Perspectives in Cardiology / September 2003 39

Of stroke survivors, 8.8% will have anoth-er stroke within six months of the first.1

Of patients presenting with a transientischemic attack (TIA), 10.5% will progress to acompleted stroke within 90 days.2 These patientswill also be at greater risk of cardiovascular events,and cardiac death.2

It is, therefore, vital that these patients areinvestigated appropriately and rapidly. The evi-dence base for subsequent treatment has advancedgreatly in recent years, along with an understand-ing of the underlying mechanism of endothelialand systemic inflammation, which may help iden-tify those at greatest risk.

What is the role of antiplatelets?The role of acetylsalicylic acid (ASA) in the sec-ondary prevention of ischemic stroke is well-estab-lished. It reduces the risk of early recurrence by30% if commenced within the first 48 hours, with

benefits maintained in the longer-term.3 Low dosesof ASA, such as 81 mg, are as efficacious as high-er doses.4 Part of the protection afforded by ASAmay be mediated by its anti-inflammatory actions.It provides a significant reduction in the risk ofmyocardial infarction (MI) in men among the

Many physicians will encounter stroke on adaily basis in their office practice. They may beconsulted by patients at risk of a first stroke orby survivors of a prior event who wish to avoida recurrence.

By F. O’Rourke, MD, MRCP(UK); N. Dean, MD, MRCP(UK);N. Akhtar, MD; and A. Shuaib, MD, FRCPC

Stroke Preventionin the Office:What’s My Role?

1. What is the role ofantiplatelets?

2. How much effect does anticoagulation have onstroke?

3. What’s the correlationbetween carotid disease andstroke?

4. What is my role as a GP?

In this article:

Perspectives in Cardiology / September 200340

highest quartile of C-reactiveprotein, but not in those in thelowest quartile.5

The addition of dipyri-damole SR to ASA furtherreduces the long-term risk ofstroke. The relative riskreduction (RRR) is 37%,compared to 18% for ASAalone, and this combination isrecommended for recurrentatherothrombotic stroke.6

Clopidogrel has beenshown to be superior to ASAin reducing a combined vas-cular end point of MI, periph-eral vascular disease, andstroke. It is considerably more costly, however, and isindicated as a sole agent only if ASA is contraindicated.7

Studies of its efficacy in combination with ASA forstroke prevention are ongoing. This combination hasalready proven to be of benefit following acute coronarysyndromes, outweighing the small increased hemor-rhage rate.8

Antiplatelets are not recommended as primaryprevention in those without vascular disease. There

is little or no reduction in ischemic stroke but a sig-nificant increase in intra-cranial and gastrointestinalhemorrhage.9

How much effect does anticoagulation have on stroke?Atrial fibrillation (AF) confers an annual stroke risk of5%, rising to 12% in those with a prior TIA/stroke, andmitigated by other high-risk factors.10,11 Anticoagulationreduces this risk by approximately two-thirds, and isrecommended for all AF patients as long-term sec-ondary stroke prevention, pending individual safetyconsiderations. ASA may be sufficient as primary pre-vention in those under 65, or in those with no risk fac-tors (Table 1), for whom the risk of stroke may be as lit-tle as 1% a year.10 Although ASA is considerably lessprotective as secondary prevention with AF, it is pre-ferred to anticoagulation in the first one to two weeksafter a stroke. During this period, the risk of stroke recur-rence is low, and the benefits of anticoagulation are out-weighed by the risk of intracranial hemorrhage.12

There are few other definitive indications for antico-agulation in stroke prevention. These include patients

Stroke Prevention

Age Treatment Risk factors

< 65 1. hypertension• no risk factors acetylsalicylic acid (ASA) 2. left ventricular disease• 1 or more risk factors warfarin (international 3. diabetes mellitus

normalized ratio 2-3) 4. coronary artery disease5. thyrotoxicosis

65-75• no risk factors ASA or warfarin• 1 or more risk factors warfarin

> 75 warfarin

Table 1

Treatment of atrial fibrillation in primary stroke prevention

About the authors

Dr. O’Rourke is a stroke fellow, University of AlbertaHospital, Edmonton, Alberta, and trained as an internistin the U.K.

Dr. Dean is a clinical associate professor, department of medicine, Royal Alexandra Hospital,Edmonton, Alberta.

Dr. Akhtar is a stroke fellow, University of AlbertaHospital, Edmonton, Alberta.

Dr. Shuaib is a professor of neurology, University ofAlberta Hospital, Edmonton, Alberta.

