HOPE for Stroke

The Heart Outcomes Prevention Evaluation Study (HOPE) was a landmark trial demonstrating beneficial effects of the angiotensin converting enzyme ramipril on cardiovascular events and disease progression. Several lines of evidence suggest that ACE inhibitors may also lower the risk of ischemic vascular events. ACEIs reduce proliferation of vascular smooth muscle, enhance endogenous fibrinolysis, stabilize plaques and decrease angiotensin II mediated atherosclerosis, plaque rupture and vascular occlusion. These effects suggest that they may reduce transient ischemic events through mechanisms that are independent of reduction in blood pressure. The results of the HOPE trial support this hypothesis.

The primary outcome of HOPE was the composite end point of myocardial infarction, stroke or cardiovascular death, and individual components were analyzed separately. Reduction in blood pressure was modest; however, the relative risk of any stroke was reduced by 32% in the ramipril group compared with the placebo group, and the relative risk of fatal stroke was reduced by 61%.

Benefit was seen at all values of diastolic and systolic blood pressure, confirming that the beneficial effects of ramipril were not confined to those with 'high' blood pressure. The reduction in strokes was consistent across the various subgroups examined, including patients receiving antiplatelet treatment and lipid-lowering drugs. The benefits were also consistent across subgroups defined by the presence or absence of previous stroke, coronary artery disease, peripheral arterial disease, diabetes or hypertension.

These results support those of the PROGRESS trial (perindopril protection against recurrent stroke study), which found that perindopril in combination with indapamide reduced the risk of recurrent strokes by 28% in patients with previous cerebrovascular disease.2,3 The initial blood pressure in this study was higher than in HOPE, and, therefore, was lowered more substantially. Taken together, results from both studies suggest that ACE inhibitors are of benefit in both primary and secondary prevention, even in patients without hypertension. The authors conclude that patients who are at high risk of stroke should be treated with ramipril, irrespective of their initial blood pressure levels and in addition to other preventive treatments such as blood pressure lowering agents and aspirin.

Critics of the study point out that the absolute risk reduction and number needed to treat are not available and do not necessarily support the authors' conclusions.

Source

1. Bosch J, Yusuf S, Pogue J, et al. Use of ramipril in preventing stroke: double blind randomised trial. BMJ 2002; 324:1-5.
2. Neal B, MacMahon S. PROGRESS (perindopril protection against recurrent stroke study): rationale and design. J Hypertens 1995; 13: 1869-73.
3. PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358:1033-41.

A Review of Antiplatelet Therapy in the Secondary Prevention of Stroke in the Elderly

D'Arcy Little, MD, CCFP
Director of Medical Education,
York Community Services, Toronto

Fan-Hsia Mang, BSc
Elective Medical Student,
University of Alberta, Edmonton

Introduction and Background
Stroke is the third leading cause of death in the industrialized world and is a major cause of long-term disability.¹ It is estimated that 40% of patients who survive a first transient ischemic attack (TIA) or stroke will have a subsequent stroke within the next five years.¹ As increased age is one of the major non-modifiable risk factors for stroke, secondary prevention of stroke in the elderly population is an important clinical consideration. The following article will review the antiplatelet medications available for the secondary prevention of stroke in the elderly.

According to current guidelines, patients with a first cerebrovascular event due to cardioembolism should be treated with oral anticoagulants, provided there are no contraindications. This topic has already been reviewed previously in this publication.^2,3,4 Patients who experience cerebrovascular events secondary to atherothrombosis typically receive antiplatelet agents. Aspirin is the best studied antiplatelet agent used for the secondary prevention of stoke, but in the past decade, other agents have been added to the anti-stroke armamentarium, including ticlopidine (Ticlid), clopidogrel (Plavix) and a combination agent containing dipyridamole and ASA (Aggrenox). ⁵

Acetylsalicylic Acid (ASA)
Acetylsalicylic acid (ASA, Aspirin) has been used in clinical practice for decades. It acts by irreversibly inhibiting platelet cyclo-oxygenase, subsequently inhibiting the formation of thromboxane A2. Thromboxane A2 is a vasoconstrictor as well as an activator for platelet aggregation and release.⁶ [See Figure 1: Normal Platelet Function and Antiplatelet Agents]

