Ever Decreasing Circles: Advances in Antiplatelet Therapy and Anticoagulation (original) (raw)
Selection of anticoagulants or antiplatelet-aggregating agents for prevention of stroke
Current Neurology and Neuroscience Reports, 2002
Stroke is one of leading causes of mortality and morbidity in the United States. Stroke prevention includes treatment of the stroke risk factors and long-term use of antithrombotic agents. Various agents have been studied for stroke prevention and other trials are ongoing. The aim of this article is to provide an overview of the recent guidelines, recommendations, and clinical trial results using antithrombotic therapy for stroke prevention.
Antiplatelets in Stroke Prevention
Current Vascular Pharmacology, 2014
Stroke is the second cause of death worldwide and one of the leading causes of disability. Approximately 25% of strokes are recurrent. In patients who are at high risk because they already have occlusive vascular disease, long-term antiplatelet therapy (eg, with aspirin) reduces the yearly risk of serious vascular events (non-fatal myocardial infarction, non-fatal stroke, or vascular death) by about a quarter. Current recommendations for prevention of secondary stroke indicate for the broad use of antiplatelet therapy for the prevention of recurrent stroke in patients with a history of non-cardioembolic stroke or TIA. For primary prevention, however, the balance is less clear because the risks without aspirin, and hence the absolute benefi ts of aspirin, are generally an order of magnitude lower than in secondary prevention. In patients who are at high risk because they already have occlusive vascular disease, long-term antiplatelet therapy (e.g. with aspirin) reduces the yearly risk of serious vascular events (non-fatal myocardial infarction, non-fatal stroke, or vascular death) by about a quarter. Although several trials have investigated the use of antiplatelet drugs in ischemic stroke patients, ascertaining the sure benefit, especially in secondary prevention in non-cardioembolic stroke, various issues remains unclarified, and new questions arise with the analysis of the results of available trials.
Antiplatelet therapy in secondary stroke prevention
Expert Opinion on Pharmacotherapy, 2001
Stroke is the third leading cause of death in the United States. Antiplatelet agents are the mainstays of ischaemic stroke prevention. The therapies recommended for initial therapy include aspirin (50-325 mg) daily, the combination of aspirin (25 mg) and extended-release dipyridamole (200 mg) b.i.d., or clopidogrel (75 mg) daily. Ticlopidine 250 mg b.i.d. is approved for stroke prevention but is no longer a first-line therapy. This article reviews the literature on antiplatelet agents for secondary stroke prevention.
Dual or Mono Antiplatelet Therapy for the Prevention of Ischemic Stroke: A Literature Review
Cureus, 2018
Ischemic stroke is defined as a sudden loss of blood to the brain which results in deprivation of oxygen and other nutrients. It can be either a transient episode called as "transient ischemic attack" (TIA), or it could last longer than 24 hours giving rise to "infarction of tissues" in the central nervous system. Anti-platelet agents are widely used for the secondary prophylaxis of ischemic stroke, and amongst them, aspirin remains the drug of choice. In this literature review, we summarized the existing data regarding the ischemic type of strokes with particular attention to the use of antiplatelet agents for this purpose. The following review highlights the significance of the use of dual antiplatelet (aspirin and clopidogrel) regimen for the stroke prevention. The role of dual antiplatelet (aspirin and clopidogrel) in patients with a recent TIA (within 30 days) or severe stenosis (70%-99%) of a major intracranial artery, for 90 days, might be a beneficial app...
Recent Clinical Trial Results with Antiplatelet Therapy: Implications in Stroke Prevention
Cerebrovascular Diseases, 2004
Dual antiplatelet therapy that inhibits more than one pathway of platelet activation is appealing and biologically rational. The CURE study evaluated the efficacy and safety of clopidogrel on top of acetylsalicylic acid (ASA) versus standard therapy (including ASA) in over 12,000 patients with unstable angina or non-ST-segment elevation myocardial infarction (MI). Clopidogrel in combination with ASA reduced the relative risk of the combined atherothrombotic endpoint of cardiovascular death, MI or stroke by 20% (95% CI 0.72–0.90; p < 0.001) and the absolute risk of this composite endpoint by 2.1%. While the study was not powered or designed to demonstrate a reduction in stroke, there was a 14% reduction in stroke risk (p > 0.05). Dual antiplatelet therapy was associated with an acceptable 1% increase in the incidence of major bleeding events (p = 0.001). PCI-CURE, a prespecified substudy of patients who underwent percutaneous coronary intervention (PCI) during CURE, confirmed t...
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.
