New antithrombotic drugs: a revolution in stroke management (original) (raw)
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European Heart Journal - Cardiovascular Pharmacotherapy
Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia and is associated with an increased risk of cardioembolic stroke. Oral anticoagulation reduces the risk of thromboembolism in patients with AF by about two-thirds compared with placebo but this comes at some cost of an increased risk of bleeding. 1-4 In this issue of the journal, Dr. Benz and co-workers from Canada aimed to systematically assess the effects of antiplatelets on clinical outcomes in patients with atrial fibrillation (AF), treated and not treated with oral anticoagulation. A total of 18 trials including 21 518 participants met the pre-specified eligibility criteria. The authors concluded that in patients with AF not receiving oral anticoagulation, antiplatelet therapy modestly reduced stroke. There was a corresponding signal for harm when used on top of anticoagulation. Irrespective of background anticoagulation use, antiplatelet therapy significantly increased bleeding, moderately reduced myocardial infarction, and did not affect mortality. Patients with acute ST-segment elevation myocardial infarction (STEMI) have an elevated risk of stroke, most of which are cardioembolic in origin because of left ventricular (LV) thrombus formation. Current guidelines recommend the use of vitamin K antagonist (VKA) for up to 3-6 months for treatment of left ventricular (LV) thrombus post-acute myocardial infarction (AMI). However, treatment with direct oral anticoagulants (DOACs) may be another treatment option. 5,6 Dr. Alcalai et al. from Israel aimed to assess the efficacy of apixaban vs. warfarin in treating LV thrombus after MI. Thirty-five patients were enrolled and the primary outcome was the presence and size of LV thrombus 3 months after initiation of anticoagulation. Thrombus completely resolved in 14 of 15 patients in the warfarin group and in 16 of 17 in the apixaban group. Two patients had major bleeding in the warfarin group while no major bleeding events were recorded in the apixaban group. The authors concluded that their small study suggested that apixaban is non-inferior to warfarin for treatment of patients with LV thrombus after acute MI. Mechanical prosthetic valve thrombosis (MPVT) is a serious and often fatal complication after heart valve replacement surgery. 7 Thrombolysis is an alternative to surgery for MPVT. Dr. De Caterina and co-workers has performed an open-label, pilot randomized clinical trial randomized adult patients (n = 120) with acute obstructive MPVT to an ultraslow thrombolytic regimen [25 mg of recombinant
Circulation Journal, 2013
Background: A limited number of studies have assessed the benefit and risk among the different antiplatelet and antithrombotic therapies in patient with stroke and peripheral artery disease (PAD). We compared the efficacy and safety of clopidogrel, cilostazol, warfarin, and aspirin. Methods and Results: A retrospective cohort study analyzing the Taiwan National Health Insurance Research Dataset identified patients with stroke and PAD from 2002 to 2008. Patients were stratified according to their use of aspirin, clopidogrel, cilostazol, warfarin or combination therapy. A total of 1,686 patients were enrolled: aspirin (n=862), clopidogrel (n=92), warfarin (n=136), cilostazol only (n=515), and cilostazol-based combination therapy (n=81). Compared with aspirin, cilostazol could reduce the risk of ischemic stroke [hazard ratio (HR) 0.79, 95% confidence interval (CI) 0.63-0.98, P=0.0349) and no increase in hemorrhagic events (HR 0.98, 95% CI 0.74-1.32, P=0.9122). Clopidogrel decreased the risk of ischemic stroke (HR 0.47, 95% CI 0.29-0.78, P=0.0033) and hemorrhagic events (HR 0.64, 95% CI 0.31-0.96, P=0.034) more than aspirin. There was no statistical difference regarding the risk of stroke and hemorrhagic events among warfarin, cilostazol-based combination therapy and aspirin. Conclusions: Cilostazol and clopidogrel were more effective in preventing recurrent ischemic stroke without increased hemorrhagic events than aspirin in patients with PAD.
