Abstract
Secondary stroke prevention in the elderly in many cases requires the use of drug therapy to maximize risk factor control. However, the elderly (≥65 years) are most likely to receive care that is not evidence-based, because of concerns for adverse events. In this review, we provide evidence to the practitioner in support of the value of blood pressure control with drug therapy to decrease recurrent stroke risk. This review also highlights evidence for the importance of statin therapy in stroke prevention among the elderly. Finally, the appropriate use of antiplatelet therapy and oral anticoagulation is addressed.
Similar content being viewed by others
References
Go AS, et al. Heart disease and stroke statistics—2014 update: a report from the American Heart Association. Circulation. 2014;129(3):e28–292.
Feng W, Hendry RM, Adams RJ. Risk of recurrent stroke, myocardial infarction, or death in hospitalized stroke patients. Neurology. 2010;74(7):588–93.
Judd SE, et al. Self-report of stroke, transient ischemic attack, or stroke symptoms and risk of future stroke in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study. Stroke. 2013;44(1):55–60.
National Heart, Lung, and Blood Institute. Morbidity and Mortality: 2012 Chart Book on Cardiovascular, Lung and Blood Diseases. Bethesda: National Institutes of Health; 2012.
Centers for Disease, C. and Prevention. Prevalence of stroke—United States, 2006–2010. Morb Mortal Wkly Rep. 2012;61(20):379–82.
Petrea RE, et al. Gender differences in stroke incidence and poststroke disability in the Framingham heart study. Stroke. 2009;40(4):1032–7.
Howard VJ, et al. Disparities in stroke incidence contributing to disparities in stroke mortality. Ann Neurol. 2011;69(4):619–27.
Kissela BM, et al. Age at stroke: temporal trends in stroke incidence in a large, biracial population. Neurology. 2012;79(17):1781–7.
Casper ML, Nwaise IA, Croft JB, Nilasena DS. Atlas of stroke hospitalizations among medicare beneficiaries. Atlanta: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2008.
Forti P, et al. Independent predictors of ischemic stroke in the elderly: prospective data from a stroke unit. Neurology. 2013;80(1):29–38.
Saposnik G, Black S, G. Stroke Outcome Research Canada Working. Stroke in the very elderly: hospital care, case fatality and disposition. Cerebrovasc Dis. 2009;27(6):537–43.
Kammersgaard LP, et al. Short- and long-term prognosis for very old stroke patients. The Copenhagen Stroke Study. Age Ageing. 2004;33(2):149–54.
Ovbiagele B, et al. Forecasting the future of stroke in the United States: a policy statement from the American Heart Association and American Stroke Association. Stroke. 2013;44(8):2361–75.
Howard G, Goff DC. Population shifts and the future of stroke: forecasts of the future burden of stroke. Ann N Y Acad Sci. 2012;1268:14–20.
Palnum KD, et al. Older patients with acute stroke in Denmark: quality of care and short-term mortality. A nationwide follow-up study. Age Ageing. 2008;37(1):90–5.
Lichtman JH, et al. Use of antithrombotic medications among elderly ischemic stroke patients. Circ Cardiovasc Qual Outcomes. 2011;4(1):30–8.
World Health Organisation. The World Health Report 2002: reducing risks, promoting healthy life. Geneva: World Health Organisation; 2002.
Burt VL, et al. Prevalence of hypertension in the US adult population. Results from the Third National Health and Nutrition Examination Survey, 1988–1991. Hypertension. 1995;25(3):305–13.
Julius S, et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet. 2004;363(9426):2022–31.
Messerli FH, et al. Dogma disputed: can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous? Ann Intern Med. 2006;144(12):884–93.
Sleight P, et al. Prognostic value of blood pressure in patients with high vascular risk in the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial study. J Hypertens. 2009;27(7):1360–9.
Bangalore S, et al. J-curve revisited: an analysis of blood pressure and cardiovascular events in the Treating to New Targets (TNT) trial. Eur Heart J. 2010;31(23):2897–908.
Staessen JA, et al. Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials. Lancet. 2000;355(9207):865–72.
Redon J, et al. Safety and efficacy of low blood pressures among patients with diabetes: subgroup analyses from the ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial). J Am Coll Cardiol. 2012;59(1):74–83.