Comparison of antiplatelet regimens in secondary stroke prevention: a nationwide cohort study
BMC Neurology, 2015
Background: In patients with ischemic stroke of non-cardioembolic origin, acetylsalicylic acid, clopidogrel, or a combination of acetylsalicylic acid and dipyridamole are recommended for the prevention of a recurrent stroke. The purpose of this study was to examine the risk of bleeding or recurrent stroke associated with these three treatments. Methods: Patients who were discharged with first-time ischemic stroke from 2007-2010, with no history of atrial fibrillation were identified from Danish nationwide registries. Hazard ratios (HRs) and 1-year risks of recurrent ischemic stroke and bleeding were calculated for each antiplatelet regimen. Results: Among patients discharged after first-time ischemic stroke, 3043 patients were treated with acetylsalicylic acid, 12,295 with a combination of acetylsalicylic acid and dipyridamole, and 3885 with clopidogrel. Adjusted HRs for clopidogrel versus the combination of acetylsalicylic acid and dipyridamole were 1.02 (95 % confidence interval [CI]: 0.89-1.17) for ischemic stroke and 1.06 (95 % CI: 0.83-1.35) for bleeding. Adjusted HRs for acetylsalicylic acid versus the combination of acetylsalicylic acid and dipyridamole were 1.48 (95 % CI: 1.31-1.67) for stroke and 1.47 (95 % CI: 1.18-1.82) for bleeding. Clopidogrel versus acetylsalicylic acid yielded HRs of 0.69 (95 % CI: 0.59-0.81) and 0.72 (95 % CI: 0.55-0.96) for stroke and bleeding, respectively. The 1-year predicted risks associated with acetylsalicylic acid, the combination of acetylsalicylic acid and dipyridamole, and clopidogrel were 11.1 (95 %
Dual Antiplatelet Therapy Role in Acute Ischemic Stroke
Journal of Critical Care & Emergency Medicine
Stroke is the second greatest cause of mortality and one of the top causes of long-term disability. The fatality rate and age-adjusted prevalence of stroke have decreased globally over the past quarter-century. However, the absolute number of stroke cases has climbed, as populations have grown older. Initiating antiplatelet medications early in patients with acute ischemic stroke (AIS) is essential for preventing stroke recurrence. Aspirin, clopidogrel, and dipyridamole are the most commonly used antiplatelet medications worldwide. Combining antiplatelet drugs is associated with an increased risk of bleeding when used for long-term prophylaxis. The use of Dual antiplatelet treatment (DAPT) for a shorter duration is associated with a lower risk than long-term usage. The best period of treatment for transient ischemic attack (TIA) and mild ischemic stroke appears to be between 21 and 30 days.
Newer Oral Anticoagulants: Stroke Prevention and Pitfalls
The open cardiovascular medicine journal, 2016
Warfarin is very effective in preventing stroke in patients with atrial fibrillation. However, its use is limited due to fear of hemorrhagic complications, unpredictable anticoagulant effects related to multiple drug interactions and dietary restrictions, a narrow therapeutic window, frequent difficulty maintaining the anticoagulant effect within a narrow therapeutic window, and the need for inconvenient monitoring. Several newer oral anticoagulants have been approved for primary and secondary prevention of stroke in patients with non-valvular atrial fibrillation. These agents have several advantages relative to warfarin therapy. As a group, these direct oral anticoagulants (DOAC), which include the direct thrombin inhibitor, dabigatran, and the factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban), are more effective than dose adjusted warfarin for prevention of all-cause stroke (including both ischemic and hemorrhagic stroke), and have an overall more favorable safety profile...
Trends in Usage of Alternative Antiplatelet Therapy After Stroke and Transient Ischemic Attack
Stroke, 2008
The effects of alternative antiplatelet agents such as clopidogrel and dipyridamole have been studied in clinical trials and heavily marketed. Because public data on their usage are limited, we examined trends in their prescription after stroke and transient ischemic attack to assess the impact of marketing and trial results. Between 2001 and 2005, 85 US hospitals prospectively enrolled all patients admitted with ischemic stroke or transient ischemic attack into a registry designed for quality improvement (Ethos). Data on rates of antiplatelet medication usage at discharge were examined over time, and trends were evaluated by the Mantel-Haenszel test. Among 18 020 patients included during the 4-year period, 89% were discharged on antithrombotic medication. Between the first quarter of 2001 and the first quarter of 2004, prescription of clopidogrel-aspirin doubled (P<0.0001 for trend), coincident with publication of results from CURE and CREDO showing efficacy in patients with acute coronary syndromes. Monotherapy with aspirin or clopidogrel decreased concomitantly, and use of dipyridamole-aspirin remained constant. After an increased bleeding risk was reported in the clopidogrel-aspirin arm of the MATCH trial, use of the combination decreased sharply from 31.5% in the first quarter of 2004 to 12.8% in the first quarter of 2005 (P<0.0001), while an increase was seen in the use of clopidogrel alone (7.6% to 12.8%, P=0.03) and dipyridamole-aspirin (7.4% to 20.2%, P<0.0001). Clopidogrel and dipyridamole-aspirin are used frequently after stroke or transient ischemic attack. Use of clopidogrel-aspirin was common in patients with recent ischemic stroke before the publication of MATCH, after which rates dramatically declined and use of dipyridamole-aspirin and clopidogrel alone increased.
