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Influence of on-going treatment with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker on the outcome of patients treated with intravenous rt-PA for ischemic stroke

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Abstract

Background

Many patients who receive intravenous (i.v.) recombinant tissue-plasminogen activator (rt-PA) for acute cerebral ischemia were under angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) at stroke onset. ACE-Is and ARBs have neuroprotective properties in animal models.

Objective

To evaluate whether the 3-month outcome of patients treated with i.v. rt-PA for cerebral ischemia was influenced by on-going therapy with ACE-Is or ARBs.

Method

This study was observational, conducted in two prospective registries of stroke patients treated with i.v. rt-PA. We evaluated outcomes with the modified Rankin scale and symptomatic intracranial hemorrhages (s-ICH) according to the ECASS2 criteria. We compared outcomes between patients with and without ACE-Is/ARBs according to the modified Rankin scale (mRS) at month 3, using logistic regression analyses adjusted on propensity scores, and propensity-matched analyses.

Results

Of 1803 patients, 455 (25.2%) were under ACE-Is (259), ARBs (188) or both (8). At 3 months, patients under ACE-Is or ARBs were more likely to have an mRS 0–1, but did not differ for mRS 0–2, s-ICH and death. After adjustment on propensity scores, the association between ACE-Is/ARBs and mRS 0–1 disappeared. The propensity-matched analysis, performed in 397 pairs of patients, found no difference in outcomes between patients with and without ACE-Is or ARBs.

Conclusion

In patients treated by intravenous thrombolytic therapy for ischemic stroke, on-going treatment with ACE-Is or ARBs does not influence on outcomes after adjustment on baseline characteristics and propensity scores.

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Acknowledgements

Co-investigators of OPHELIE: All co-investigators who are not authors of the manuscript contributed by the clinical evaluation of patients at admission, or during follow-up. Those who meet criteria for authorship are not listed below. Agnes Jacquin-Piques, MD (univ-Dijon, site investigator); Anais Daumas, MD (univ-Dijon, site investigator); Anne-Marie Mendyk, RN (CHU Lille, study manager); Anthony Faivre, MD, PhD (Ste Anne Military Teaching Hospital, Toulon, site investigator); Arnaud Chevilley, PhD (Inserm, Inserm UMR-S 919, University Caen-Normandie, GIP Cyceron, Caen, site investigator); Aude Triquenot-Bagan, MD (Rouen University Hospital, site investigator); Benoit Daubail, MD (univ-Dijon, site investigator); Camille Potey PharmD (univ-Lille, INSERM U1171, CHU Lille, site investigator); Catherine Lamy, MD (University Paris Descartes, Sorbonne Paris Cité, INSERM UMR S894, Sainte-Anne Hospital, DHU NeuroVasc, site investigator); Cécile Gréaud, MD (University Paris Descartes, Sorbonne Paris Cité, INSERM UMR S894, Sainte-Anne Hospital, DHU NeuroVasc, site investigator); Chantal Lamy, MD (Amiens University Hospital, site investigator); Clémence Jacquet, MD (CHU Lille, site investigator); Costanza Rossi, MD (CHU Lille, site investigator); David Calvet, MD (University Paris Descartes, Sorbonne Paris Cité, INSERM UMR S894, Sainte-Anne Hospital, DHU NeuroVasc, site investigator); Elisabeth Medeiros de Bustos, MD (University of Franche Comté, CHU Besançon, site investigator); Flavie Lesept, PhD (Inserm, Inserm UMR-S 919, University Caen-Normandie, GIP Cyceron, Caen, site investigator); Francisco Macian Montoro, MD (University Hospital of Limoges, site investigator); Francoise Kestens. MD (Rennes University Hospital, site investigator); Guillaume Turc, MD (University Paris Descartes, Sorbonne Paris Cité, INSERM UMR S894, Sainte-Anne Hospital, DHU NeuroVasc, site investigator); Hilde Hénon, MD, PhD (INSERM U1171, CHU Lille, site investigator); Jean François Pinel, MD (Rennes University Hospital, site investigator); Jean-Michel Vallat, MD, PhD (University Hospital of Limoges, site investigator); Katia Garambois, MD (Univ. Grenoble Alpes, site investigator); Laurent Lebouvier, PhD (Inserm, Inserm UMR-S 919, University Caen-Normandie, GIP Cyceron, Caen, site investigator); Loubna Majhadi, MD (University Paris Descartes, Sorbonne Paris Cité, INSERM UMR S894, Sainte-Anne Hospital, DHU NeuroVasc, site investigator); Marianne Barbieux, MD (Univ. Grenoble Alpes, site investigator); Marie Bodenant, MD, MSc (CHU Lille, site investigator); Marie Bruandet, MD (University Hospital Paris St Joseph Paris, site investigator); Marina Rubio PhD (Inserm, Inserm UMR-S 919, University Caen-Normandie, GIP Cyceron, Caen, site investigator); Mathieu Zuber, MD, PhD (University Hospital Paris St Joseph Paris, site investigator); Mathilde Poli, MD (University of Bordeaux, Bordeaux University Hospital, site investigator); Nelly Dequatre-Ponchelle, MD, MSc (CHU Lille, site investigator); Nicolas Legris, MD (univ-Dijon, site investigator); Olivier Detante, MD, PhD (CHU Grenoble, site investigator); Ozlem Ozkul-Wermester, MD (Rouen University Hospital, site investigator); Pascal Favrole, MD (University Hospital Paris Tenon, site investigator); Pauline Renou, MD (University of Bordeaux, Bordeaux University Hospital, site investigator); Sabrina Debruxelles, MD (University of Bordeaux, Bordeaux University Hospital, site investigator); Sharmila Sagnier, MD (University of Bordeaux, Bordeaux University Hospital, site investigator); Solène Moulin, MD, MSc (CHU Lille, site investigator); Sonia Alamowitch. MD, PhD (University Hospital Paris Tenon, site investigator); Sophie Lenoir, PhD (Inserm, Inserm UMR-S 919, University Caen-Normandie, GIP Cyceron, Caen, site investigator); Stéphane Vannier, MD (Rennes University Hospital, site investigator); Thavarak Ouk, PharmD, PhD (univ-Lille, INSERM U1171, CHU Lille, site investigator); Thomas Ronzière, MD (Rennes University Hospital, site investigator); Valentin Vergriete, MSc (univ-Lille, INSERM U1171, CHU Lille), study manager; Valérie Domigo, MD (University Paris Descartes, Sorbonne Paris Cité, INSERM UMR S894, Sainte-Anne Hospital, DHU NeuroVasc, site investigator); Veronica Lassalle, MD (Rennes University Hospital, site investigator); Yannick Hommet PhD (Inserm, Inserm UMR-S 919, University Caen-Normandie, GIP Cyceron, Caen, site investigator).