Early trials, in the 1970's and early 1980's, probing the use of ASA as an antiplatelet agent in the prevention of stroke yielded negative, equivocal or contradictory results, largely due to small sample sizes and population heterogeneity.⁷ In addition, early trials of alternative antiplatelet agents such as sulfinpyrazone and dipyridamole suggested no significant additional benefit over aspirin.^8,9,10

In 1991, however, the United Kingdom Transient Ischemic Attack Trial (UK-TIA) and the Swedish Aspirin Low-dose Trial (SALT) suggested that ASA alone had efficacy for preventing secondary stroke in patients with cerebrovascular disease.^7,11,12 The arm of the Second European Stroke Prevention Study (ESPS-2) in which patients received ASA alone demonstrated, among other things, that ASA alone has a highly significant protective effect. The relative stroke risk was decreased by 18.1% with ASA compared to placebo.^13,14 In addition, a meta-analysis, The Antiplatelet Trialist's Collaboration (APTC), of 25 randomized trials of various forms of antiplatelet therapy used in the treatment of stoke, TIA, unstable angina and myocardial infarction, revealed that antiplatelet therapy was associated with a 27% reduction in nonfatal stroke (p<0.001) and a 25% reduction in stroke, myocardial infarction, or vascular death (p=0.0001). Most of these trials involved ASA.^6,15

Although in the past there has been considerable debate regarding the optimal dose of ASA for secondary stroke prevention, a series of trials have indicated that there is no significant difference in the protective effect of ASA in doses ranging from 30 to 1200 mg/day. Low dose aspirin (50 to 100 mg) reduces the risk of vascular events in patients with prior stroke or TIA by 13%, with no evidence of a dose-response relationship.^7,11,12,16 Furthermore, lower-dose ASA has been associated with a reduced incidence of gastric discomfort and gastric bleeding.^7,17

Aggrenox (Aspirin and Dipyridamole)
Dipyridamole is a platelet inhibitor that is thought to work by inhibiting platelet phosphodiesterase, raising the anti-aggregating effects of cyclic adenosine monophosphate and cyclic guanosine monophosphate.^6,13 In addition, dipyridamole may stimulate prostacyclin synthesis and potentiate the antiplatelet effect of prostacyclin (See Figure 1).⁶ Initial studies in the 1960's seemed to illustrate a lack of efficacy in stroke prevention compared to ASA. In addition, patients taking dipyridamole seemed to experience more adverse side effects such as headache.⁶ In contrast, the ESPS-2 found that both extended-release dipyridamole (200 mg twice daily) and ASA (25 mg twice daily) had an independent and statistically significant effect in reducing the risk of stroke recurrence (16% and 18% respectively), when compared to placebo (p<0.03). In addition, the combination of extended-release dipyridamole plus ASA (Aggrenox), in the above stated doses, had significant and additive effects on preventing stroke recurrence (37% relative risk reduction with p < 0.001), in comparison with placebo. The combination reduced the risk of stroke, both fatal and nonfatal, by 23% compared to aspirin alone.^3,6,13

Common adverse side effects of Aggrenox include headache, dizziness, and gastrointestinal complaints such as dyspepsia, diarrhea and nausea. While the bleeding risk associated with Aggrenox is similar to that of ASA alone, the dose-limiting adverse effects of this agent are comparable to that of dipyridamole alone.⁶ Contraindications to Aggrenox include hypersensitivity to either ASA or dipyridamole, and a history of peptic ulcer disease.

Ticlopidine (Ticlid)
Ticlopidine, a thienopyridine agent, acts by suppressing platelet aggregation induced by adenosine diphosphate (ADP) (See Figure 1).^1,13 Two large, randomized controlled trials have demonstrated that ticlopidine has a protective effect in patients with recent thromboembolic stroke.^18,19 The CATS study, which compared ticlopidine (250mg twice daily) with placebo, concluded that ticlopidine reduces the relative risk of stroke, MI, or vascular death by 30 %.^1,6,18 The TASS study compared ticlopidine (250 mg twice daily) with ASA (650 mg twice daily) and concluded that ticlopidine was associated with a 21% greater relative risk reduction for stroke compared with ASA (p=0.02).^1,6,18

