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(Stroke. 2004;35:2238-a.)
© 2004 American Heart Association, Inc.

Letters to the Editor

"Lacunarization" of Stroke Prevention Studies

Seemant Chaturvedi, MD

Department of Neurology and Stroke Program, Wayne State University, Detroit, Mich

Key Words: anticoagulantsplatelet aggregation

To the Editor:

Recent stroke prevention studies that have compared differing antithrombotic regimens have been somewhat disappointing in that the more intense antithrombotic regimen has failed to demonstrate superiority over the more conservative regimen. Although this may reflect the fact that established therapy is difficult to improve on,¹ I am concerned that the stroke subtype composition in these trials may be distorting the outcome and that they are not reflective of the larger community of patients with ischemic stroke.

As examples, in the Warfarin Aspirin Recurrent Stroke Study, the lacunar infarct patients represented 56.1% of the study cohort.² In the African-American Antiplatelet Stroke Prevention Study, the small vessel infarct subtype accounted for 67.5% of patients.³ Finally, in the recently reported Management of Atherothrombosis With Clopidogrel in High-Risk Patients Study, 52.5% of patients had lacunar infarcts as the qualifying subtype.⁴

Thus, to some extent, each of these studies could be viewed as a referendum on lacunar infarction treatment. In a study that excluded cardioembolic strokes, one would expect that 40% of patients would have cryptogenic infarcts, and 30% should have large vessel atherosclerotic and lacunar infarcts. The fact that recent studies are enrolling >50% of the study population as lacunar infarction patients does not seem representative of the larger spectrum of ischemic stroke patients. It also impairssubgroup comparison and hypothesis generation for future studies of large vessel atherosclerotic and cryptogenic infarction.

Clinical trialists who design future studies of "noncardioembolic stroke" should consider limiting lacunar infarct enrollment to 30% of the study cohort and should try to avoid making the entry criteria overly restrictive so that only patients with minimal disability (who tend to be those with lacunar stroke) are allowed in the trial.

References

1. Anderson DC, Goldstein LB. Aspirin: it’s hard to beat. Neurology. 2004; 62: 1036–1037.[Free Full Text]
2. Mohr JP, Thompson JL, Lazar RM, Levin B, Sacco RL, Furie KL, Kistler JP, Albers GW, Pettigrew LC, Adams HP Jr, Jackson CM, Pullicino P; Warfarin-Aspirin Recurrent Stroke Study Group. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med. 2001; 345: 1444–1451.[Abstract/Free Full Text]
3. Gorelick PB, Richardson D, Kelly M, Ruland S, Hung E, Harris Y, Kittner S, Leurgans S; African-American Antiplatelet Stroke Prevention Study Investigators. Aspirin and ticlopidine for prevention of recurrent stroke in black patients: a randomized trial. J Am Med Assoc. 2003; 289: 2947–2957.[Abstract/Free Full Text]
4. Brass, LM. Management of ATherothrombosis with Clopidogrel in High-risk patients with recent TIA or ischemic stroke. Paper presented at: the European Stroke Conference; May 12–15, 2004; Mannheim-Heidelberg, Germany.

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