Logistic regression models were constructed to identify independent predictors of mode of revascularization in each province. RESULTS A total of 32,190 and 69,409 patients underwent CABG and PCI, respectively, during the study period. Significant increases in the age- and sex-adjusted PCI to CABG ratios were observed in all 3 provinces, but these ratios differed between provinces. Across all 3 jurisdictions, female sex and diagnosis of acute coronary syndrome favoured increased PCI vs CABG, and increased age, left main, or 3-vessel disease occurring before myocardial infarction, and diabetes favoured lower PCI vs CABG. After adjusting for clinical and angiographic factors, there remained a significant variation in choice of PCI vs CABG between the 3 provinces over time. CONCLUSIONS Significant interprovincial variability in PCI to CABG ratios was observed. Though certain patient-related factors predictive of either PCI or CABG were identified, factors beyond clinical presentation played a role in the choice of revascularization approach.

Characteristics and Evidence-Based Management of Stable Coronary Artery Disease Patients in Canada Compared With the Rest of the World: Insights From the CLARIFY Registry

BACKGROUND Previous Canadian high vascular risk registries have demonstrated suboptimal goal-directed reductions in cardiovascular risk factors and underutilization of guideline-recommended therapies in part because of physician underestimation of cardiovascular risk. METHODS The Prospective Observational Longitudinal Registry of Patients With Stable Coronary Artery Disease (CLARIFY) registry enrolled 33,438 stable coronary artery disease patients in 45 countries. In Canada, supplemental information was obtained specifying reasons that patients were not taking guideline-recommended medications. RESULTS In Canada, 1232 patients (9 provinces, 110 physicians) were enrolled and in comparison with the rest of the world, there were several differences in cardiovascular risk factors and medical history; in addition, the Canadian cohort had undergone less percutaneous coronary intervention, but more coronary artery bypass grafting. Among the Canadian cohort, many still continue to smoke (13%) and many do not meet secondary prevention targets for waist circumference (54%), body mass index (81%), physical activity (71%), cholesterol (43%), and systolic blood pressure (20%). Nevertheless, the use of guideline-recommended cardiovascular therapy was high and >90% reported partial/full financial coverage for medications. The number of patients not receiving guideline-recommended therapies because of apparent underestimation of risk was particularly low for antiplatelet agents (2%), β-blockers (11%), and lipid-lowering therapies (1%). CONCLUSIONS Canadian patients with stable coronary artery disease did not meet several guideline-recommended secondary prevention targets, despite high use of evidence-based therapy, extensive financial coverage for these medications, and low physician underestimation of risk. Additional work is needed to identify and address the remaining barriers to effective risk factor control.

Randomized Comparison of Ridaforolimus-Eluting and Zotarolimus-Eluting Coronary Stents in Patients with Coronary Artery Disease: Primary Results from the BIONICS Trial