While ticlopidine boasts a fairly mild benefit over ASA in stroke prevention, it is associated with a considerable risk of serious adverse events. There is a 1% incidence of severe, reversible neutropenia, as well as a risk of skin rash, diarrhea, thrombocytopenia, and thrombotic thrombocytopenic purpura (TTP).^1,6,18 Given the rather modest absolute risk reduction with ticlopidine compared to ASA (2% over three years), as well as the need for regular blood monitoring to detect neutropenia, the drug was initially reserved for patients who were intolerant of ASA, or who had recurrent strokes on ASA ("ASA failure"). These potential side effects, coupled with the development of clopidogrel, have limited the use of this medication.^1,19,20

Clopidogrel (Plavix)
Clopidogrel is a new thienopyridine derivative in the same family as ticlopidine (See Figure 1). The CAPRIE (Clopidogrel vs Aspirin in patients at risk of ischemic events) trial, a large, secondary prevention study of patients with recent myocardial infarction, stroke, or peripheral vascular disease, compared the efficacy of clopidogrel (75 mg once daily) to ASA (325 mg once daily). The study showed a significant, 8.7% relative risk reduction for clopidogrel over aspirin (p<0.05) for the combined endpoints of ischemic stroke, myocardial infarction and vascular death.^1,13,21 If one uses the 25% relative risk reduction of ASA found by the Antiplatelet Trialist's Collaboration, it can be extrapolated that clopidogrel imparts a 33% relative risk reduction. The stroke group sub-analysis showed a relative risk reduction of 7.3%, but the p-value was not significant (p=0.26). However, as the CAPRIE study was not designed to detect differences within patient subgroups, such analysis may be inaccurate.^7,21

Clopidogrel has no significant difference in adverse side effects compared to ASA. Unlike ticlopidine, clopidogrel is not associated with neutropenia. While several cases of TTP have been reported with clopidogrel, the incidence is much smaller than that associated with ticlopidine. As a result, routine blood monitoring is not recommended for patients taking clopidogrel.¹³ There has been no head to head comparison of the efficacy of clopidogrel versus ticlopidine, or of clopidogel versus Aggrenox. Due to a modest superiority over ASA but a considerably higher cost, clopidogrel has not replaced ASA as first line therapy in stroke prevention.¹³

Future Research
Due to favourable results in studies of Aggrenox, other combination therapies may play a greater role in the future. For example, the combination of ticlopidine and aspirin has proved superior to conventional anticoagulation plus aspirin in the prevention of cardiac stent thrombosis.²² In addition, clopidogrel and ASA have been shown to act synergistically in the same context.²³ The CURE trial has also recently demonstrated that clopidogrel in combination with ASA reduces the relative risk of the combined endpoints of cardiovascular death, myocardial infarction, and stroke by 20% (p=0.0005) in the context of acute coronary syndromes.^24,25 Studies addressing combinations with specific relevance to stroke prevention are pending.

The platelet glycoprotein (Gp IIb/IIIa) complex is the final common pathway for platelet aggregation. Oral platelet Gp IIb/IIIa antagonists prevent the binding of fibrinogens to platelets, regardless of the trigger for platelet aggregation; therefore, these agents may have a future role in stroke prevention (See Figure 1).

Conclusion/Recommendations
In summary, the above review is synthesized in a list of current recommendations for the secondary prevention of atherothombotic stroke in the elderly:

1. Provided there are no contraindications, every patient who has experienced an atherothrombotic stroke or TIA should receive an antiplatelet agent on a regular basis to reduce the risk of recurrent stroke and other vascular events.³
2. The choice of antiplatelet agent must weigh the risks of stroke against the benefits, risks and costs of treatment.³
3. ASA is recommended as the initial agent. The starting dose should be in the range of 50 to 325 mg. Fewer side effects are experienced at lower doses.^3,13
4. Some clinicians advocate for the use of aspirin plus dipyridamole as first line therapy, although this has not been universally accepted.^1,3,13
5. For patients intolerant to ASA, clopidogrel is recommended over ticlopidine because of a more favourable side effect profile.^3,6
6. For ASA failure, either clopidogrel or dipyridamole and ASA may be selected. Perhaps other combination agents may be used for this indication in the future.¹³