Stroke Prevention

with mechanical heart valves, and stroke withpositive anti-phospholipid antibody.13,14 It mayalso be reasonable to anticoagulate patients forthree to six months fol-lowing strokes caused byextracranial arterial dis-section.15 Whether otherpotential sources ofembolic stroke, such aspatent foramen ovale andaortic atheroma should betreated with anticoagula-tion or antiplatelets, continues to be studied. Forprevention of atherothrombotic stroke, anticoagu-lation offers no advantage over antiplatelet treat-ment, but considerably increasesmorbidity from major hemorrhage.1

How serious ishypertension?The benefits of reducing blood pres-sure (BP) for primary prevention ofstroke are long established. A reduc-tion in diastolic BP of as little as 6mmHg reduces the relative risk ofstroke by 38% over five years.17

Several studies, including the recentAntihypertensive and Lipid-Lowering treatment to prevent HeartAttack Trial (ALLHAT), demon-strate little difference in efficacybetween the many agents used forprimary prevention.18 Given their rel-ative low cost, thiazide diuretics are areasonable first-line therapy unlessother co-morbidities favour an alter-native agent, with a target BP of lessthan 140/90 mmHg. Following a TIAor stroke, a thiazide should be com-bined with an angiotensin convertingenzyme inhibitor (ACEI), reducing

the risk of recurrence by 43% in the PerindoprilpROtection aGainst REcurrent Stroke Study(PROGRESS).19 In these patients, as with those

with diabetes or other vas-cular disease, the targetBP should be lower at130/80 mmHg.20

What aboutdyslipidemia?Treatment of dyslipidemia

with statin drugs reduces the incidence of bothcerebrovascular and coronary events, despite thelack of correlation between stroke and elevated

A reduction indiastolic BP of aslittle as 6 mmHg

reduces the relativerisk of stroke by 38%

over 5 years.

Lipidil SUPRATM is indicated as an adjunct to diet and other therapeutic measures for the treat-ment of: patients with Fredrickson classification type IIa hypercholesterolemia and IIb mixedhyperlipidemia, to reduce serum triglycerides (TG) and LDL cholesterol levels, and elevate HDLcholesterol; adult patients with very high serum TG levels, Fredrickson classification type IV andtype V hyperlipidemias, at high risk of sequelae and complications from their hyperlipidemia. Product Monograph available on request from Fournier Pharma Inc., Montreal, Quebec H3A 2R7.

www.fournierpharma.ca LS 1

8-03

03E

® Product developed and manufactured by Laboratoires Fournier S.A., Dijon, France.

TM Lipidil SUPRATM is a trademark of Fournier Pharma Inc.2003 Fournier Pharma Inc., Montreal Quebec H3A 2R7

Perspectives in Cardiology / September 200342

cholesterol levels, and the lack of efficacy of otherlipid-lowering interventions.21,22 This again points to ananti-inflammatory role at the endothelial level, with thelargest risk reductions occurring in those with the high-est C-reactive protein, independent of low-densitylipoprotein (LDL) lowering.23

This principle was reinforced by the HeartProtection Study, in which patients with prior arterialdisease, hypertension or diabetes and LDL as low as2.5 mmol/L had a 30% RRR in ischemic stroke.24 Thissuggests all patients with prior TIA or stroke should betreated with a statin, regardless of their lipid levels. Asprimary prevention, statin treatment appears to be morebeneficial in the prevention of coronary disease thanstroke. However, the recent Anglo-ScandinavianCardiac Outcomes Trial Lipid Lowering Arm (ASCOT-LLA) trial demonstrated a 27% RRR in stroke forhypertensive patients, with LDL 6.5 mmol/L or less,and three or more other vascular risk factors but nocoronary disease.25

What is the correlationbetween carotid disease and stroke?Symptomatic severe carotid stenosis of 70% or moreconfers an ipsilateral stroke risk of 26% over two years.As carotid endarterectomy reduces this risk to 9%(RRR 65%), carotid ultrasound should be soughturgently when patients with TIA or minor, non-dis-abling strokes are seen in the office.26 Auscultation of

the carotid arteries is unreliable, as a bruit may beabsent in over a third of patients with severe stenosis.27

Patients with moderate carotid stenosis (50% to 69%)may also benefit from surgery, but to a lesser extent.Although advocated by some, we do not currently rec-

Stroke Prevention

Table 2

Benefits of carotid enderterectomy versusbest medical management

Severity of internal Number needed to treatcarotid artery stenosis

Symptomatic 70-90% 8 to save 1 stroke at 2 years

Symptomatic 50-69% 20 to save 1 stroke at 2 years

Asymptomatic > 60% 83 to save 1 stroke at 2 years

• Of stroke survivors, 8.8% will have anotherstroke within the following six months.

• Of patients presenting with a TIA, 10.5% willprogress to a completed stroke within 90 days.

• Acetylsalicylic acid reduces the risk of earlyrecurrence stroke by 30% if commenced withinthe first 48 hours.

• Atrial fibrillation confers an annual stroke risk of5%, rising to 12% in those with a prior TIA/stroke,and mitigated by other high risk factors.

