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Randomized Controlled Trial
. 2024 Sep;47(9):2238-2249.
doi: 10.1038/s41440-024-01742-3. Epub 2024 Jul 9.

Blood pressure during long-term cilostazol-based dual antiplatelet therapy after stroke: a post hoc analysis of the CSPS.com trial

Kazunori Toyoda  1 , Masatoshi Koga  2 , Kenta Tanaka  3 , Shinichiro Uchiyama  4 , Hisato Sunami  5 , Katsuhiro Omae  3   5 , Kazumi Kimura  6 , Haruhiko Hoshino  7 , Mayumi Fukuda-Doi  2   3 , Kaori Miwa  2 , Junpei Koge  2 , Yasushi Okada  8 , Nobuyuki Sakai  9 , Kazuo Minematsu  10 , Takenori Yamaguchi  2 ; CSPS.com Trial Investigators
Collaborators, Affiliations
Randomized Controlled Trial

Blood pressure during long-term cilostazol-based dual antiplatelet therapy after stroke: a post hoc analysis of the CSPS.com trial

Kazunori Toyoda et al. Hypertens Res. 2024 Sep.

Abstract

We determined the associations of follow-up blood pressure (BP) after stroke as a time-dependent covariate with the risk of subsequent ischemic stroke, as well as those of BP levels with the difference in the impact of long-term clopidogrel or aspirin monotherapy versus additional cilostazol medication on secondary stroke prevention. In a sub-analysis of a randomized controlled trial (CSPS.com), patients between 8 and 180 days after stroke onset were randomly assigned to receive aspirin or clopidogrel alone, or a combination of cilostazol with aspirin or clopidogrel. The percent changes, differences, and raw values of follow-up BP were examined. The primary efficacy outcome was the first recurrence of ischemic stroke. In a total of 1657 patients (69.5 ± 9.3 years, female 29.1%) with median 1.5-year follow-up, ischemic stroke recurred in 74 patients. The adjusted hazard ratio for ischemic stroke of a 10% systolic BP (SBP) increase from baseline was 1.19 (95% CI 1.03-1.36), that of a 10 mmHg SBP increase was 1.14 (1.03-1.28), and that of SBP as the raw value with the baseline SBP as a fixed (time-independent) covariate was 1.14 (1.00-1.31). Such significant associations were not observed in diastolic BP-derived variables. The estimated adjusted hazard ratio curves for the outcome showed the benefit of dual therapy over a wide SBP range between ≈120 and ≈165 mmHg uniformly. Lower long-term SBP levels after ischemic stroke were associated with a lower risk of subsequent ischemic events. The efficacy of dual antiplatelet therapy including cilostazol for secondary stroke prevention was evident over a wide SBP range.

Keywords: Antiplatelet therapy; Cerebral infarction; Cilostazol; Hypertension; Stroke prevention.

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Conflict of interest statement

All of the following are outside the submitted work. Toyoda reports honoraria from Otsuka Pharmaceutical, Daiichi-Sankyo, Bristol-Myers-Squibb, Bayer Yakuhin, and Janssen. Koga reports honoraria from Bayer Yakuhin, Daiichi-Sankyo, Mitsubishi Tanabe Pharma Corporation, and research support from, Daiichi-Sankyo, Nippon Boehringer Ingelheim. Hoshino reports honoraria from Otsuka Pharmaceutical, Bristol-Myers-Squibb and Pfizer. Okada reports honoraria from Daiichi-Sankyo and Pfizer. Sakai reports a research grant from Biomedical Solutions, Medtronic, Terumo and TG Medical; lecturer’s fees from Asahi-Intec, Biomedical Solutions, Daiichi Sankyo, Kaneka, Medtronic, Stryker and Terumo; and membership on the advisory boards for Johnson & Johnson, Medtronic and Terumo. Minematsu reports honoraria from Bayer Yakuhin and Pfizer. None of the other authors have any conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Trial profile
Fig. 2
Fig. 2
Blood pressure at each visit
Fig. 3
Fig. 3
Hazard ratio curve of the dual therapy group versus the monotherapy group. A Ischemic stroke, B a composite of stroke, myocardial infarction, and vascular death. Adjusted by sex, age, assigned treatment, antiplatelet agents at randomization, intracranial artery stenosis, and the time of starting trial treatment
See this image and copyright information in PMC

Comment in

References

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