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

Gilliot, Sixtine; Sibon, Igor; Mas, Jean‐Louis; Moulin, Thierry; Béjot, Yannick; Cordonnier, Charlotte; Giroud, Maurice; Odou, Pascal; Bordet, Régis; Vivien, Denis; Leys, Didier

doi:10.1007/s00415-018-8827-6

Cited by 3 publications

(4 citation statements)

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“…Previous studies rarely considered ICH as a major outcome. Recently, Gilliot et al 23 found that on-going treatment with ACE inhibitor or ARBs did not influence hemorrhagic transformation occurrence in a cohort of patients solely treated with intravenous thrombolysis. Of note, in the BP TARGET trial, hemorrhagic transformations consisted of all ICH after EVT, given their deleterious impact on long-term outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, these studies did not assess conventional end points in the acute phase (ie, ICH, National Institutes of Health Stroke Scale [NIHSS] score at 24 hours) and concerned heterogeneous AIS cohorts, with different stroke causes (small vessel disease and large vessel occlusions [LVOs]) with or without reperfusion therapies, limiting the overall relevance of the results. [22][23][24] In this context, we sought to investigate whether prestroke antihypertensive treatments (AHT) categorized as RAS inhibitors or non-RAS inhibitors influenced baseline stroke severity and neurological outcomes, in a homogeneous cohort of patients with AIS due to an anterior LVO and successfully treated by endovascular therapy (EVT).…”

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Effect of Baseline Antihypertensive Treatments on Stroke Severity and Outcomes in the BP TARGET Trial

Maïer

Gory

Lapergue

et al. 2022

Stroke

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Background: Acute ischemic stroke (AIS) patients with a history of hypertension experience worse outcomes, which may be explained by a deleterious impact of the renin-angiotensin system (RAS) overactivation. We sought to investigate whether prestroke antihypertensive treatments (AHT) influenced baseline stroke severity and neurological outcomes, in patients with AIS successfully treated by endovascular therapy. Methods: We performed a post hoc analysis of the BP TARGET trial (Blood Pressure Target in Acute Stroke to Reduce Hemorrhage After Endovascular Therapy) and included hypertensive patients with available data regarding AHT at admission, categorized as RAS inhibitors (ACE [angiotensin-converting enzyme] inhibitors, ARBs [angiotensin 2 receptor blockers], and β-blockers) and non-RAS inhibitors (calcium channel blockers and diuretics). Associations of each AHT with National Institutes of Health Stroke Scale (NIHSS) score at baseline were investigated in linear mixed model adjusted for the number of treatments and center. Associations of each AHT with 24-hour NIHSS change, intracranial hemorrhage were performed using linear mixed model adjusted for baseline NIHSS, the number of treatments, center, age, and sex and adjusted for age, sex, diabetes, and current smoking for favorable outcome. All analyses were performed on cases-available data regarding the low number of missing data. Results: Overall, 203 patients with at least one AHT were included. Patients under non-RAS inhibitor treatments had a higher NIHSS score at baseline (adjusted mean difference=3.28 [95% CI, 1.33–5.22]; P =0.001). Conversely, patients under RAS inhibitor treatments had a lower baseline NIHSS score (adjusted mean difference=−2.81 [95% CI, −5.37 to −0.25]; P =0.031). Intracranial hemorrhage occurrence was significantly more frequent in patients under non-RAS inhibitor treatments (adjusted odds ratio of 2.48 [95% CI, 1.12–5.47]; P =0.025). Conversely, the use of RAS inhibitor treatments before AIS was not associated with higher odds of radiographic intracranial hemorrhage. Patients with non-RAS inhibitor treatments had less improvement of NIHSS at 24 hours compared with patients without (adjusted mean difference, 2.83 [95% CI, −0.16 to 5.81]; P =0.063). Baseline RAS inhibitor or noninhibitor treatments were not associated with favorable outcome. Conclusions: We showed an opposite effect of baseline AHT, based on their effect on the RAS. Patients treated with RAS inhibitor agents before AIS exhibited less severe AIS compared with patients under non-RAS inhibitor treatments, developed less intracranial hemorrhage at 24 hours and had a trend toward better NIHSS score at 24 hours.

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Effect of Baseline Antihypertensive Treatments on Stroke Severity and Outcomes in the BP TARGET Trial

Maïer

Gory

Lapergue

et al. 2022

Stroke

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“…In a randomized controlled trial comparing treatment with the ARB candesartan immediately following stroke or delayed until seven days later (ACCESS trial) there was no significant difference in functional outcome at three months, however early ARB treatment did significantly reduce the number of cardiovascular events [ 230 ]. An observational study of French stroke cohorts demonstrated no benefit of on-going ACEi or ARB treatment on stroke outcomes at 3 months [ 231 ]. However, in contrast to those studied described above, these patients also received thrombolysis with rt-PA. A meta-analysis of 26 clinical trials indicated that ARBs and ACEis offer no BP independent risk reduction for stroke [ 232 ].…”

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The counter regulatory axis of the renin angiotensin system in the brain and ischaemic stroke: Insight from preclinical stroke studies and therapeutic potential

McFall

Nicklin

Work

2020

Cellular Signalling

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Stroke is the 2nd leading cause of death worldwide and the leading cause of physical disability and cognitive issues. Although we have made progress in certain aspects of stroke treatment, the consequences remain substantial and new treatments are needed. Hypertension has long been recognised as a major risk factor for stroke, both haemorrhagic and ischaemic. The renin angiotensin system (RAS) plays a key role in blood pressure regulation and this, plus local expression and signalling of RAS in the brain, both support the potential for targeting this axis therapeutically in the setting of stroke. While historically, focus has been on suppressing classical RAS signalling through the angiotensin type 1 receptor (AT 1 R), the identification of a counter-regulatory axis of the RAS signalling via the angiotensin type 2 receptor (AT 2 R) and Mas receptor has renewed interest in targeting the RAS. This review describes RAS signalling in the brain and the potential of targeting the Mas receptor and AT 2 R in preclinical models of ischaemic stroke. The animal and experimental models, and the route and timing of intervention, are considered from a translational perspective.

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ACE Inhibitors: Preferred RAAS Inhibitor in High-Risk Patients as Compared to ARBs

Nandave

2024

Angiotensin-Converting Enzyme Inhibitors vs. Angiotensin Receptor Blockers

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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

Abstract: 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.

Cited by 3 publications

References 13 publications

Effect of Baseline Antihypertensive Treatments on Stroke Severity and Outcomes in the BP TARGET Trial

Effect of Baseline Antihypertensive Treatments on Stroke Severity and Outcomes in the BP TARGET Trial

The counter regulatory axis of the renin angiotensin system in the brain and ischaemic stroke: Insight from preclinical stroke studies and therapeutic potential

ACE Inhibitors: Preferred RAAS Inhibitor in High-Risk Patients as Compared to ARBs

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