• Symptomatic severe carotid stenosis of 70% ormore confers an ipsilateral stroke risk of 26%over two years.

• Patients with prior stroke should have a targetBP of 130/80 mmHg or less.

• As early as two years after smoking cessation,the risk of stroke may be equivalent to that of anon-smoker.

• Excess consumption of alcohol (> 60 grams aday) increases the risk of ischemic and hemorrhagic stroke.

• All patients with stroke should be considered forstatin therapy, irrespective of their cholesterollevel.

Take-home message

www.stacommunications.com

For an electronic version of this article, visit Perspectives in

Cardiology online.

See page 30 for Frequently Asked Questionson stroke prevention in the office.

Stroke Prevention

ommend surgery to our patients with asympto-matic disease, who benefit even less (Table 2).28 Inthese patients, 45% of the ipsilateral strokes will besecondary to other disease, such as cardio-embolism or small vessel disease.29 Greater atten-tion should perhaps be given to modifyingpatients’ overall vascular risk, as the likelihood ofMI and non-stroke vascular death outweighs theirrisk of stroke.30

Is lifestyle modificationbeneficial in reducing stroke risk?In addition to the medical and surgical interven-tions, a patient should be encouraged to takeresponsibility for modifying their vascular riskthrough lifestyle changes. As early as two yearsafter smoking cessation, the risk of stroke maybe equivalent to that of a non-smoker.31 Excessconsumption of alcohol (> 60 grams a day)increases the risk of both ischemic and hemor-rhagic stroke, and should be discouraged,although moderate alcohol intake (12 g to 24 ga day) may protect against ischemic stroke(RRR 28%).32 Vigorous daily exercise reducesthe risk of ischemic stroke by as much as 48%,and also helps in weight reduction.33 Each unitof body mass index above 23 adds an addition-al 6% risk.34

What is my role asa general practitioner?Appropriate investigation and risk modifica-tion in the office may prevent both initial andrecurrent strokes. Evidence-based treatmenttargets and thresholds should be aggressivelymonitored by both physicians and patients.

References1. Hankey GJ, Jamrozik K, Broadhurst RJ, et al: Long-term risk of

first recurrent stroke in the Perth Community Stroke Study.Stroke 1998; 29(12):2491-500.

2. Johnston SC, Gress DR, Browner WS, et al: Short-term progno-sis after emergency department diagnosis of TIA. JAMA 2000;284(22):2901-6.

3. Chen ZM, Sandercock P, Pan HC, et al: Indications for earlyaspirin use in acute ischemic stroke: A combined analysis of40,000 randomized patients from the Chinese acute stroke trialand the international stroke trial. On behalf of the CAST and ISTcollaborative groups. Stroke 2000; 31(6):1240-9.

4. Johnson ES, Lanes SF, Wentworth CE 3rd, et al: A meta-regression analysis of the dose-response effect of aspirinon stroke. Arch Intern Med 1999; 159(11):1248-53.

5. Ridker PM, Cushman M, Stampfer MJ, et al: Inflammation,aspirin, and the risk of cardiovascular disease in apparentlyhealthy men. N Engl J Med 1997; 336(14):973-9.

6. Franck G: 2nd European study on secondary prevention ofstroke (ESPS 2): Respective roles of acetylsalicylic acid, dipyri-damole and their combination. Rev Med Liege 1995;50(11):491.

7. A randomised, blinded, trial of clopidogrel versus aspirin inpatients at risk of ischaemic events (CAPRIE). CAPRIE SteeringCommittee. Lancet 1996; 348(9038):1329-39.

8. Yusuf S, Zhao F, Mehta SR, et al: Effects of clopidogrel in addi-tion to aspirin in patients with acute coronary syndromes withoutST-segment elevation. N Engl J Med 2001; 16:345(7):494–502.

rosuvastatin calci

Pr

PCard

Perspectives in Cardiology / September 200344

9. Sanmuganathan PS, Ghahramani P, Jackson PR, et al: Aspirinfor primary prevention of coronary heart disease: Safety andabsolute benefit related to coronary risk derived from meta-analysis of randomised trials. Heart 2001; 85(3):265-71.

10. Risk factors for stroke and efficacy of antithrombotic therapy inatrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch Intern Med 1994;154(13):1449-57.

11. Secondary prevention in non-rheumatic atrial fibrillation aftertransient ischaemic attack or minor stroke. EAFT (EuropeanAtrial Fibrillation Trial) Study Group. Lancet 1993;342(8882):1255-62.

12. Hart RG, Palacio S, Pearce LA: Atrial fibrillation, stroke, andacute antithrombotic therapy: Analysisof randomized clinical trials. Stroke2002; (11):2722-7.

13. Stein PD, Alpert JS, Bussey HI, et al:Antithrombotic therapy in patients withmechanical and biological prostheticheart valves. Chest 2001; 9(1 Suppl):220S-227.