We thank all the investigators who recruited patients in the OPHELIE [5] study and in the Lille Stroke Thrombolysis registry [6]. Their names and affiliations are detailed in the corresponding articles [5, 6].

Funding

OPHELIE was supported by grants from the INSERM (French National Institute for Health and Medical Research, Inserm UMR-S U1171 and U919), University of Lille, Lille University Hospital, Adrinord, University Caen-Normandie, FP7 Eranet-NEURON 3-275-006, Team FRM N°DEQ 20140329555, Ministry of Health (Strokavenir Network, PHRC grant). Alicante had made available the e-CRF.

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Correspondence to Didier Leys.

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Conflicts of interest

Jean-Louis Mas, Charlotte Cordonnier, and Didier Leys are investigators of ECASS4 (no honoraria). Didier Leys has been member of scientific advisory boards and symposia for Boehringer-Ingelheim (fees paid to ADRINORD). Sixtine Gilliot, Igor Sibon, Thierry Moulin, Yannick Bejot, Maurice Giroud, Pascal Odou, Régis Bordet, and Denis Vivien, declare no conflict of interest.

Ethical approval

The study was approved by French health authorities and by the relevant ethical committee (Comité de Protection des Personnes Nord Ouest IV Lille, France) by March 9th, 2010, under registration number 10.677.

Informed consent

Patients gave informed consent themselves or via a close relative.

Additional information

The OPHELIE Investigators are listed in the Acknowledgements section.

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Gilliot, S., Sibon, I., Mas, JL. et al. Influence of on-going treatment with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker on the outcome of patients treated with intravenous rt-PA for ischemic stroke. J Neurol 265, 1166–1173 (2018). https://doi.org/10.1007/s00415-018-8827-6

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  • DOI: https://doi.org/10.1007/s00415-018-8827-6

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