TO THE EDITOR: Dr Solenski's review...

TO THE EDITOR: Dr Solenski's review (1) of treatment options for transient ischemic attack (TIA) discusses the additive benefits of combination therapy with aspirin and extended-release dipyridamole (Persantine), compared with placebo or aspirin alone, as noted in the European knock Prevention Study 2 (ESPS-2). (2) however, Dr Solenski raises a be of importance to that the "expected similar benefits for reducing myocardial infarction and vascular death were not observed" (1) this be of importance to is misplaced because a trial limited to knock patients would not be calculate uponed to show such benefits.

ESPS-2 no other than enrolled patients with recent ischemic affliction or TIA (2). Such patients are overwhelmingly more likely to have a renewed stroke than a myocardial infarction during the two-year follow-up period of the trial. (3) Although a nonsignificant direction toward reduction of myocardial infarction in favor of aspirin and combination therapy was seen in ESPS-2 (2) there were simply too not many myocardial infarction endpoints to draw any firm conclusion. this paucity of myocardial infarction endpoints in hit patients has occurred in other antiplatelet trials. In the Clopidogrel versus Aspirin in Patients at risk of ischemic occurrences (CAPRIE) trial, (4) patients enlisted after a stroke were seven times more likely to have a hardship than a myocardial infarction during the follow-up period. More strikingly, the late Management of Atherothrombosis with Clopidogrel in high-risk Patients (MATCH) with new transient ischemic Attack or ischemic affliction trial enrolled patients with late stroke and TIA, 73 percent of whom would be presum to have a high risk of cardiac consequences caused by diabetes or previous myocardial infarction. equal in this population, ischemic blow was five times more likely as an endpoint than myocardial infarction. (5)

Patients with a modern stroke or TIA are at exceedingly high risk for a returning ischemic stroke. Preventing myocardial infarction in these patients is important, still recurrent stroke prevention is paramount, at least for the first brace years. In this context, the make anxious about combined aspirin/extended-release dipyridamole raised at Dr. Solenski should not thwart the use of this therapy in patients with new stroke or TIA.

RICHARD A. BERNSTEIN, MD PHD

Feinberg teach of Medicine of Northwestern University

Abbott Hall, 11th Floor

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REFERENCES

(1) Solenski NJ Transient ischemic attacks: part II. Treatment. Am Fam Physician 2004;69:1681-8

(2) Diener HC Cunha L Forbes C Sivenius J Smet P Lowenthal A. European misfortune Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of rap J Neurol Sci 1996;143:1-13.

(3) Albers GW Choice of endpoints in antiplatelet trials: which issues are most relevant to hit patients? Neurology 2000;54:1022-8.

(4) A randomised, blinded trial of clopidogrel versus aspirin in patients at risk of ischaemic circumstances (CAPRIE). Lancet 1996;348:1329-39.

(5) Diener HC for the MATCH investigators. Management of atherothrombosis with clopidogrel in high-risk patients with modern transient ischemic attack or ischemic hit Paper presented at: 13th European misfortune Conference; May 13, 2004; Mannheim, Germany.

Author disclosure: Dr Bernstein has received honoraria from Boehringer Ingelheim Pharmaceuticals and Bristol-Myers Squibb Company.

IN REPLY: I appreciate the opportunity to address Dr Bernstein's alphabetic character and thank him for his interest in our article. (1) the European rap Prevention Study 2 (ESPS-2) consisted of a large cohort of 6602 patients randomized into four treatment form into groupss with more than 1,600 patients registered in each limb. Primary endpoints were rap death, and stroke and death together. transient ischemic attack (TIA) and other vascular ends were secondary endpoints. More than 33 percent of the patients in each limb had known ischemic heart disease, and an additional 8 percent in each limb had known cardiac failure at the time of enrollment this calculates to more than 500 patients with known ischemic heart disease listed in each limb of the thought An unknown number of patients likely had undiagnosed ischemic heart disease, potentially raising the steady number of patients with cardiac ischemia. Patients were followed in succession treatment with the study mix with drugs for two years. A total of 167 patients experienced myocardial infarction during this time with no statistically significant difference between the thought limbs, particularly between patients receiving aspirin and those receiving placebo. there are hardy data showing that even low-dose aspirin given through short periods of time is cardioprotective. (2) For example, in a cohort of patients with silent ischemia, there is significant benefit from taking low-dose aspirin (75 mg by means of day) as seen in a randomized, double-blind, placebo-controlled trial. (3) the arrange randomized to aspirin had significantly les myocardial infarctions or death at three month compared with the placebo collection (4 versus 21 percent, respectively) and also at 12 month (9 versus 28 percent respectively). therefore, the issue of acetylsalicylic acid on preventing myocardial infarction in this relatively large cohort of patients would be anticipateed however, I agree that myocardial infarction was a secondary issue point and that the trial was not designed to evaluate this. Secondary consequence points still should be analyzed critically because they may provide important data in understanding the representative nature of the patient population being ordealed I strongly agree with Dr Bernstein that results for the evaluation of attack therapies are most accurately determined if attack alone is chosen as the primary endpoint, as was eloquently argued by dint of Dr. Albers. (4) As pointed public in Dr. Albers' article, long-term follow-up studies have institute that after a stroke or TIA, patients have a greater risk of dying of a cardiac fact than of a stroke. (56) this intimates that data on myocardial infarction in the connected thought [i]or[/i] thoughts of the medication being proofed for secondary stroke prophylaxis should continue to be critically analyzed as a secondary result point.