(Stroke. 2005;36:526.)
© 2005 American Heart Association, Inc.
Letters to the Editor |
Use of Magnetic Resonance Imaging in Predicting Further Vascular Events Among Patients With Transient Ischemic Attacks
University of Calgary, Calgary, Alberta, Canada
To the Editor:
In the October 2004 issue of Stroke, Purroy et al reported a higher risk of further vascular events among transient ischemic attack (TIA) patients with diffusion-weighted imaging (DWI) acute ischemic lesions.1 They prospectively studied 83 patients with TIA and suggested that duration of symptoms (>60 minutes), presence of DWI acute ischemic lesion, and large vessels disease were important risk factors for the recurrence of vascular events, including cerebrovascular ones.
However, only a minority (9.6%) of patients had their magnetic resonance imaging performed (MRI) within 2 days of symptom onset.1 As quoted by the authors, 10.5% of patients with TIA will have a stroke within the next 90 days of their TIA, and 25% to 50% of these have their stroke within the first 24 to 48 hours.2,3 Therefore, a substantial portion of MRI data may show a second cerebrovascular ischemic event instead of the first stroke/TIA and subsequently do not predict the primary outcome. We would like to know the proportion of clinically defined early/late new vascular events.
Second, the inclusion of TIA as a primary endpoint is problematic and not conventional in relation to stroke prevention trials.4–8 The percentage of patients with TIA versus stroke at outcome should be stated.
Third, a significant proportion of patients presented with vertebrobasilar (43.4%) TIA. What symptoms were accepted as diagnosis of vertebrobasilar TIA? Isolated "dizziness" of unclear origin, for example, is sometimes diagnosed as possible vertebrobasilar TIA but has multiple alternate differential diagnoses that may not ever be conclusively determined. It would have been interesting to know the proportion of vertebrobasilar and carotid TIA among patients with DWI acute ischemic lesions and further vascular events.
Fourth, there are some issues regarding the treatments provided to this cohort that might affect the prognosis of patients. In particular, 54.2% of those enrolled were hypertensive but only 24.1% received antihypertensive medication.1 Furthermore, 15.7% had a severe (>70%) carotid stenosis but only 6% had endarterectomy at discharge. Were these treatments initiated later?
We agree with the conclusion of the authors that MRI may be particularly useful in predicting the future risk of stroke in patients with TIA. MRI should be evaluated with other neuroimaging techniques (transcranial Doppler, etc) to best-predict those minor strokes and TIAs at risk of new events that would lead to the identification of a new target population for acute stroke prevention trials.
References
- Purroy F, Montaner J, Rovira A, Delgado P, Quintana M, Alvarez-Sabin A. Higher risk of further vascular events among transient ischemic attacks patients with diffusion-weighted imaging acute ischemic lesions. Stroke. 2004; 35: 2313–2319.
[Abstract/Free Full Text] - Johnston SC, Gress DR, Browner WS, Sidney. Short-term prognosis after emergency department diagnosis of TIA. JAMA. 2000; 284: 2901–2906.
[Abstract/Free Full Text] - Eliasziw M, Kennedy J, Hill MD, Buchan AM, Barnett HJ. North Am Symptomatic Carotid Endarterectomy Trial Group. Early risk of stroke after a transient ischemic attack in patients with internal carotid artery disease. CMAJ Can Med Assoc J. 2004; 170: 1105–1109.
- CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996; 348: 1329–1339.[CrossRef][Medline] [Order article via Infotrieve]
- CAST (Chinese Acute Stroke Trial) Collaborative Group. CAST: a randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. Lancet. 1997; 349: 1641–1649.[CrossRef][Medline] [Order article via Infotrieve]
- Diener HC, Cunha L, Forbes C, Sivenius J, Smets P, Lowenthal A. European Stroke Prevention Study 2. Dypiridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996; 143: 1–13.[CrossRef][Medline] [Order article via Infotrieve]
- International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19,435 patients with acute ischaemic stroke. Lancet. 1997; 349: 1569–1581.[CrossRef][Medline] [Order article via Infotrieve]
- Hass WK, Easton JD, Adams HP Jr, Pryse-Phillips W, Molony BA. Anderson S. Kamm B. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. Ticlopidine Aspirin Stroke Study Group. N Engl J Med. 1989; 321: 501–507.[Abstract]
Response:
Neurovascular Unit (Department of Neurology), Hospital Universitari de la Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
We thank Boulanger et al for their interest in our article. As they mentioned, we studied 83 patients with transient ischemic attack (TIA), showing that patients with the duration of symptoms lasting for >1 hour in association with the presence of diffusion-weighted imaging (DWI) acute ischemic lesions and large vessel disease were at highest risk for new cerebral ischemic and any vascular event within the follow-up period (mean of 389 days).1
They raise an interesting point, that is the moment in which DWI study was performed. Ideally, MRI should be obtained as close to the index TIA as possible, to avoid new events being responsible of the brain lesion if any. To limit this issue, we performed DWI acutely (mean of 3 days), and we restricted the inclusion time window for getting the MRI to 7 days after symptoms onset, that was the time point from which we considered recurrences and new vascular events. A cluster of TIAs present within 7 days of the index event occurred in 31 cases as stated in Table 2,1 and it was not considered as a recurrence. To avoid that these cases could be a confounding factor, we included the presence of a cluster of TIAs in the logistic regression. It was the presence of DWI lesions but not the presence of multiple TIAs that predicted the risk of recurrence; moreover, those patients had not a higher hazard of having a DWI lesion than patients with a single TIA. In fact, a subset of patients with presumed TIA with a benign short-term course and multiple brief TIAs has been previously described.2 Whether multiples TIAs might induce ischemic tolerance remains to be elucidated.
The commonly quoted risk of stroke within the first 2 days after a TIA varies from 1.4% to 5.5%, depending on the inclusion criteria of different studies.3–6 This means that from a theoretical point of view, in our cohort from 1 to 4 patients might have a stroke within the first 2 days, and a proportion of them might receive the MRI in a delayed fashion. Although this point did not occur in our study, because in every case MRI was done before a new follow-up stroke appeared, it could have happened in a larger sample size cohort and should be taken into account.
Regarding vascular events, as we consider that TIA and cerebral ischemic infarcts share the same underlying pathophysiology, brain ischemia, we include TIA as a primary end point. We understand that studies, such as stroke prevention trials,7–9 that are not entirely conducted by neurologists should take care about TIA inclusion and definitions, but this shouldn’t be a caveat for stroke neurologists.
In fact, the results of our study were similar even when separating cerebral end points into TIA (n=9) and stroke (n=7) as suggested by Boulanger et al. Among those TIA patients with a positive DWI, stroke recurrence rate was 15.4% and TIA recurrence rate 14.8%. In contrast, those TIA patients with a negative DWI had lower stroke (7.1%) and TIA (8.9%) recurrence rates. Because sample size is too small for this type of subanalysis, we decided to pool that information in the original article.
According to neurological symptoms, patients were classified in 3 subtypes of TIA: carotid territory in 47 patients (56.6%), vertebrobasilar territory in 15 patients (18.1%), and uncertain territory in the remaining 21 patients (25.3%). We defined vertebrobasilar TIA strictly. We did not consider isolated dizziness, vertigo, drop attack, dysartria, syncope, or amnesia as symptoms suggestive of vertebrobasilar TIA. The proportion of vertebrobasilar TIA among patients with further vascular events is 40% (6 patients), 27% (13 patients) for carotid TIA, and 4.8% (1 patient) for uncertain territory TIA. The ratio of DWI acute ischemic lesions is also higher in patients with vertebrobasilar TIA, 60% (9 patients), than in patients with carotid TIA, 36.2% (17 patients). Both factors, higher recurrence rate and higher DWI abnormalities among vertebrobasilar TIAs, claim in favor of the correct selection of this TIA subtype.
