Stroke: Secondary prevention of ischemic events

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Applied Evidence

Stroke: Secondary prevention of ischemic events

J Fam Pract. 2017 July;66(7):420-422,424-427

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From The Journal of Family Practice | 2017;66(7):420-422,424-427.

References

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10. Brott TG, Halperin JL, Abbara S, et al. 2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS guideline on the management of patients with extracranial carotid and vertebral artery disease: executive summary. Circulation. 2011;124:489-532.

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18. Lakkur S, Judd SE. Diet and stroke: recent evidence supporting a Mediterranean-style diet and food in the primary prevention of stroke. Stroke. 2015;46:2007-2011.

19. de Lorgeril M, Salen P, Martin JL, et al. Mediterranean dietary pattern in a randomized trial: prolonged survival and possible reduced cancer rate. Arch Intern Med. 1998;158:1181-1187.

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23. Diener H-C, 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, placebo-controlled trial. Lancet (London, England). 2004;364:331-337.

24. Bhatt DL, Fox KAA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006;354:1706-1717.

25. Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med. 2011;365:993-1003.

26. Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013;369:11-19.

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35. Quinn GR, Singer DE, Chang Y, et al. How well do stroke risk scores predict hemorrhage in patients with atrial fibrillation? Am J Cardiol. 2016;118:697-699.

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Is an anticoagulant in order? Which agent, when

The most common cause of cardioembolic stroke is AF, which accounts for at least 15% of ischemic strokes, a number that rises in those over the age of 80.^20,30,31 A meta-analysis of more than 28,000 patients with non-valvular AF demonstrated that warfarin reduced the risk of stroke by 64%.³²

All ischemic stroke patients who do not have an indication for oral anticoagulation should be placed on long-term daily aspirin.

The rate of intracerebral hemorrhages during oral anticoagulation ranges from 0.3% to 0.6% per year.³³ The risk of bleeding complications can be mitigated by keeping international normalized ratios ≤3.0, maintaining good BP control, and avoiding concurrent use of antiplatelets in the absence of a clear indication for them.³³

Several risk assessment scores, such as the HAS-BLED,³⁴ can help with estimating the risk of hemorrhagic complications, although these scores have their limitations.^35,36 Even in an older population (mean age 83 years) with a high risk for falls, warfarin provided a net benefit in a composite endpoint of out-of-hospital death or hospitalization for stroke, MI, or hemorrhage in a retrospective study of over 1200 Medicare beneficiaries.³⁷

AF is not the only cause of cardioembolic stroke to consider. Additional high-risk factors warranting anticoagulation include rheumatic mitral valve disease, the presence of mechanical aortic or mitral valves, known mural thrombus, and acute anterior ST segment elevation myocardial infarctions (STEMIs) with resulting anterior apical dyskinesis/akinesis and concurrent ischemic stroke/TIA.³(The specific management of each of these situations is beyond the scope of this paper.)

The choice of anticoagulation agent is based on multiple factors, including cost, risk of non-reversible bleeding, drug interactions, renal function, and patient preference. Approved options currently include warfarin/vitamin K antagonist therapy, apixaban, rivaroxaban, dabigatran and edoxaban.³ Choice of therapy will continue to evolve as reversal agents, such as idarucizumab, are developed. Idarucizumab, a reversal agent for dabigatran, received approval from the US Food and Drug Administration in October 2015.³⁸

When to start anticoagulation. There are limited data regarding the optimal timing of initiation of anticoagulation following a stroke; however, a recent multicenter prospective study supported the common practice of initiating anticoagulation therapy within 4 to 14 days of the event.³⁹Individual patient factors must be taken into consideration, including the size of the stroke (the larger the stroke, the higher the risk for hemorrhagic transformation), BP control, any additional risk factors for bleeding, and the estimated risk of early recurrent stroke.

Bridging patients onto anticoagulation with unfractionated or low-molecular-weight heparin in the setting of acute stroke is not recommended.⁴⁰ Results from randomized controlled trials involving unfractionated heparin, heparinoids, and low-molecular-weight heparin have not reported any benefit to these agents over aspirin at preventing early stroke recurrence.^27,41,42

For immobile or hospitalized patients. Subcutaneous heparin for the prevention of deep vein thrombosis (DVT) during immobility and hospitalization is recommended.⁴³ Patients who cannot tolerate anticoagulation should be maintained on low-dose antiplatelet therapy. Experts do not recommend dual treatment with aspirin and anticoagulation in most cases. However, recent coronary artery stent placement does require temporary dual treatment, with duration dependent on the type of stent placed.

A role for glycemic control? Still to be determined

The specific role of diabetic management in secondary stroke prevention remains unclear. The 2008 ACCORD trial,⁴⁴ a randomized study involving over 10,000 patients with a median glycated hemoglobin level of 8.1%, investigated intensive hyperglycemic control (targeting a glycated hemoglobin level <6.0% vs <7.9%) as a means of decreasing cardiovascular risk. However, the trial ended 17 months early because of an increase in all-cause mortality in the intensive treatment arm compared with the standard management group. The same trial was also unable to demonstrate a decrease in stroke risk with a decrease in A1c.⁴⁴

More recently, the IRIS (Insulin Resistance Intervention after Stroke) trial⁴⁵ (2016) found a 2.8% absolute risk reduction in stroke or MI among participants who had a stroke or TIA in the previous 6 months who were treated with pioglitazone vs placebo over 4.8 years (NNT=36). Participants were required to have insulin resistance, but were excluded if they had diabetes. The authors did, however, report a notable increase in the risk of bone fractures requiring surgery or hospitalization in the pioglitazone arm (5.1% vs 3.2%; number needed to harm [NNH]=53).

Treat patients with stroke or TIA presumed to be of atherosclerotic origin with high-intensity statin therapy, regardless of low-density lipoprotein level.

The impact this single study should have on standard secondary prevention is not yet clear. The authors concluded, “It seems reasonable to consider individual treatment preference and risk of drug-related adverse events in addition to potential benefits when making patient-specific decisions regarding therapy.”⁴⁵