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Randomized Controlled Trial
. 2025 Jul 3;20(7):e0322037.
doi: 10.1371/journal.pone.0322037. eCollection 2025.

Platelet-to-Neutrophil Ratio and Efficacy of Remote Ischemic Conditioning in Acute Ischemic Stroke

Yu Cui  1 , Ling-Yun Cui  1   2 , Xia Chi  2   3 , Qi Wang  1 , Xian-Wen Zhang  4 , Hui-Sheng Chen  1
Affiliations
Randomized Controlled Trial

Platelet-to-Neutrophil Ratio and Efficacy of Remote Ischemic Conditioning in Acute Ischemic Stroke

Yu Cui et al. PLoS One. .

Abstract

Background: Remote ischemic conditioning (RIC) has been proven to improve neurologic function after stroke in RICAMIS trial. Aggravated thrombosis and inflammatory through interaction between platelet and immune cells affected the prognosis of stroke. We conducted an exploratory secondary analysis of RICAMIS to investigate whether platelet-to-neutrophil ratio (PNR) predicted efficacy of RIC in stroke.

Methods: Patients without protocol violation and with baseline blood routine examination from the full analysis set were included and divided into low PNR and high PNR subgroups. The primary outcome was 90-day excellent functional outcome defined as modified Rankin Scale score of 0-1. Compared with usual care alone, we investigated efficacy of RIC treatment in each PNR subgroup and their interaction.

Results: Of 1679 patients, 360 were assigned to low PNR and 1319 into high PNR. Compared with usual care alone, RIC treatment was associated with higher likelihood of 90-day excellent functional outcome across PNR, but significantly different in low PNR (60.9% versus 50.3%, adjusted RD, 11.3%; 95% CI, 1.1% to 21.5%; P =0.03) and not significantly different in high PNR (70.8% versus 65.3%, adjusted RD, 3.9%; 95% CI, -1.2% to 8.9%; P =0.13). No significant interaction was found (P =0.96).

Conclusions: This study firstly investigated the association between PNR at admission and efficacy of RIC treatment in stroke. With respect to long-term functional outcomes, patients benefited from RIC treatment regardless of PNR, but the benefit increased when level of PNR at admission was lower. Trial registration ClinicalTrials.gov Identifier: NCT03740971.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Study Flowchart.
Control group included patients who received usual care based on guideline [23] without RIC treatment. Abbreviations: PNR, platelet to neutrophil ratio; RIC, remote ischemic conditioning; RICAMIS, Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke.
Fig 2
Fig 2. Prediction of PNR for 90-Day Functional Outcome.
(A) Receiver operating characteristic curve for models to predict 90-day excellent functional outcome. The model of RIC included treatment groups, current drinker, and presumed stroke cause. The models of PNR, PMR, PLR, and SⅡ added these ratios based on the model of RIC, respectively. (B) association between PNR at admission and probability of 90-day Excellent Functional Outcome. The likelihood of 90-day excellent functional outcome was across the PNR with (odds ratio, 1.013; 95% confidence interval, 1.008–1.019; P <0.01) and without treatment groups (odds ratio, 1.014; 95% confidence interval, 1.008–1.019; P <0.01). Control group included patients who received usual care based on guideline [23] without RIC treatment. Abbreviations: AUC, area under curve; PLR, platelet to lymphocyte ratio; PMR, platelet to monocyte ratio; PNR, platelet to neutrophil ratio; RIC, remote ischemic conditioning; SⅡ, systemic immune inflammation index.
Fig 3
Fig 3. Distribution of 90-Day mRS Score.
Scores on the mRS range from 0 to 6. 0 = no symptoms, 1 = symptoms without clinically significant disability, 2 = slight disability, 3 = moderate disability, 4 = moderately severe disability, 5 = severe disability, and 6 = death. Control group included patients who received usual care based on guideline [23] without RIC treatment. Abbreviations: mRS, modified Rankin Scale; PNR, platelet to neutrophil ratio; RIC, remote ischemic conditioning.
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