14. Khamashta MA, Cuadrado MJ, Mujic F,et al: The management of thrombosis inthe antiphospholipid-antibody syndrome. N Engl J Med 1995;332(15):993-7.

15. Treiman GS, Treiman RL, Foran RF etal: Spontaneous dissection of the internal carotid artery: A nineteen-year clinical experience. J Vasc Surg 1996;(4):597-605.

16. Hankey GJ: Warfarin-Aspirin RecurrentStroke Study (WARSS) trial: Is warfarinreally a reasonable therapeutic alternative to aspirin for preventing recurrent noncardioembolic ischemic stroke? Stroke2002; 33(6):1723-6.

17. Collins R, MacMahon S: Blood pressure, antihypertensive drugtreatment and the risks of stroke and of coronary heart disease.Br Med Bull 1994; 50(2):272-98.

18. Major outcomes in high-risk hypertensive patients randomizedto angiotensin-converting enzyme inhibitor or calcium channelblocker vs diuretic: The Antihypertensive and Lipid-LoweringTreatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002;288(23):2981-97.

19. PROGRESS Collaborative Group. Randomised trial of aperindopril-based blood-pressure-lowering regimen among6,105 individuals with previous stroke or transient ischaemicattack. Lancet 2001; 358(9287):1033-41.

20. McAlister FA, Zarnke KB, Campbell NRC, et al: For CanadianHypertension Recommendations Working Group. The 2001Canadian recommendations for the management of hypertension: Part two—Therapy. Can J Cardiol 2002;18(6):625-41.

21. Neaton JD, Blackburn H, Jacobs D, et al: Serum cholesterollevel and mortality findings for men screened in the Multiple RiskFactor Intervention Trial. Multiple Risk Factor Intervention TrialResearch Group. Arch Intern Med 1992; 152(7):1490-500.

22. Di Mascio R, Marchioli R, Tognoni G: Cholesterol reduction andstroke occurrence: an overview of randomized clinical trials.Cerebrovasc Dis 2000; 10(2):85-92.

23. Ridker PM, Rifai N, Clearfield M, et al: Air Force/Texas CoronaryAtherosclerosis Prevention Study Investigators. Measurement ofC-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med2001; 344(26):1959-65.

24. Heart Protection Study Collaborative Group. MRC/BHF HeartProtection Study of cholesterol lowering with simvastatin in20,536 high-risk individuals: A randomised placebo-controlledtrial. Lancet 2002; 360(9326):7-22.

25. Sever PS, Dahlöf B, Poulter NR, et al: Prevention of coronary and stroke events with atorvastatin in hypertensivepatients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian CardiacOutcomes Trial––Lipid Lowering Arm (ASCOT-LLA): A multicentre randomised controlled trial. Lancet 2003;361(9364):1149-58.

26. Beneficial effect of carotid endarterectomy in symptomaticpatients with high-grade carotid stenosis. North American

Symptomatic Carotid EndarterectomyTrial Collaborators. N Engl J Med 1991;325(7):445-53.27. Sauve JS, Thorpe KE, Sackett DL:

Can bruits distinguish high-gradefrom moderate symptomatic carotidstenosis? The North AmericanSymptomatic CarotidEndarterectomy Trial. Ann InternMed. 1994; 120(8):633-7.

28. Gorelick PB: Carotid endarterectomy:Where do we draw the line? Stroke1999; (9):1745-50.

29. Inzitari D, Eliasziw M, Gates P, et al:The causes and risk of stroke inpatients with asymptomatic internal-carotid-artery stenosis. NorthAmerican Symptomatic CarotidEndarterectomy Trial Collaborators. NEngl J Med 2000; 342(23):1693-700.

30. Nadareishvili ZG, Rothwell PM, Beletsky V, et al: Long-term riskof stroke and other vascular events in patients with asymptomatic carotid artery stenosis. Arch Neurol 2002;59(7):1162-6.

31. Kawachi I, Colditz GA, Stampfer MJ, et al: Smoking cessation and decreased risk of stroke in women. JAMA 1993;269(2):232-6.

32. Reynolds K, Lewis LB, Nolen JD, et al: Alcohol consumptionand risk of stroke: A meta-analysis. JAMA 2003; 289(5):579-88.

33. Hu FB, Stampfer MJ, Colditz GA, et al: Physical activity and riskof stroke in women. JAMA 2000; 283(22):2961-7.

34. Kurth T, Gaziano JM, Berger K, et al: Body mass index and therisk of stroke in men. Arch Intern Med 2002; 162(22):2557-62.

Stroke Prevention

Net Readings1. The Internet Stroke Center:

www.strokecenter.org

2. American Stroke Association:www.strokeassociation.org

3. Health Canada:www.hc-sc.gc.ca

For a good move see page 14

For a good move see page 14