References

1. Sacco RL, Elkind MS. Update on antiplatelet therapy for stroke prevention. Arch Intern Med 2000;160:1579-82.
2. Little DL. Secondary prevention of stoke: the role of antiplatelet and anticoagulant agents. Geriatrics and Aging 2000;3(1):8-9.
3. Albers GW, Easton JD, Sacco RL, Teal P. Antithrombotic and thrombolytic therapy for ischemic stroke. Chest 1998;114(5):683S-698S.
4. Laupacis A, Albers G, Dalen J, Dunn MI, Jacobson AK, Singer DE. Antithrombotic therapy in atrial fibrillation. Chest 1998;114(5):579S-589S.
5. Albers GW, Tijssen JGP. Antiplatelet therapy: new foundations for optimal treatment decisions. Neurology 1999;53(Suppl 4):S25-S31.
6. Lenz TL, Hilleman DE. Aggrenox: a fixed combination of aspirin and dipyridamole. Ann of Pharmacotherapy 2000;34:1283-90.
7. Forbes CD. Antiplatelet therapy for secondary stroke prevention. Scot Med J 1999;44:57-62.
8. Canadian Cooperative Study Group. A randomised trial of aspirin and sulfinpyrazone in threatened stroke. N Engl J Med 1978;299:53-9.
9. Bousser MG, Eschwege E, Haguenau M, Lefaucconnier JM, Thibult N, Touboul C, Touboul PJ. "AICLA" controlled trial of aspirin and dipyridamole in the secondary prevention of atherothrombotic cerebral ischemia. Stroke 1983;14:5-14.
10. American Canadian Cooperative Study Group. Persantine aspirin trial in cerebral ischemia II. Endpoint results. Stroke 1985;16:406-15.
11. SALT Collaborative Group. Swedish aspirin low-dose trial (SALT) of 75 mg aspirin as secondary prophylaxis after cerebrovascular ischemic events. Lancet 1991;338:1345-49.
12. UK-TIA Study Group. United Kingdom transient ischemic attack (UK-TIA) aspirin trial: final results. J Neurol Neurosurg Psych 1991;54:1044-54.
13. Davis SM, Donnan GA. Newer antiplatelet therapies in stroke prevention. Aust. Fam. Phys. 2001;30(2):129-34.
14. Diener HC, Cunha L, Forbes C, Sivenius J, Smets P, Lowenthal A. European Stroke Prevention Study 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J. Neurol. Sci 1996;143:1-13.
15. Antiplatelet Trialist Collaboration. Collaborative overview of randomized trials of antiplatelet therapy. 1. Prevention of death, myocardial infarction and stoke by prolonged antiplatelet therapy in various categories of patients. Br Med J 1994;308:81-106.
16. Tijssen JGP. Low-dose and high-dose acetylsalicylic acid, with and without dipyridamole: A review of clinical trial results. Neurology 1998;51(Suppl3):S15-6.
17. Dutch TIA Trial Study Group. A comparison of two doses of aspirin (30 mg vs. 283 mg a day) in patients after a transient ischemic attack or minor ischemic stroke. N Engl J Med 1991;325:1261-6.
18. Gent M, Blakely JA, Eason JD, et al. The Canadian American ticlopidine study (CATS) in thromboembolic stroke. Lancet 1989;1:1215-20.
19. Hass Wk, Easton JD, Adams HP Jr, Pryse-Phillips W, Molony BA, Anderson S, Kamm B. A randomised trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high risk patients. N Engl J Med 1989;321:501-7.
20. Bennett CL, Weinberg PD, Brosenberg-Ben-Dror K, Yarnold PR, Kwaan HC, Green D. Thrombotic thrombocytopenic purpura associated with ticlopidine: a review of 60 cases. Ann Intern Med 1998;128:541-4.
21. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischemic events (CAPRIE). Lancet 1996;348:1329-39.
22. Schomig A, Neumann FJ, Kastrati A, et al. A randomised comparison of antiplatelet and anticoagulant therapy after the placement of coronary artery stents. N Engl J Med 1996;334:1084-9.
23. Moussa I, Oergen M, Roubin G, et al. Effectiveness of clopidogrel and aspirin versus ticlopidine and aspirin in preventing stent thrombosis after coronary stent implantation. Circ 1999;99:2364-6.
24. Mehta SR, Yusuf S. The Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) Study Investigators. European Heart Journal 2000;(24):2033-41.
25. Beck DL. Clinical Research: CURE Trial finds ASA enhanced by clopidogrel. The Chronicle of Cardiovascular and Internal Medicine 2001 April:1-8.
26.  