Howard G, et al. Racial differences in the impact of elevated systolic blood pressure on stroke risk. JAMA Intern Med. 2013;173(1):46–51.
Lawes CM, et al. Blood pressure and stroke: an overview of published reviews. Stroke. 2004;35(4):1024.
White CL, et al. Blood pressure after recent stroke: baseline findings from the secondary prevention of small subcortical strokes trial. Am J Hypertens. 2013;26(9):1114–22.
Chalmers J, MacMahon S. Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS): interpretation and implementation. J Hypertens Suppl. 2003;21(5):S9–14.
Group PC. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet. 2001;358(9287):1033–41.
Kernan WN, 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(7):2160–236.
Group PC, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1575–85.
James PA, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507–20.
Group JS. Principal results of the Japanese trial to assess optimal systolic blood pressure in elderly hypertensive patients (JATOS). Hypertens Res. 2008;31(12):2115–27.
Ogihara T, et al. Target blood pressure for treatment of isolated systolic hypertension in the elderly: valsartan in elderly isolated systolic hypertension study. Hypertension. 2010;56(2):196–202.
Kleindorfer D, et al. Incidence and short-term prognosis of transient ischemic attack in a population-based study. Stroke. 2005;36(4):720–3.
Johnston SC, et al. Short-term prognosis after emergency department diagnosis of TIA. JAMA. 2000;284(22):2901–6.
Wu CM, et al. Early risk of stroke after transient ischemic attack: a systematic review and meta-analysis. Arch Intern Med. 2007;167(22):2417–22.
Giles MF, Rothwell PM. Risk of stroke early after transient ischaemic attack: a systematic review and meta-analysis. Lancet Neurol. 2007;6(12):1063–72.
Clark TG, Murphy MF, Rothwell PM. Long term risks of stroke, myocardial infarction, and vascular death in “low risk” patients with a non-recent transient ischaemic attack. J Neurol Neurosurg Psychiatry. 2003;74(5):577–80.
Ovbiagele B, Kidwell CS, Saver JL. Epidemiological impact in the United States of a tissue-based definition of transient ischemic attack. Stroke. 2003;34(4):919–24.
Redfors P, et al. Stroke subtype predicts outcome in young and middle-aged stroke sufferers. Acta Neurol Scand. 2012;126(5):329–35.
Lee BI, et al. Yonsei Stroke Registry. Analysis of 1,000 patients with acute cerebral infarctions. Cerebrovasc Dis. 2001;12(3):145–51.
Hillen T, et al. Cause of stroke recurrence is multifactorial: patterns, risk factors, and outcomes of stroke recurrence in the South London Stroke Register. Stroke. 2003;34(6):1457–63.
Gorelick PB, Goldstein LB, Ovbiagele B. New guidelines to reduce risk of atherosclerotic cardiovascular disease: implications for stroke prevention in 2014. Stroke. 2014;45(4):945–7.
Dahlof B, et al. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). Lancet. 1991;338(8778):1281–5.
Perry HM Jr, et al. Effect of treating isolated systolic hypertension on the risk of developing various types and subtypes of stroke: the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 2000;284(4):465–71.
Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA. 1991;265(24):3255–64.
Staessen JA, et al. Subgroup and per-protocol analysis of the randomized European Trial on Isolated Systolic Hypertension in the Elderly. Arch Intern Med. 1998;158(15):1681–91.
Bulpitt C, et al. Hypertension in the Very Elderly Trial (HYVET): protocol for the main trial. Drugs Aging. 2001;18(3):151–64.
Nilsson PM. Reducing the risk of stroke in elderly patients with hypertension: a critical review of the efficacy of antihypertensive drugs. Drugs Aging. 2005;22(6):517–24.
Beckett NS, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358(18):1887–98.
Khoury JC, et al. Diabetes mellitus: a risk factor for ischemic stroke in a large biracial population. Stroke. 2013;44(6):1500–4.
Vermeer SE, et al. Impaired glucose tolerance increases stroke risk in nondiabetic patients with transient ischemic attack or minor ischemic stroke. Stroke. 2006;37(6):1413–7.
Kaplan RC, et al. Vascular events, mortality, and preventive therapy following ischemic stroke in the elderly. Neurology. 2005;65(6):835–42.
