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

Jane G. Morris, MD

Emily L Carter, MD

Stephen A. Martin, MD, EdM

A multifactorial approach is key to effective secondary stroke prevention. Here’s how to individualize your plan for your at-risk patients.

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PRACTICE RECOMMENDATIONS

› Encourage lifestyle modifications, including smoking cessation, alcohol moderation, appropriate diet, and exercise to reduce the risk of recurrent stroke. A

› Optimize blood pressure control using an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker and a thiazide diuretic. A

› Only use beta-blockers if there is another indication for them. A

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

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

References

1. Hackam DG, Spence JD. Combining multiple approaches for the secondary prevention of vascular events after stroke: a quantitative modeling study. Stroke. 2007;38:1881-1885.

2. Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 Suppl 2):S76-S99.

3. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:2160-2236.

4. Rashid P, Leonardi-Bee J, Bath P. Blood pressure reduction and secondary prevention of stroke and other vascular events: a systematic review. Stroke. 2003;34:2741-2748.

5. Amarenco P, Bogousslavsky J, Callahan A, et al, for the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355:549-559.

6. Benavente OR, Hart RG, McClure LA, et al, for the SPS3 Investigators. Effects of clopidogrel added to aspirin in patients with recent lacunar stroke. N Engl J Med. 2012;367:817-825.

7. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996;348:1329-1339.

8. Sacco RL, Diener HC, Yusuf S, et al. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. N Engl J Med. 2008;359:1238-1251.

9. Diethrich EB, N’diaye M, Reid DB. The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST): implications for clinical practice. In: Henry M, Diethrich EB, Polydorou A, eds. The Carotid and Supra-Aortic Trunks: Diagnosis, Angioplasty and Stenting. 2nd ed. Oxford, UK: Wiley-Blackwell; 2011.

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.

11. SPS3 Study Group. Blood pressure targets in patients with recent lacunar stroke: the SPS3 randomised trial. Lancet. 2013;382:507-515.

12. Carroll JD, Saver JL, Thaler DE, et al. Closure of patent foramen ovale versus medical therapy after cryptogenic stroke. N Engl J Med. 2013;368:1092-1100.

13. 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.

14. Romero JR, Morris J, Pikula A. Stroke prevention: modifying risk factors. Ther Adv Cardiovasc Dis. 2008;2:287-303.

15. Hankey GJ. Smoking and risk of stroke. J Cardiovasc Risk. 1999;6:207-211.

16. Shah RS, Cole JW. Smoking and stroke: the more you smoke the more you stroke. Expert Rev Cardiovasc Ther. 2010;8:917-932.

17. Bhat VM, Cole JW, Sorkin JD, et al. Dose-response relationship between cigarette smoking and risk of ischemic stroke in young women. Stroke. 2008;39:2439-2443.

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.

20. Davis SM, Donnan GA. Clinical practice. Secondary prevention after ischemic stroke or transient ischemic attack. N Engl J Med. 2012;366:1914-1922.

21. Jauch EC, Saver JL, Adams HP, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013;44:870-947.

22. Magid DJ, Green BB. Home blood pressure monitoring: take it to the bank. JAMA. 2013;310:40-41.

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.

27. The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet. 1997;349:1569-1581.

28. CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group. Lancet. 1997;349:1641-1649.

29. CADISS trial investigators, Markus HS, Hayter E, et al. Antiplatelet treatment compared with anticoagulation treatment for cervical artery dissection (CADISS): a randomised trial. Lancet Neurol. 2015;14:361-367.

30. Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke. EAFT (European Atrial Fibrillation Trial) Study Group. Lancet. 1993;342:1255-1262.

31. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22:983-988.

32. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Int Med. 2007;146:857-867.

33. Hart RG, Tonarelli SB, Pearce LA. Avoiding central nervous system bleeding during antithrombotic therapy. Recent data and ideas. Stroke. 2005;36:1588-1593.

34. Pisters R, Lane DA, Nieuwlaat R, et al. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: The Euro Heart Survey. Chest. 2010;138:1093-1100.

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.

36. Gorman EW, Perkel D, Dennis D, et al. Validation of the HAS-BLED tool in atrial fibrillation patients receiving rivaroxaban. J Atr Fibrillation. 2016;9:1461.

37. Gage BF, Birman-Deych E, Kerzner R, et al. Incidence of intracranial hemorrhage in patients with atrial fibrillation who are prone to fall. Am J Med. 2005;118:612-617.

38. US Food and Drug Administration. FDA approves Praxbind, the first reversal agent for the anticoagulant Pradaxa. October 16, 2015. Available at: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm467300.htm. Accessed May 26, 2017.

39. Paciaroni M, Agnelli G, Falocci N, et al. Early recurrence and cerebral bleeding in patients with acute ischemic stroke and atrial fibrillation: effect of anticoagulation and its timing: the RAF Study. Stroke. 2015;46:2175-2182.

40. Sandercock PA, Counsell C, Kane EJ. Anticoagulants for acute ischaemic stroke. Cochrane Database Syst Rev. 2015;3:CD000024.

41. Bath PM, Lindenstrom E, Boysen G, et al. Tinzaparin in acute ischaemic stroke (TAIST): a randomised aspirin-controlled trial. Lancet. 2001;358:702-710.

42. Berge E, Abdelnoor M, Nakstad PH, et al. Low molecular-weight heparin versus aspirin in patients with acute ischaemic stroke and atrial fibrillation: a double-blind randomised study. HAEST Study Group. Heparin in Acute Embolic Stroke Trial. Lancet. 2000;355:1205-1210.