A recent study suggests that patients with non-ST-elevation acute coronary syndrome (ACS) may want to hold off on invasive cardiac surgery soon after hospitalization.

A total of 18,151 patients with non-ST-elevation ACS were enrolled in the Organization to Assess Strategies for Ischemic syndromes (OASIS) and the OASIS-2 trials. Data from the two studies were pooled and analyzed to determine the prognostic factors for stroke in this group of patients. Overall, over a 6-month follow-up period, 238 patients had a stroke and multivariate regression analysis identified coronary artery bypass graft (CABG) as the most important predictor of stroke. Furthermore, patients who underwent early CABG surgery were at a substantially increased risk when compared with those who had later CABG. Other prognostic factors identified included history of stroke, diabetes mellitus older age, higher heart rate and on-site catheterization facility. No increased stroke risk was identified for patients who underwent percutaneous coronary intervention.

Source

1. Cronin LC, Mehta SR, Zhao F, et al. Stroke in relation to cardiac procedures in patients with non-ST-elevation acute coronary syndrome. Circulation. 2001;104;269-274.

A Review of Efficacy, Toxicity and Safety Considerations

Charles L Bennett, MD, PhD
The Chicago VA Healthcare
System/Lakeside Division, the Robert H Lurie Comprehensive Cancer Center and
the Division of Hematology/Oncology of the Department of Medicine,
Northwestern University,
Chicago, IL, USA.

Richard H Bennett, MD
Department of Neurology,
Albert Einstein Northern Hospital and
the Medical School of the University of Pennsylvania,
Philadelphia, PA, USA.

Introduction
Stroke is a common cause of morbidity and mortality in older adults in the United States and Canada. Fortunately, in both countries, the age-adjusted national death rate for stroke has declined, reflecting increasingly widespread use of primary and secondary prophylaxis efforts. The mainstay of stroke prevention is the use of antiplatelet agents which interfere with thrombus formation by platelets in diseased or damaged blood vessels (see Figure 1). While aspirin has been the primary antiplatelet agent, over the past ten years, ticlopidine (Ticlid), clopidogrel (Plavix) and extended release dipyridamole plus aspirin (Aggrenox) have been approved for use in this setting.

Scott B. Patten, MD, PhD
Associate Professor,
Departments of Community Health Sciences and Psychiatry,
University of Calgary, Population Health Investigator,
The Alberta Heritage Foundation for Medical Research,
Calgary, AB.

Stroke has the potential to disrupt several facets of a person's life including communication, emotional regulation, cognitive function and coping skills.¹ Furthermore, stroke does not just impact on the individual but also on his or her family members and other social networks of which he or she is a part. Stroke has been regarded as form of "double-jeopardy"¹ in the sense that the condition creates many new problems and challenges for those afflicted, and simultaneously detracts from the afflicted persons' capacity to cope with those challenges. It can also lead to disruptions in those same social connections that would normally support adaptation to loss.

Understanding the role of psychosocial factors in recovery from stroke requires adopting a conceptual viewpoint that transcends the traditional biomedical perspective. A suitable framework is provided by the World Health Organization's International Classification of Impairments, Disabilities and Handicaps (WHO-ICIDH). The WHO system differentiates among impairment, disability and handicap. According to the WHO, impairment is defined as any loss or abnormality of structure or function.

Lin Perry, MSc, RGN, RNT,
Faculty of Health & Social Care Sciences,
Kingston University and St. George's Hospital Medical School:
Sir Frank Lampl Building, Kingston University,
Kingston upon Thames, Surrey, UK.

Introduction
Stroke is a major cause of mortality and morbidity in all industrialized countries¹--incidence of a first-in-a-lifetime stroke in the UK is estimated at 2.4 per 1,000 population per year, with all strokes combined having an incidence 20-30% higher.²

Dysphagia is a frequent accompaniment to stroke.^3-5 Depending upon manner and timing of assessment, dysphagia is detected in 30-65% of acute stroke patients^6-10 with a small proportion experiencing clinically 'silent' aspiration of food/ fluids.^9,10 Dysphagia is associated with increased morbidity and mortality. Whilst this may partly be explained by its relationship with increased stroke severity, dysphagia also exerts an independent effect revealed by the tripling of mortality rates in alert dysphagic stroke patients compared to similar groups with intact swallow.⁸ It is associated with chest infection independent of aspiration⁷ which also risks chemical pneumonitis, infection and airway obstruction.^11,12 Although dysphagia frequently resolves rapidly, for a minority it produces enduring disability and handicap. Stroke-related impaired swallowing has been found in 5.