Journal of Thoracic Oncology, 2009
Background: Patients with cancer, including lung cancer are at an increased risk for venous thromboembolism and frequently are anticoagulated. Due to concerns of bleeding and drug-drug interactions, many clinical trials suggest the use of low-molecular-weight heparin (LMWH) rather than warfarin (coumadin) for patients requiring anticoagulation. We sought to evaluate, in a retrospective analysis, whether these recommendations were appropriate. Material/Methods: A pooled analysis of three lung cancer trials conducted by the NCIC Clinical Trials Group was performed to evaluate the risk of bleeding in patients receiving warfarin or LMWH; concomitant usage of nonsteroidal antinflammatories or aspirin. The Mantel-Haentzel test stratified by treatment group was used to analyze the prevalence of bleeding (all and Նgrade 3) according to LMWH, warfarin or nonsteroidal antiinflammatory drugs usage. Logistic regression was used to adjust for baseline characteristics including age, sex, performance status, creatinine, platelets. Results: Although bleeding was reported in a quarter of patients, only 2% experienced severe bleeding, with rates similar across the trials. In univariate analyses the risk of bleeding seemed higher with LMWH or warfarin usage, history of bleeding, thrombocytopenia, and increased age. However, in adjusted analyses only warfarin use was a significant risk factor (p ϭ 0.073). Conclusions: In this retrospective analysis, warfarin seemed to increase the risk of bleeding in lung cancer patients enrolled in clinical trials. Current recommendations in many clinical trials to preferentially use LMWH seem appropriate.
Ever Decreasing Circles: Advances in Antiplatelet Therapy and Anticoagulation
Stroke, 2003
A spirin and anticoagulation with warfarin have been the mainstays of secondary stroke prevention. However, questions remain as to whether antiplatelet therapy or anticoagulation is superior and whether the two are synergistic in stroke prevention. This review highlights new advances in stroke prevention in 2002 using these agents. We conclude by exploring possible areas for future inquiry.
Combined Antiplatelet Therapy: Still a Sweeping Combination in Cardiology
Cardiovascular & Hematological Agents in Medicinal Chemistry, 2013
Platelets play a key role in the pathogenesis of atherothrombosis, involved in both the development and progression of atherosclerotic heart disease, and the attendant acute thrombotic complications. Antiplatelet therapy constitutes a mainstay therapy for patients with acute coronary syndromes and generally high-risk patients with atherothrombosis. Until recently, dual antiplatelet therapy (DAPT) for the treatment and prevention of the complications of atherothrombotic disease was traditionally limited to aspirin plus clopidogrel. However, a most important pertaining issue emerged, that of the occurrence of drug-resistance or tolerance observed in some patients for both these antithrombotic agents, which limited the efficacy and applicability of this combined therapy.The availability of the newer thienopyridine, prasugrel, and the cyclopentyl-triazolopyrimidine, ticagrelor, represents an important addition to the physician's armamentarium. Dual antiplatelet therapy with aspirin and clopidogrel or one of the newer agents interferes with platelet activation in complementary, but separate pathways. Aspirin irreversibly inhibits cyclooxygenase, thus preventing the production of thromboxane A 2 , which is a prothrombotic and vasoconstrictive substance. Thienopyridines (clopidogrel/prasugrel) irreversibly and ticagrelor reversibly prevent and inhibit platelet activation by blocking one of the three known adenosine 5'-diphosphate (ADP) receptors (the P2Y 12 receptor) on the platelet surface, thus interfering with platelet activation, degranulation and aggregation. Each of these antiplatelet agents has a protective effect against adverse vascular events; classical DAPT with aspirin and clopidogrel has an even stronger antiplatelet effect compared with either agent alone, however DAPT combining aspirin with one of the newer more potent agents translates into superior antithrombotic protection in atherothrobotic vascular disease, albeit at an increased, though not inordinately, risk for bleeding complications.