Elsevier

Canadian Journal of Cardiology

Volume 27, Issue 2, March–April 2011, Pages 208-221
Canadian Journal of Cardiology

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

https://doi.org/10.1016/j.cjca.2010.12.033Get rights and content

Abstract

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/.

Résumé

Les agents antiplaquettaires sont une des pierres angulaires du traitement des patients ayant une maladie vasculaire athérosclérotique. Les lignes directrices qui portent sur l'utilisation des médicaments antiplaquettaires chez les patients qui manifestent ou qui sont à risque élevé de maladie cardiovasculaire sont à l'heure actuelle incomplètes. Le comité canadien sur les directives pour le traitement antiplaquettaire a passé en revue les lignes directrices des maladies et, subséquemment la littérature publiée, et les revues et l'opinion des experts pour développer des lignes directrices sur l'utilisation de traitements antiplaquettaires dans la prise en charge externe des patients. Ce sommaire exécutif fournit une version abrégée des principales recommandations. Le traitement antiplaquettaire semble généralement sous-utilisé, peut-être en partie en raison de l'absence de directives claires et prouvées. Ici, nous donnons des lignes directrices spécifiques pour la prévention secondaire chez les patients en soins externes à la suite de syndromes coronaires aigus, d'une intervention coronaire percutanée, d'un pontage aortocoronarien; chez les patients avec une histoire d'ischémies cérébrales transitoires ou d'accidents vasculaires cérébraux, et chez les patients avec une maladie artérielle périphérique. Les questions liées à la prévention primaire sont aussi abordées, en plus des contextes cliniques particuliers comme le diabète, l'insuffisance cardiaque, la maladie rénale chronique, la grossesse ou l'allaitement, et la gestion périopératoire.

Des recommandations sont données tant pour les interactions pharmacologiques qui peuvent survenir durant un traitement combiné avec la warfarine, le clopidogrel et les inhibiteurs de la pompe à protons, ou l'aspirine et les médicaments anti-inflammatoires non stéroïdaux, que pour la gestion des complications hémorragiques. Le document entier des lignes directrices a été publié dans un numéro supplémentaire du Journal canadien de cardiologie et est disponible au http://www.ccs.ca/.

Section snippets

Role of the Funding Source

Funding for the preparation of the Canadian Antiplatelet Therapy Guideline was provided by the Thrombosis Interest Group of Canada (TIGC), a registered nonprofit, noncommercial organization dedicated to furthering education and research in the prevention and treatment of thrombosis. Although several members of the working group are members of the TIGC, the TIGC as an entity had no input into the content of the guideline. The funding provided by the TIGC was used to support the creation of a

Antiplatelet Therapy for Secondary Prevention in the First Year Following an Acute Coronary Syndrome

Working Group: Jean-François Tanguay, MD, CSPQ, FRCPC, FACC, FAHA, FESC, Michael P. Love, MB, ChB, MD, MRCP, and Robert C. Welsh, MD, FRCP, FACC

Data from randomized clinical trials demonstrate that compared with acetylsalicylic acid (ASA) alone, combination therapy with oral P2Y12 receptor antagonists improves clinical outcomes in patients with acute coronary syndrome (ACS), although the combination therapy does increase the risk of bleeding.7, 8, 9, 10, 11 Evidence from the CURE Clopidogrel in

Antiplatelet Therapy for Secondary Prevention in the First Year Following PCI

Working Group: Jean-François Tanguay, MD, CSPQ, FRCPC, FACC, FAHA, FESC, Michael P. Love, MB, ChB, MD, MRCP, and Robert C. Welsh, MD, FRCP, FACC

Similar to what is observed in ACS, combination therapy with an oral P2Y12 receptor antagonist and ASA is superior to ASA alone in patients who undergo PCI. Evidence from the PCI-CURE12 and PCI-Clopidogrel as Adjunctive Reperfusion Therapy13 studies established the efficacy of dual ASA and clopidogrel therapy in patients with NSTEACS and STEMI,