43. Sherman DG, Albers GW, Bladin C, et al. The efficacy and safety of enoxaparin versus unfractionated heparin for the prevention of venous thromboembolism after acute ischaemic stroke (PREVAIL Study): an open-label randomised comparison. Lancet. 2007;369:1347-1355.

44. Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545-2559.

45. Kernan WN, Viscoli CM, Furie KL, et al. Pioglitazone after ischemic stroke or transient ischemic attack. N Engl J Med. 2016;374:1321-1331.

46. Meier B, Kalesan B, Mattle HP, et al. Percutaneous closure of patent foramen ovale in cryptogenic embolism. N Engl J Med. 2013;368:1083-1091.

47. Furlan AJ, Reisman M, Massaro J, et al. Closure or medical therapy for cryptogenic stroke with patent foramen ovale. N Engl J Med. 2012;366:991-999.

Patients who suffer a stroke rarely have just one vascular risk factor. Therefore, the approach to secondary stroke prevention must be multifactorial. In fact, it has been estimated that 80% of recurrent strokes could be prevented through the application of a comprehensive, multifactorial approach that includes lifestyle modification and optimal medical management.¹ Such an achievement would save millions of people from disability and functional decline, as well as millions of dollars in related medical costs.

The initial approach to patients with stroke is focused on stabilization and a rapid work-up to identify the most likely etiology. Common causes of stroke include large artery atherosclerosis, cardiac emboli, and small vessel disease; less common causes include dissection, aortic emboli, and non-atherosclerotic vascular disease. If a complete diagnostic work-up is unrevealing, the stroke is said to be cryptogenic. Determining the correct etiology of a stroke is paramount to preventing secondary stroke (FIGURE^2-13).

Effective secondary prevention strategies designed to prevent a stroke or transient ischemic attack (TIA) in a patient with a known history of either event include lifestyle modifications, medications, and when appropriate, mechanical interventions. As a primary care physician (PCP), you are uniquely positioned to spearhead the prevention of secondary strokes: Not only are you at the forefront of prevention and the use of techniques such as motivational interviewing, but you also have longstanding relationships with many of your patients. In fact, the success of many interventions is improved by the informed, enduring, and trusting nature of relationships between patients and their PCPs.

In the first part of this 2-part series, we focused on subacute stroke management and outlined the recommended work-up for subacute stroke/TIA (see “Stroke: A road map to subacute management,” 2017;66:366-374). In this part, we focus on secondary prevention. The more common modifiable conditions encountered in primary care are discussed here, while many of the more rare etiologies (hypercoagulable states, sickle cell disease, and vasculitis) are outside the scope of this article.

Lifestyle interventions: Target tobacco use, obesity, alcohol intake

Lifestyle modifications can have a positive impact on many of America’s most prevalent diseases, and stroke is no exception.¹⁴ Many of the disease states identified as risk factors for stroke (type 2 diabetes, hypertension, dyslipidemia) are exacerbated by tobacco use, obesity, and excessive alcohol intake.

Does your patient smoke? Up to 25% of all strokes are directly attributable to cigarette smoking.¹⁵ Smoking raises an individual’s risk for stroke in a dose-dependent fashion.^15,16One study demonstrated that, compared to never-smokers, women ages 15 to 49 years who smoked a half-pack per day had an odds ratio for ischemic stroke of 2.2; those who smoked 2 packs per day had an odds ratio of 9.1.¹⁷ After cessation, stroke risk generally returns to baseline within 5 years.¹⁶ Thus, smoking cessation is among the most significant steps a patient can take to reduce the risk of both primary and secondary stroke.

Is your patient overweight? While obesity in and of itself is a risk factor for stroke, a focus on nutrition and physical activity as mechanisms for weight loss is far superior to focusing on either element alone. Physical activity—consisting of at least 40 minutes of moderate intensity aerobic exercise 3 to 4 times per week—and a diet that emphasizes fruits and vegetables, whole grains, and healthy fats, have both independently demonstrated benefits in secondary stroke prevention and are important parts of American College of Cardiology (ACC)/American Heart Association (AHA) guidelines.^2,3

It’s estimated that 80% of recurrent strokes could be prevented through the application of a comprehensive, multifactorial approach that includes optimal medical management.

The Mediterranean Diet, which emphasizes consumption of fruits and vegetables, legumes, tree nuts, olive oil, and lean protein, has long been associated with cardiovascular benefit.¹⁸ One prospective, randomized, single-blinded trial involving approximately 600 patients that looked at secondary prevention of coronary heart disease found that following the diet significantly reduced mortality compared with a usual prudent post-infarct diet (number needed to treat [NNT]=30 over 4 years).¹⁹

Is alcohol consumption an issue? Chronic heavy alcohol intake contributes to the development of hemorrhagic and ischemic stroke through multiple mechanisms, including alcohol-induced hypertension, alcoholic cardiomyopathy, and atrial fibrillation (AF). Light or moderate alcohol consumption has a paradoxical mild protective effect on ischemic stroke, thought to possibly be mediated by an increase in high-density lipoprotein (HDL) level and mild antiplatelet effect.³

AHA/American Stroke Association (ASA) guidelines indicate that no more than one standard drink per day for women and 2 drinks per day for men is reasonable.³Counsel patients who drink in excess of this about the benefits of decreasing alcohol intake or abstaining altogether.