Eriksson M, Carlberg B, Eliasson M. The disparity in long-term survival after a first stroke in patients with and without diabetes persists: the Northern Sweden MONICA study. Cerebrovasc Dis. 2012;34(2):153–60.
Buse JB, et al. Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association. Circulation. 2007;115(1):114–26.
American Diabetes, A. Standards of medical care in diabetes–2013. Diabetes Care. 2013;36(Suppl 1):S11–66.
Colhoun HM, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004;364(9435):685–96.
Cholesterol Treatment Trialists, C., et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet. 2008;371(9607):117–25.
Ray KK, et al. Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials. Lancet. 2009;373(9677):1765–72.
Control G, et al. Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia. 2009;52(11):2288–98.
Group AC, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560–72.
Kelly TN, et al. Systematic review: glucose control and cardiovascular disease in type 2 diabetes. Ann Intern Med. 2009;151(6):394–403.
Duckworth W, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360(2):129–39.
Kurth T, et al. Lipid levels and the risk of ischemic stroke in women. Neurology. 2007;68(8):556–62.
Blood pressure, cholesterol, and stroke in eastern Asia. Eastern Stroke and Coronary Heart Disease Collaborative Research Group. Lancet. 1998;352(9143):1801–7.
Tirschwell DL, et al. Association of cholesterol with stroke risk varies in stroke subtypes and patient subgroups. Neurology. 2004;63(10):1868–75.
Cholesterol, diastolic blood pressure, and stroke: 13,000 strokes in 450,000 people in 45 prospective cohorts. Prospective studies collaboration. Lancet. 1995;346(8991–8992):1647–53.
Amarenco P, Labreuche J, Touboul PJ. High-density lipoprotein-cholesterol and risk of stroke and carotid atherosclerosis: a systematic review. Atherosclerosis. 2008;196(2):489–96.
Zhang Y, et al. Total and high-density lipoprotein cholesterol and stroke risk. Stroke. 2012;43(7):1768–74.
Varbo A, et al. Nonfasting triglycerides, cholesterol, and ischemic stroke in the general population. Ann Neurol. 2011;69(4):628–34.
Emerging Risk Factors, C., et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009;302(18):1993–2000.
Curb JD, et al. High density lipoprotein cholesterol and the risk of stroke in elderly men: the Honolulu Heart Program. Am J Epidemiol. 2004;160(2):150–7.
Huxley RR, et al. Isolated low levels of high-density lipoprotein cholesterol are associated with an increased risk of coronary heart disease: an individual participant data meta-analysis of 23 studies in the Asia-Pacific region. Circulation. 2011;124(19):2056–64.
Heart Protection Study Collaborative, G. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360(9326):7–22.
Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344(8934):1383–9.
Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med. 1998;339(19):1349–57.
Amarenco P, et al. Statins in stroke prevention and carotid atherosclerosis: systematic review and up-to-date meta-analysis. Stroke. 2004;35(12):2902–9.
Plehn JF, et al. Reduction of stroke incidence after myocardial infarction with pravastatin: the Cholesterol and Recurrent Events (CARE) study. The Care Investigators. Circulation. 1999;99(2):216–23.
Sever PS, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003;361(9364):1149–58.
Amarenco P, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355(6):549–59.
Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA. 2003;289(13):1681–90.
Maddrey WC. Drug-induced hepatotoxicity: 2005. J Clin Gastroenterol. 2005;39(4 Suppl 2):S83–9.
Stone NJ, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 Suppl 2):S1–45.
Ridker PM, Cook NR. Statins: new American guidelines for prevention of cardiovascular disease. Lancet. 2013;382(9907):1762–5.
Wiviott SD, et al. Can low-density lipoprotein be too low? The safety and efficacy of achieving very low low-density lipoprotein with intensive statin therapy: a PROVE IT-TIMI 22 substudy. J Am Coll Cardiol. 2005;46(8):1411–6.
Waters DD, et al. Effects of atorvastatin on stroke in patients with unstable angina or non-Q-wave myocardial infarction: a myocardial ischemia reduction with aggressive cholesterol lowering (MIRACL) substudy. Circulation. 2002;106(13):1690–5.
Mohr JP, et al. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med. 2001;345(20):1444–51.
Chimowitz MI, et al. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med. 2005;352(13):1305–16.
Committee CS. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996;348(9038):1329–39.
