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. 2024 Jul 1;7(7):e2423677.
doi: 10.1001/jamanetworkopen.2024.23677.

Disability and Recurrent Stroke Among Participants in Stroke Prevention Trials

Adam de Havenon  1 , Catherine Viscoli  2 , Dawn Kleindorfer  3 , Heidi Sucharew  4 , Alen Delic  5 , Christopher Becker  3 , David Robinson  3 , Shadi Yaghi  6 , Vivian Li  1 , Maarten G Lansberg  7 , Steven C Cramer  8 , Eva A Mistry  9 , Daniel F Sarpong  2 , Scott E Kasner  10 , Walter Kernan  2 , Kevin N Sheth  1
Affiliations

Disability and Recurrent Stroke Among Participants in Stroke Prevention Trials

Adam de Havenon et al. JAMA Netw Open. .

Abstract

Importance: Stroke secondary prevention trials have disproportionately enrolled participants with mild or no disability. The impact of this bias remains unclear.

Objective: To investigate the association between poststroke disability and the rate of recurrent stroke during long-term follow up.

Design, setting, and participants: This cohort study is a post hoc analysis of the Prevention Regimen For Effectively Avoiding Second Strokes (PRoFESS) and Insulin Resistance Intervention After Stroke (IRIS) secondary prevention clinical trial datasets. PRoFESS enrolled patients from 2003 to 2008, and IRIS enrolled patients from 2005 to 2015. Data were analyzed from September 23, 2023, to May 16, 2024.

Exposure: The exposure was poststroke functional status at study baseline, defined as modified Rankin Scale (mRS; range, 0-5; higher score indicates more disability) score of 0 vs 1 to 2 vs 3 or greater.

Main outcomes and measures: The primary outcome was recurrent stroke. The secondary outcome was major cardiovascular events (MACE), defined as recurrent stroke, myocardial infarction, new or worsening heart failure, or vascular death.

Results: A total of 20 183 PRoFESS participants (mean [SD] age, 66.1 [8.5] years; 12 931 [64.1%] male) and 3265 IRIS participants (mean [SD] age, 62.7 [10.6] years; 2151 [65.9%] male) were included. The median (IQR) follow-up was 2.4 (1.9-3.0) years in PRoFESS and 4.7 (3.2-5.0) years in IRIS. In PRoFESS, the recurrent stroke rate was 7.2%, among patients with an mRS of 0, 8.7% among patients with an mRS of 1 or 2, and 10.6% among patients with an mRS of 3 or greater (χ22 = 27.1; P < .001); in IRIS the recurrent stroke rate was 6.4% among patients with an mRS of 0, 9.0% among patients with an mRS of 1 or 2, and 11.7% among patients with an mRS of 3 or greater (χ22 = 11.1; P < .001). The MACE rate was 10.1% among patients with an mRS of 0, 12.2% among patients with an mRS of 1 or 2, and 17.2% among patients with an mRS of 3 or greater (χ22 = 103.4; P < .001) in PRoFESS and 10.9% among patients with an mRS of 0, 13.3% among patients with an mRS of 1 or 2, and 15.3% among patients with an mRS of 3 or greater (χ22 = 5.8; P = .06) in IRIS. Compared with patients with an mRS of 0, patients with an mRS of 3 or greater had increased hazard for recurrent stroke in PRoFESS (hazard ratio [HR], 1.63; 95% CI, 1.38-1.92; P < .001) and in IRIS (HR, 1.91; 95% CI, 1.28-2.86; P = .002). There was also increased hazard for MACE in PRoFESS (HR, 1.90; 95% CI, 1.66-2.18; P < .001) and in IRIS (HR, 1.45; 95% CI, 1.03-2.03; P = .03).

Conclusions and relevance: This cohort study found that higher baseline poststroke disability was associated with increased rates of recurrent stroke and MACE. Including more patients with greater baseline disability in stroke prevention trials may improve the statistical power and generalizability of these studies.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr de Havenon reported receiving personal fees from Integra, Novo Nordisk and UpToDate and owning equity in TitinKM and Certus. Dr Kleindorfer reported receiving personal fees from Bayer outside the submitted work. Dr Cramer reported receiving personal fees from AbbVie, Constant Therapeutics, BrainQ, Myomo, MicroTransponder, Neurolutions, Panaxium, NeuExcell, Elevian, Helius, Omniscient, Brainsgate, Nervgen, Battelle, and TRCare outside the submitted work. Dr Mistry reported receiving grants from National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke (NINDS) and Patient-Centered Outcomes Research Institute and personal fees from AbbVie, Silvercreek Pharmaceuticals, RAPID AI, and Translational Sciences outside the submitted work. Dr Kasner reported receiving grants from Bayer, Bristol-Myers Squibb, Diamedica, and WL Gore outside the submitted work. Dr Sheth reported receiving grants from NIH and American Heart Association; personal fees from Hyperfine, Astrocyte, Cerovasc, Sense, Bexorg, Zoll, Rhaeos, and CSL Behring; and owning equity in Alva outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Kaplan-Meier Curves for Recurrent Stroke Events and Major Cardiovascular Events (MACE) in the Prevention Regimen for Effectively Avoiding Second Strokes Trial Cohort, Stratified by Poststroke Categories of the Modified Rankin Scale (mRS)
See this image and copyright information in PMC

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