Dr. Ruth Hubbard
Lecturer

Dr. M. Sinead O'Mahony
Senior Lecturer,
University Department of Geriatric Medicine,
University of Wales,
College of Medicine, Wales, UK.

Introduction
Stroke is the second most common cause of mortality in much of the developed world and leads to an estimated 4.4 milllion deaths per year, worldwide.¹ It also causes significant morbidity. Thirty percent of patients with a stroke will die within the first three months and half of the remaining patients will have significant long-term disability.

Stroke is particularly a problem of older people. The risk of stroke doubles with each decade of life after 35 years, such that two thirds of all strokes occur in patients over the age of 65 years. People over 75 years are the fastest growing population in North America. Any treatment that improves outcomes in elderly patients with stroke is potentially of huge importance.

Until recently, there was no effective therapy or management strategy to reduce stroke mortality and disability. Two interventions have been shown to result in some benefit--stroke units and aspirin therapy. Stroke Unit care is associated with 70 fewer deaths or dependencies per 1000 patients treated.

A familiar drug may have previously unrealized benefits for stroke patients. Results from a landmark six year study of more than 6,000 patients were presented at the European Society of Hypertension (ESH) Congress meeting in Milan earlier this year. The study, 'PROGRESS' (Perinodopril prOtection aGainst REcurrent Stroke Study), was designed to provide evidence regarding the balance of benefits and risks conferred by blood pressure lowering with a perindopril (Coversyl) based regimen among patients with a history of stroke or transient ischemic attack (TIA).

Fifty-eight percent of patients in the study were given perindopril (4 mg) and the diuretic indapamide (Lozide) (2.5 mg) or a placebo daily, and the remaining patients were given perindopril (4 mg) alone or a placebo daily. Participants in the study were free to take any other medications prescribed by their physicians, including other hypertension medications.

Results showed that the ACE inhibitor, perindopril, reduces the incidence of recurrent stroke by 28% compared to placebo; this decrease in stroke rates was seen in both hypertensive and normotensive patients. After an average follow-up of four years, the treatment groups had 50% fewer hemorrhagic strokes overall and 24% fewer ischemic strokes than did the placebo group. In addition, rates of non-fatal MI and dementia due to stroke were both reduced by 38% and 34% respectively in the treatment groups when compared to placebo. Severe cognitive decline due to stroke was reduced by 45%.

World health statistics indicate that about five million people die from stroke every year and at least 15 million others suffer non-fatal strokes that are frequently disabling. About one in five survivors will suffer another stroke or heart attack within five years.

Jocalyn P Clark, MSc, PhD candidate
Department of Health Sciences,
University of Toronto and
The Centre for Research in Women's Health,
Toronto, ON.

Stroke is the third leading cause of death for North American women and the leading cause of long-term disability in Canada. According to the Ontario Ministry of Health and Long-Term Care, in 1994/95 stroke-related costs in the province totaled $857 million. The Canadian Stroke Network estimates annual costs for stroke in Canada to be 2.7 billion dollars. Over the next five years the incidence of stroke is expected to increase by over 30%, and those figures could jump to 68% within two decades. Every year among women, stroke claims more than twice as many lives as does breast cancer. Indeed, according to Dr. Beth Abramson, a cardiologist at St. Michael's Hospital in Toronto and an expert in women and stroke, "The issue of stroke in women is a significant one. This is due to potential bias in treatment of female stroke patients, but also to the greater co-morbidity and health care costs associated with treating women when they suffer from stroke."

Like other cardiovascular conditions, stroke in women is highly age-dependent: women are, on average, several years older than men when they suffer their first stroke and tend to be sicker. Owing to this age dependence, the health burden of stroke will only magnify as the proportion of elderly women in the population increases over time.