Background —The safety and efficacy of a novel cobalt alloy-based coronary stent with a durable elastomeric polymer eluting the antiproliferative agent ridaforolimus for treatment of patients with coronary artery disease is undetermined. Methods —A prospective, international 1:1 randomized trial was conducted to evaluate in a noninferiority design the relative safety and efficacy of ridaforolimus-eluting stents (RES) and slow-release zotarolimus-eluting stents (ZES) among 1,919 patients at 76 centers undergoing percutaneous coronary intervention. Inclusion criteria allowed enrollment of patients with recent myocardial infarction (MI), total occlusions, bifurcations lesions and other complex conditions. Results —Baseline clinical and angiographic characteristics were similar between the groups. Overall, mean age was 63.4 years, 32.5% were diabetic and 39.7% presented with acute coronary syndromes. At 12 months, the primary endpoint of target lesion failure (composite of cardiac death, target vessel-related MI and target lesion revascularization) was 5.4% for both devices (upper bound of one-sided 95% confidence interval 1.8%, P noninferiority =0.001). Definite/probable stent thrombosis rates were low in both groups (0.4% RES vs. 0.6% ZES, P=0.75). 13-month angiographic in-stent late lumen loss was 0.22 ± 0.41 mm and 0.23 ± 0.39 mm ( P noninferiority =0.004) for the RES and ZES groups, respectively, and intravascular ultrasound percent neointimal hyperplasia was 8.10 ± 5.81 and 8.85 ± 7.77, respectively ( P noninferiority =0.01). Conclusions —In the present trial which allowed broad inclusion criteria, the novel RES met the prespecified criteria for noninferiority compared with ZES for the primary endpoint of target lesion failure at 12 months, and had similar measures of late lumen loss. These findings support the safety and efficacy of RES in patients representative of clinical practice. Clinical Trial Registration —URL: www.ClinicalTrials.gov Unique Identifier: NCT01995487Background: The safety and efficacy of a novel cobalt alloy-based coronary stent with a durable elastomeric polymer eluting the antiproliferative agent ridaforolimus for treatment of patients with coronary artery disease is undetermined. Methods: A prospective, international 1:1 randomized trial was conducted to evaluate in a noninferiority design the relative safety and efficacy of ridaforolimus-eluting stents (RESs) and slow-release zotarolimus-eluting stents among 1919 patients undergoing percutaneous coronary intervention at 76 centers. Inclusion criteria allowed enrollment of patients with recent myocardial infarction, total occlusions, bifurcations lesions, and other complex conditions. Results: Baseline clinical and angiographic characteristics were similar between the groups. Overall, mean age was 63.4 years, 32.5% had diabetes mellitus, and 39.7% presented with acute coronary syndromes. At 12 months, the primary end point of target lesion failure (composite of cardiac death, target vessel-related myocardial infarction, and target lesion revascularization) was 5.4% for both devices (upper bound of 1-sided 95% confidence interval 1.8%, Pnoninferiority=0.001). Definite/probable stent thrombosis rates were low in both groups (0.4% RES versus 0.6% zotarolimus-eluting stent, P=0.75); 13-month angiographic in-stent late lumen loss was 0.22±0.41 mm and 0.23±0.39 mm (Pnoninferiority=0.004) for the RES and zotarolimus-eluting stent groups, respectively, and intravascular ultrasound percent neointimal hyperplasia was 8.10±5.81 and 8.85±7.77, respectively (Pnoninferiority=0.01). Conclusions: In the present trial, which allowed broad inclusion criteria, the novel RESs met the prespecified criteria for noninferiority compared with zotarolimus-eluting stents for the primary end point of target lesion failure at 12 months and had similar measures of late lumen loss. These findings support the safety and efficacy of RESs in patients who are representative of clinical practice. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01995487.

Adult Congenital Heart Disease Intervention: The Canadian Landscape

Once considered a childhood disease, the number of adults living with congenital heart disease (CHD) has now exceeded the number of pediatric patients. The landscape of percutaneous intervention for adult congenital heart disease (ACHD) has evolved over the past decade and has yet to be characterized in Canada. The aim of this study was to begin to understand the current infrastructure underlying ACHD interventions in Canada and to characterize the type and number of interventions being carried out across the country. A cross-sectional national survey was distributed by e-mail to all cardiac catheterization laboratory directors in 2015. All Canadian laboratories involved in ACHD interventions responded, encompassing 19 institutions spanning 69 cardiac catheterization laboratories. A total of 1451 percutaneous interventions were recorded. Nationwide, the most common simple ACHD interventions were for atrial septal defect and patent foramen ovale closures. The most common ACHD interventions of increased complexity were for coarctation stenting and transcatheter pulmonary valve implantation. There was a marked clustering of procedures in Ontario, Québec, British Columbia, and Alberta in keeping with Canadas population-density distribution. A total of 23 ACHD operators were identified, half of whom had ACHD-specific fellowship training. These data can be used as a starting point to inform the present state of affairs in the area and lay the groundwork for further work to assess resource allocation and human resource planning for the care of patients with ACHD in Canada.