Pharmacotherapy for the Secondary Prevention of Stroke
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Stroke recurrence continues to be the major risk for stroke survivors. Risk factor control and antithrombotic medication are two major strategies for patients with a prior stroke or transient ischaemic attack (TIA) to prevent stroke recurrence.
Hypertension, dyslipidaemia and diabetes mellitus are risk factors that are modifiable by pharmacotherapy, as well as by lifestyle modification. Antihypertensive treatment is recommended for secondary stroke prevention for both hypertensive and normotensive patients. HMG-CoA reductase inhibitor (statin) therapy to obtain an intensive lipid-lowering effect is also highly recommended. A recent trial indicated that treatment with pioglitazone is effective for patients with type 2 diabetes. However, the evidence for risk factor control is relatively new, and further studies are needed for better evidence-based prevention.
For patients with noncardioembolic ischaemic stroke or TIA, antiplatelet therapy rather than anticoagulation is recommended to reduce the risk of recurrent stroke and other cardiovascular events. Aspirin was the first antiplatelet agent to have established evidence for secondary stroke prevention. Currently, aspirin monotherapy, the combination of aspirin and extendedrelease dipyridamole, and clopidogrel monotherapy are recommended as the major choices. The combination of aspirin and clopidogrel is not routinely recommended. Adjusted-dose warfarin with a target international normalized ratio range between 2.0 and 3.0 is recommended after an ischaemic stroke or TIA associated with nonvalvular atrial fibrillation. Bleeding complications are a critical problem with antithrombotic therapy. Warfarin, as well as antiplatelet therapy, increases the incidence of bleeding and worsens the severity of the bleeding events. Choosing antithrombotic agents and their intensity (dosage) appropriate to the stroke mechanism and the patient’s condition are essential for secondary stroke prevention.
KeywordsInternational Normalize Ratio Antiplatelet Agent Cilostazol Recurrent Stroke Antithrombotic Therapy
This article was partially supported by a Grant-in-Aid (H20-Junkanki-Ippan-019) from the Ministry of Health, Labour and Welfare, Japan, and a Grant-in-Aid for Scientific Research (Kiban C, #20591039) from the Japan Society for the Promotion of Science. The author has no conflicts of interest that are directly relevant to the content of this review.
- 1.Rundek T, Sacco RL. Outcome following stroke. In: Mohr JP, Choi DW, Grotta JC, et al., editors. Stroke: pathophysiology, diagnosis, and management. 4th ed. Philadelphia (PA): Churchill Livingstone, 2004: 35–57Google Scholar
- 13.Sacco RL, Adams R, Albers G, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke. Co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline. Stroke 2006 Feb; 37(2): 577–617Google Scholar
- 20.Goldstein LB, Adams R, Alberts MJ, et al. Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council. Co-sponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: the American Academy of Neurology affirms the value of this guideline. Stroke 2006 Jun; 37(6): 1583–633Google Scholar
- 28.Mancia G, De Backer G, Dominiczak A, et al. 2007 Guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2007 Jun; 25(6): 1105–87PubMedCrossRefGoogle Scholar
- 44.Costa J, Ferro JM, Matias-Guiu J, et al. Triflusal for preventing serious vascular events in people at high risk. Cochrane Database Syst Rev 2005 Jul 20; (3): CD004296Google Scholar
- 47.Markus HS, Droste DW, Kaps M, et al. Dual antiplatelet therapy with clopidogrel and aspirin in symptomatic carotid stenosis evaluated using Doppler embolic signal detection: the Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis (CARESS) trial. Circulation 2005 May 3; 111(17): 2233–40PubMedCrossRefGoogle Scholar
- 48.Diener HC, Bogousslavsky J, Brass LM, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebocontrolled trial. Lancet 2004 Jul 24–30; 364(9431): 331–7PubMedCrossRefGoogle Scholar
- 51.Stroke Prevention in Atrial Fibrillation Investigators. Adjusteddose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial. Lancet 1996 Sep 7; 348(9028): 633–8CrossRefGoogle Scholar
- 52.EAFT (European Atrial Fibrillation Trial) Study Group. Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke. Lancet 1993 Nov 20; 342(8882): 1255–62Google Scholar
- 53.Fuster V, Rydén LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) — developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006 Aug 15; 114(7): e257–354PubMedCrossRefGoogle Scholar
- 54.Yamaguchi T, for Japanese Nonvalvular Atrial Fibrillation-Embolism Secondary Prevention Cooperative Study Group. Optimal intensity of warfarin therapy for secondary prevention of stroke in patients with nonvalvular atrial fibrillation: a multicenter, prospective, randomized trial. Stroke 2000 Apr; 31(4): 817–21PubMedCrossRefGoogle Scholar
- 58.Algra A, De Schryver EL, van Gijn J, et al. Oral anticoagulants versus antiplatelet therapy for preventing further vascular events after transient ischaemic attack or minor stroke of presumed arterial origin. Cochrane Database Syst Rev 2006 Jul 19; (3): CD001342Google Scholar
- 60.Kase CS, Mohr JP, Caplan LR. Intracerebral hemorrhage. In: Mohr JP, Choi DW, Grotta JC, et al., editors. Stroke: pathophysiology, diagnosis, and management, 4th ed. Philadelphia (PA): Churchill Livingstone, 2004: 327–76Google Scholar
- 70.Fiore LD, Ezekowitz MD, Brophy MT, et al. Department of Veterans Affairs Cooperative Studies Program Clinical Trial comparing combined warfarin and aspirin with aspirin alone in survivors of acute myocardial infarction: primary results of the CHAMP study. Circulation 2002 Feb 5; 105(5): 557–63PubMedCrossRefGoogle Scholar
- 75.ACTIVE Writing Group on behalf of the ACTIVE Investigators. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 2006 Jun 10; 367(9526): 1903–12CrossRefGoogle Scholar