Diener HC, et al. European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996;143(1–2):1–13.
Group ES, et al. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet. 2006;367(9523):1665–73.
Diener HC, 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. 2004;364(9431):331–7.
Bhatt DL, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006;354(16):1706–17.
Diener HC, et al. Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial: a double-blind, active and placebo-controlled study. Lancet Neurol. 2008;7(10):875–84.
Gouya G, et al. Antiplatelet treatment for prevention of cerebrovascular events in patients with vascular diseases: a systematic review and meta-analysis. Stroke. 2014;45(2):492–503.
Chimowitz MI, et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med. 2011;365(11):993–1003.
Wang Y, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013;369(1):11–9.
Healey JS, et al. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med. 2012;366(2):120–9.
Tayal AH, et al. Atrial fibrillation detected by mobile cardiac outpatient telemetry in cryptogenic TIA or stroke. Neurology. 2008;71(21):1696–701.
Elijovich L, et al. Intermittent atrial fibrillation may account for a large proportion of otherwise cryptogenic stroke: a study of 30-day cardiac event monitors. J Stroke Cerebrovasc Dis. 2009;18(3):185–9.
Flint AC, et al. Detection of paroxysmal atrial fibrillation by 30-day event monitoring in cryptogenic ischemic stroke: the Stroke and Monitoring for PAF in Real Time (SMART) Registry. Stroke. 2012;43(10):2788–90.
Page RL, et al. Asymptomatic arrhythmias in patients with symptomatic paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia. Circulation. 1994;89(1):224–7.
Strickberger SA, et al. Relationship between atrial tachyarrhythmias and symptoms. Heart Rhythm. 2005;2(2):125–31.
Go AS, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001;285(18):2370–5.
Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22(8):983–8.
Wolf PA, et al. Probability of stroke: a risk profile from the Framingham Study. Stroke. 1991;22(3):312–8.
Wang TJ, et al. A risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community: the Framingham Heart Study. JAMA. 2003;290(8):1049–56.
Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146(12):857–67.
Gage BF, et al. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA. 2001;285(22):2864–70.
Lip GY, et al. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on Atrial Fibrillation. Chest. 2010;137(2):263–72.
Waldo AL, et al. Hospitalized patients with atrial fibrillation and a high risk of stroke are not being provided with adequate anticoagulation. J Am Coll Cardiol. 2005;46(9):1729–36.
Man-Son-Hing M, et al. Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls. Arch Intern Med. 1999;159(7):677–85.
Gage BF, et al. Incidence of intracranial hemorrhage in patients with atrial fibrillation who are prone to fall. Am J Med. 2005;118(6):612–7.
Donze J, et al. Risk of falls and major bleeds in patients on oral anticoagulation therapy. Am J Med. 2012;125(8):773–8.
Connolly SJ, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139–51.
Patel MR, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–91.
Granger CB, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–92.
Banerjee A, et al. Net clinical benefit of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus no treatment in a ‘real world’ atrial fibrillation population: a modelling analysis based on a nationwide cohort study. Thromb Haemost. 2012;107(3):584–9.
Culebras A, et al. Summary of evidence-based guideline update: prevention of stroke in nonvalvular atrial fibrillation: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2014;82(8):716–24.
Eerenberg ES, et al. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation. 2011;124(14):1573–9.
van Ryn J, et al. Dabigatran etexilate—a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost. 2010;103(6):1116–27.
Perzborn E, et al. Reversal of rivaroxaban anticoagulation by haemostatic agents in rats and primates. Thromb Haemost. 2013;110(1):162–72.
Godier A, et al. Evaluation of prothrombin complex concentrate and recombinant activated factor VII to reverse rivaroxaban in a rabbit model. Anesthesiology. 2012;116(1):94–102.
Acknowledgments
This manuscript was written and edited by the authors, who take full responsibility for its content. Martinson K. Arnan receives research support from a Diversity Supplement to contract N01-HC-95165 from the National Heart, Lung, and Blood Institute.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Arnan, M.K., Burke, G.L. & Bushnell, C. Secondary Prevention of Stroke in the Elderly: Focus on Drug Therapy. Drugs Aging 31, 721–730 (2014). https://doi.org/10.1007/s40266-014-0212-2
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40266-014-0212-2