PloS one, 2008
Aspirin, dipyridamole and clopidogrel are effective in secondary vascular prevention. Combination therapy with three antiplatelet agents might maximise the benefit of antiplatelet treatment in the secondary prevention of ischaemic stroke. A randomised, parallel group, observer-blinded phase II trial compared the combination of aspirin, clopidogrel and dipyridamole with aspirin alone. Adult patients with ischaemic stroke or transient ischaemic attack (TIA) within 5 years were included. The primary outcome was tolerability to treatment assessed as the number of patients completing randomised treatment. Recruitment was halted prematurely after publication of the ESPRIT trial (which confirmed that combined aspirin and dipyridamole is more effective than aspirin alone). 17 patients were enrolled: male 12 (71%), mean age 62 (SD 13) years, lacunar stroke syndrome 12 (71%), median stroke/TIA onset to randomisation 8 months. Treatment was discontinued in 4 of 9 (44%) patients receiving tripl...
Recent advances in preventing stroke recurrence
F1000Research, 2017
Recent advances in secondary stroke prevention include new evidence in hypertension, nutrition, anticoagulation, antiplatelet therapy, intracranial stenosis, percutaneous closure of patent foramen ovale, and lipid-lowering therapy. Individualized therapy for hypertension based on phenotyping with plasma renin and aldosterone markedly improves blood pressure control in patients with resistant hypertension. A Mediterranean diet can reduce the risk of stroke by nearly half. The diagnosis and treatment of metabolic vitamin B12 deficiency, and B vitamins to lower homocysteine, can reduce the risk of stroke by approximately 30%. There are problems with clopidogrel that can be overcome by using ticagrelor, and new anticoagulant drugs markedly improve anticoagulation for stroke prevention, particularly in atrial fibrillation. There are pharmacokinetic problems with dabigatran that deserve attention. Intensive medical therapy is better than stenting for intracranial stenosis, and new therapi...
Secondary prevention of ischemic stroke: Challenging patient scenarios
Journal of Hospital Medicine, 2008
The risk for recurrent stroke following a stroke or transient ischemic attack (TIA) is high. Prevention of a secondary event is a priority, as the associated morbidity and mortality are great. Antiplatelet agents have been shown to reduce this risk, but the choice of treatment modality depends on a number of factors, including the underlying cause of the stroke and the patient's comorbidities. For example, a cardioembolic stroke is best treated with anticoagulants, whereas one of noncardioembolic origin requires antiplatelet therapy. A number of challenging patient scenarios are explored in this article, and appropriate medical management is discussed, with the goal of examining the most recent trial data and information in the context of an actual case. Eight sample cases are presented: stroke prevention in a patient with recent stent placement, low ejection fraction, intracranial stenosis, carotid stenosis, atherosclerosis of the aortic arch, symptomatic coronary artery disease, antiplatelet failure, and stroke prevention in a patient already on warfarin. Journal of Hospital Medicine 2008;3(4 Suppl):S20–S28. © 2008 Society of Hospital Medicine.
Triple antiplatelet therapy for secondary prevention of recurrent ischemic stroke
Antiplatelet agents are effective for secondary prevention after ischemic stroke, although they do not always prevent recurrent events. Laboratory studies confirm that therapy with 3 antiplatelet agents is superior to dual therapy or monotherapy at inhibiting platelet and leucocyte function. We report here a 69-year-old man who had recurrent strokes despite single or dual antiplatelet agents, but who responded to a combination of aspirin, dipyridamole, and clopidogrel. Likewise, triple antiplatelet therapy was effective in a series of 8 additional patients during a period of 28 months of follow up. Because combining 3 agents runs the risk of major bleeding, clinical trials are essential to address issues of safety and efficacy in patients with stroke. Key Words: Antiplatelet therapy-ischemic stroke-secondary stroke prevention.