Antiplatelet Therapy for Secondary Prevention Beyond 1 Year Following ACS or PCI

Working Group: Anil Gupta, MD, FRCPC, and Pierre Théroux, MD

As shown in the post-ACS and post-PCI sections of the guideline, combination therapy with an oral P2Y12 antagonist and ASA is recommended for up to 1 year following the event. Beyond this timeframe, the most studied, commonly used antiplatelet therapy is ASA monotherapy,20, 21, 22 with the evidence suggesting that doses greater than 75 to 81 mg once daily do not provide additional clinical benefit but increase the risk of bleeding.21

Antiplatelet Therapy for Secondary Prevention Following CABG

Working Group: Raymond Cartier, MD

ASA is recognized as the standard of care for preventing saphenous vein graft closure after CABG and is generally continued indefinitely, given its benefit in preventing subsequent clinical events.25 A large meta-analysis showed that low (approximately 100 mg) and medium (approximately 325 mg) daily doses of ASA were more effective than high-dose (approximately 975 mg) ASA in preventing saphenous vein graft occlusion and caused less gastrointestinal side

Antiplatelet Therapy for the Secondary Prevention of Cerebrovascular Disease

Working Group: Ashfaq Shuaib, MD, FRCP, and Philip Teal, MD, FRCP

For secondary prevention in patients with TIA or ischemic stroke, antiplatelet therapy regimens with proven efficacy include ASA monotherapy,31 ticlopidine monotherapy,32, 33 clopidogrel monotherapy,23, 24 and the combination of ASA and dipyridamole.34, 35, 36 As demonstrated in both the Management of Atherothrombosis for Continued Health and the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management,

Antiplatelet Therapy for Vascular Prevention in Patients With PAD

Working Group: André Roussin, MD, FRCPC, and Thomas F. Lindsay, MD, CM, FRCSC

For patients with asymptomatic PAD (ie, patients with a bruit along major vessels or reduced or absent peripheral pulsations, an abnormally enlarged artery leading to suspicion of an aneurysm, or an ankle-brachial index ≤ 0.9), the limited evidence does not support a benefit for antiplatelet therapy.41, 42 Data do suggest a benefit for ASA monotherapy and clopidogrel monotherapy in patients with symptomatic PAD (ie,

Antiplatelet Therapy for the Primary Prevention of Vascular Events

Working Group: Alan D. Bell, MD, CCFP, and James D. Douketis, MD, FRCP

For the purpose of this guideline, primary prevention is defined as antiplatelet strategies, administered to individuals free of any evidence of manifest atherosclerotic disease in any vascular bed, to prevent clinical vascular events or manifestations thereof. These include, but are not limited to, syndromes of angina pectoris, myocardial infarction, ischemic stroke, TIA, intermittent claudication, and critical limb ischemia.

Use of Antiplatelet Therapy in Patients With Diabetes

Working Group: Maria E. Kraw, MD, FRCP, and Rémi Rabasa-Lhoret, MD, PhD

The results of several observational studies,55, 56 subgroup analyses of randomized clinical trials,52, 53, 57 the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes,58 and Prevention of Progression of Arterial Disease and Diabetes42 trials conducted specifically in patients with diabetes, and several meta-analyses22, 59, 60 suggest that ASA therapy for primary prevention may confer similar, or even

Use of Antiplatelet Therapy in Patients With HF

Working Group: Alan D. Bell, MD, CCPF, and James D. Douketis, MD, FRCP

Trials designed to investigate the role of antithrombotic and antiplatelet therapies in reducing thromboembolic events in patients with HF have failed to consistently demonstrate benefit. Early studies of warfarin in HF demonstrated significant benefit, but results were confounded by inclusion of large numbers of patients with atrial fibrillation and valvular heart disease.64, 65, 66, 67 A meta-analysis of the

Use of Antiplatelet Therapy in Patients With Chronic Kidney Disease

Working Group: Neesh Pannu, MD, SM, FRCP, and Alan D. Bell, MD, CCFP

There is little high-quality evidence to guide the use of ASA or other antiplatelet agents in patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD). A meta-analysis of studies of antiplatelet therapy for maintenance of access patency among dialysis patients demonstrated a significant reduction in the relative risk of serious vascular events associated with antiplatelet therapy, mainly ASA.43 The small