There is no doubt that the best outcomes from stroke are achieved with the utilization of a coordinated interdisciplinary approach. This starts from the moment a stroke victim is identified. There is some evidence that a coordinated approach to pre-admission care--i.e. public education, centralized intake to facilitate thrombolysis, availability of neuroradiology, etc.--has a favourable effect on subsequent stroke morbidity. There can also be no doubt that the proper experienced care of a stroke team in the acute hospital is vital to the final outcome. First, the team ensures that an accurate diagnosis is made, and that proper supportive care (nutrition, including swallowing assessment if necessary, early mobilization, attention to skin and continence issues, etc.) and secondary prevention measures (anticoagulation, aspirin, etc.) are commenced.

Some patients can be discharged from hospital directly to their homes, and rely on either outpatient or home rehabilitation programs (if appropriate outpatient diagnostic and follow-up services are available, acute hospital admission is sometimes not necessary in the first place). These are generally patients with minor or no residual deficits. I include education as part of the rehabilitation model, so no patient would be discharged without some form of rehabilitation, even if no traditional speech, physical or occupational therapy is required. Other patients have such severe strokes that, almost immediately, the prognosis is known to be dismal. These patients are usually referred directly to long-term care programs.

However, there is a large number of intermediary patients who benefit from a formal inpatient rehabilitation program. Almost all of these patients are older, which begs the question, 'Should they be admitted to a geriatric rehab program or a stroke program?' Despite being the director of a large and excellent geriatric rehab program, I feel that the bulk of stroke patients should be handled in dedicated stroke units. The reasons for this are straightforward. Geriatric units are, by definition, generalist units. We have to care for patients with multiple problems and multiple medical diagnoses. This is our strength, but also our weakness. Like most skills, stroke rehabilitation is made better by larger volumes and more focus. Geriatric units do well on the motor problems associated with stroke, as these are not that different from those of patients with falls, fractures and deconditioning, who are our bread and butter. However, complex perceptual deficits require a degree of expertise that often overwhelms non-specialized units. However, for selected cases, there is a place for geriatric units in stroke rehabilitation. These are elderly patients who already had functional problems, and then have a stroke, which serves as 'the straw that breaks the camel's back.' These cases usually require attention to multiple problems, not just the stroke, and are better suited to the generalist nature of geriatric rehab. If stroke rehab and geriatric rehab programs are physically close, back and forth consultations are facilitated (even well selected stroke rehab patients can develop geriatric-type syndromes).

In my institution, there is reasonable consensus on most patients. However, one group falls through the cracks. This is previously healthy patients who have had a severe stroke, but who do have the potential to benefit from rehab. These patients often have stroke syndromes that would challenge the most experienced of stroke rehab professionals, and are often beyond the skill set available in geriatric rehab. Unfortunately, the tyranny of length of stay (LOS) is the enemy of these patients. Too specialized for geriatric rehab, they require too many resources from stroke units. I feel that this represents the failure of proper population-based planning. We need to have enough 'long-stay' stroke rehab beds to accommodate these patients. It does not make sense to prevent the most skilled professionals from caring for the most difficult strokes.

This issue has numerous articles on stroke, contributed by an international line-up of authors. Drs. Kennedy and Buchan discuss acute therapy in ischemic stroke, while Dr. Patten gives us information on some of the psychosocial issues involved. There are also articles on tests (reaction time) that predict recovery from acute stroke (Loranger and Doyon), gender issues in stroke (Clark), and the management of dysphagia in patients post-stroke (Perry). Several authors review the use of medications for primary and secondary stroke prophylaxis, including an article on the treatment of hyperlipidemia (Aronow), thrombolysis in elderly patients (O'Mahony), antithrombotic drugs for secondary stroke prophylaxis (Bennett and Bennett) and new frontiers in the treatment of stroke (Gladstone et al).

As well, we have our usual potpourri of geriatric articles. The topic of our ethics column this month is the ethics of receiving our flu vaccination (Sheehan and Gordon). The mental health column focuses on an atypical psychotic disorder, Capgras Syndrome (Sloan). In the Biology of Aging column, Dr. Mattson provides information on neuroplasticity and how the brain adapts to aging. The cancer column examines quality surgical cancer care in Ontario (Gagliardi)--a topic that has recently been much in the news--and for our Dementia column, Drs. Tong and Corey-Bloom from the University of California San Diego, review galantamine, a new medication for the treatment of Alzheimer disease.

Enjoy this issue.