We agree with Boulanger et al that currently available treatments, such as lipid lowering or antihypertensive therapies, are likely to affect the stroke risk. As they pointed out, 54.2% of the cohort was hypertensive, 78.4% of whom received any antihypertensive medication previously. Moreover, 56.7% of the antihypertensive patients (the 24.1% indicated in the article) were given drugs that modulate the renin-angiotensin-aldosterone system. We focused on the study of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blocker because recently their role has been demonstrated in the prevention of recurrent stroke independently of blood pressure reduction.10–12
Regarding large-artery occlusive disease, 13 patients (15.7%) had severe extracranial stenoses, and endarterectomy was performed before discharge in 5 of those cases. In the remaining cases, this treatment was conducted within the following weeks. Although most neurologists believe that in TIA patients, if a high-grade stenosis is identified, an urgent vascular surgery referral is required, some vascular surgeons prefer to delay endarterectomies in the presence of a recent infarction, because they are afraid of bleeding complications. Paradoxically, we believe that some of our TIA patients had a delayed endarterectomy because of the acute lesions in DWI, in spite of being the highest risk patients. Surgeons have to make an effort to better work with this new information close to neurologists.
In this study, DWI results did not condition neurologist management of the patient. We hypothesize that when most of TIA patients might receive a DWI and Doppler ultrasonographic examination in the hyperacute phase, to identify those at high risk to plan adequate and most aggressive prevention therapies, vascular event recurrence will be reduced.
We agree with Boulanger et al and others13 that there are areas of important practice variability in the management of TIAs. DWI studies to guide patient care decisions in TIA patients seems promising if our data are confirmed in larger TIA populations. We emphasize that there are some patients, particularly patients with DWI abnormalities associated with long duration of symptoms and large-artery disease, who will benefit from early aggressive therapeutic and preventive strategies.
References
- Purroy F, Montaner J, Rovira A, Delgado P, Quintana M, Alvarez-Sabin J. Higher risk of further vascular events among transient ischemic attack patients with diffusion-weighted imaging acute ischemic lesions. Stroke. 2004; 35: 2313–2319.
[Abstract/Free Full Text] - Johnston SC, Sidney S, Bernstein AL, Gress DR. A comparison of risk factors for recurrent TIA and stroke in patients diagnosed with TIA. Neurology. 2003; 60: 280–285.
[Abstract/Free Full Text] - Hill MD, Yiannakoulias N, Jeerakathil T, Tu JV, Svenson LW, Schopflocher DP. The high risk of stroke immediately after transient ischemic attack: a population-based study. Neurology. 2004; 62: 2015–2020.
[Abstract/Free Full Text] - Eliasziw M, Kennedy J, Hill MD, Buchan AM, Barnett HJ. Early risk of stroke after a transient ischemic attack in patients with internal carotid artery disease. CAMJ. 2004; 170: 1105–1109.
- Johnston SC, Gress DR, Browner WS, Sydney S. Short-term prognosis after emergency department diagnosis of TIA. JAMA. 2000; 284: 2901–2906.
[Abstract/Free Full Text] - Lovett JK, Dennis MS, Sandercock PA, Bamford J, Warlow CP, Rothwell PM. Very early risk of stroke after a first transient ischemic attack. Stroke. 2003; 34: e138–e140.[Medline] [Order article via Infotrieve]
- A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE steering committee. Lancet. 1996; 348: 1329–1339.[CrossRef][Medline] [Order article via Infotrieve]
- Diener HC, Cunha L, Forbes C, Sivenius J, Smets P, Lowenthal A. European stroke prevention study. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996; 143: 1–13.[CrossRef][Medline] [Order article via Infotrieve]
- Hass WK, Easton JD, Adams HP, Jr., Pryse-Phillips W, Molony BA, Anderson S, Kamm B. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. Ticlopidine Aspirin Stroke Study Group. N Engl J Med. 1989; 321: 501–507.[Abstract]
- Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000; 342: 145–153.
[Abstract/Free Full Text] - Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, Fyhrquist F, Ibsen H, Kristiansson K, Lederballe-Pedersen O, Lindholm LH, Nieminen MS, Omvik P, Oparil S, Wedel H; LIFE Group. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002; 359: 995–1003.[CrossRef][Medline] [Order article via Infotrieve]
- Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet. 2001; 358: 1033–1041.[CrossRef][Medline] [Order article via Infotrieve]
- Johnston SC, Smith WS. Practice variability in management of transient ischemic attacks. Eur Neurol. 1999; 42: 105–108.[CrossRef][Medline] [Order article via Infotrieve]
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