Use of Antiplatelet Therapy in Women Who Are Pregnant or Breastfeeding

Working Group: Wee Shian Chan, MD, FRCP

There are no clinical trials demonstrating the efficacy of antiplatelet therapy or relative superiority of types of antiplatelet therapy in pregnant women with coexisting cardio- or cerebrovascular diseases. Data from randomized trials in which the benefits of ASA were investigated for primary and secondary prevention of preeclampsia and improved pregnancy rates in women who undertake assisted reproductive technology suggest that ASA use does not increase

Management of Patients on Antiplatelet Therapy Who Require a Surgical or Other Invasive Procedure

Working Group: James D. Douketis, MD, FRCPC, and A. Graham Turpie, MD

The majority of evidence for the management of perioperative antiplatelet therapy comes from case-control studies. These studies suggest that continuing ASA monotherapy is safe for patients undergoing gastrointestinal endoscopy,93 polypectomy,94 bronchoscopy,95 dental procedures,96, 97 dermatologic procedures,98, 99, 100 and cataract removal.101 The evidence for clopidogrel monotherapy or combined ASA/clopidogrel therapy in

Management of Antiplatelet Therapy in Association With Minor Bleeding

Working Group: James D. Douketis, MD, FRCP, and A. Graham Turpie, MD

In patients receiving antiplatelet drugs, non–life-threatening minor bleeding is common, particularly in those also receiving anticoagulant therapy (warfarin or heparin) or systemic corticosteroids or with comorbidities such as chronic renal or hepatic disease. In general, minor bleeding is self-limiting and does not require medical attention. Studies specifically assessing the incidence, consequence, and clinical management of

Combination Therapy With Warfarin and ASA: When to Use, When to Consider, When to Avoid

Working Group: James D. Douketis, MD, FRCP, and A. Graham Turpie, MD

In patients with both atrial fibrillation and CAD, relevant data to assess the efficacy of combined warfarin-ASA compared with warfarin alone is derived from a subgroup analysis of warfarin-treated patients in the Stroke Prevention Using an Oral Thrombin Inhibitor in Atrial Fibrillation trials, which compared warfarin (target INR, 2.0-3.0) with ximelagatran for stroke prevention in patients with atrial fibrillation.113 This

Interaction Between Clopidogrel and Proton Pump Inhibitors

Working Group: Wee Shian Chan, MD, FRCP, and Alan D. Bell, MD, CCFP

As many as two-thirds of clopidogrel recipients receive a proton pump inhibitor (PPI) for the treatment of a concomitant acid-related disorder.118 Several pharmacodynamic interaction studies suggest that omeprazole reduces the antiplatelet effect of clopidogrel,119, 120, 121, 122 and results of observational studies have raised concerns that the dual use of clopidogrel and a PPI might lead to an increased risk of adverse

Interaction Between ASA and Nonsteroidal Anti-Inflammatory Drugs

Working Group: Alan D. Bell, MD, CCFP, and Wee Shian Chan, MD, FRCP

Although no randomized trials examining the clinical effect of an interaction between ASA and nonsteroidal anti-inflammatory drugs (NSAIDs) have been completed, laboratory studies135, 136, 137, 138, 139, 140 and observational and epidemiologic data141, 142, 143, 144, 145 have suggested an adverse effect. This interaction has important clinical consequences because, unlike coxibs, traditional NSAIDs may inhibit ASA binding to

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    • Cited by (0)

    The full paper corresponding to this Executive Summary will be published as a supplement to the Canadian Journal of Cardiology May/June issue.

    The disclosure information of the authors and reviewers is available from the CCS on the following websites: www.ccs.ca and www.ccsguidelineprograms.ca.

    This statement was developed following a thorough consideration of medical literature and the best available evidence and clinical experience. It represents the consensus of a Canadian panel comprised of multidisciplinary experts on this topic with a mandate to formulate disease-specific recommendations. These recommendations are aimed to provide a reasonable and practical approach to care for specialists and allied health professionals obliged with the duty of bestowing optimal care to patients and families, and can be subject to change as scientific knowledge and technology advance and as practice patterns evolve. The statement is not intended to be a substitute for physicians using their individual judgment in managing clinical care in consultation with the patient, with appropriate regard to all the individual circumstances of the patient, diagnostic and treatment options available and available resources. Adherence to these recommendations will not necessarily produce successful outcomes in every case.

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