Impact Of Renin-angiotensin System Inhibitors Research Articles

Impact of Renin-Angiotensin System Blockade on Mortality and Allograft Loss among Renal Transplant Recipients: A Systematic Review and Meta-Analysis.

The blockade of the renin-angiotensin system (RAS) has a beneficial effect on reducing the levels of proteinuria and blood pressure in patients with chronic kidney disease (CKD) and reduces the risk of developing end-stage kidney disease in CKD patients. Nonetheless, a debate persists regarding the impact of RAS inhibitors on outcomes such as mortality and graft survival in renal transplant patients. To assess the effect of RAS inhibitors on graft recipients in the past decade, we conducted a systematic review and meta-analysis. We searched Embase, PubMed, and the Cochrane Central Register of Clinical Trials from January 1, 2012, to August 1, 2022. We included 14 articles, comprising 5 randomized controlled trials (RCTs) and 9 cohort studies, including 45,377 patients. These studies compared patient or graft survival between an RAS inhibitor treatment arm and a control arm. The meta-analysis revealed that RAS blockade was significantly associated with lower mortality in cohort studies (risk ratio [RR] = 0.66, 95% confidence interval [CI]: 0.55-0.79), reduced allograft loss in cohort studies (RR = 0.62, 95% CI: 0.54-0.71), and significant changes in systolic blood pressure in RCTs. Subgroup analysis of the groups of interest (interventions involving RAS blockade, follow-up period of ≥5 years) showed consistently reduced mortality (RR = 0.67, 95% CI: 0.56-0.81) and reduced allograft loss (RR = 0.61, 95% CI: 0.54-0.70). Our results demonstrated that the application of RAS blockade among renal transplant recipients was associated with lower mortality and allograft loss in cohort studies but not in RCTs. More powered clinical trials are needed to evaluate the effects of RAS blockade in renal transplant recipients.

The potential impact of renin-angiotensin system inhibitors on cancer survival and recurrence: A systemic review and meta-analysis.

Renin-angiotensin-system inhibitors (RASi), specifically angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs), are widely used anti-hypertensives. Their impact on the prognostic outcomes among cancer patients has been subject to scrutiny and debate. The aim of this study is to evaluate the effect of RASi on survival in cancer patients. We systematically searched PubMed, Web of Science, Embase and Cochrane Library for relevant studies published until April 1st, 2022. All the studies, interventional or observational, which examined effects of ARBs and ACEi on cancer prognosis compared to a control group and reported the survival outcomes and Hazards Ratios were included in the analysis. From each study, pooled hazard ratios (HR) with corresponding 95% confidence intervals (95% CI) were identified and collected. Subgroup analysis was conducted to investigate heterogeneity. Sixty-one studies were included in this meta-analysis. Data of 343,283 participants were used in the study. It was found that RASi improved overall survival (OS) (HR=0.88; 95% CI: 0.82-0.93; P<0.0001), progression free survival (PFS) (HR=0.72; 95% CI: 0.65-0.79; P<0.00001), disease specific survival (DSS) (HR=0.86; 95% CI: 0.71-1.04; P=0.03), and recurrence free survival (RFS) (HR=0.74; 95% CI: 0.58-0.93; P=0.01) in cancer patients. The effect of RASi on OS varied depending on the type of cancer or type of RASi (ACEi or ARBs), according to subgroup analysis. The usage of RAS inhibitors has a positive impact on survival outcomes and recurrence among cancer patients.

Dose and Time Effects of Renin-Angiotensin Inhibitors on Patients With Advanced Stages 4 to 5 of Diabetic Kidney Disease.

Limited evidence exists regarding the cumulative dosing and duration impact of renin-angiotensin system inhibitors (RASis) on cardiorenal and mortality outcomes in patients with advanced stages (predominantly in stage 5 and a minority in stage 4) of diabetic kidney disease (DKD). To retrospectively investigate whether there are dose- and time-dependent relationships between RASis and cardiorenal and mortality outcomes in this population. Using Taiwan's national health insurance data in 2000-2017, we analyzed 2196 RASi users and 2196 propensity-matched nonusers among 8738 patients living with diabetes and newly diagnosed with advanced chronic kidney disease (23% stage 4, 77% stage 5). Cox proportional hazards regression models were used to estimate adjusted hazard ratios (aHRs) and 95% CI. RASi use was significantly associated with reduced risks of all-cause mortality (aHR, 0.53; 95% CI 0.47-0.60) and cardiovascular mortality (0.68; 0.56-0.83) with the degree of benefit depending on therapeutic dosage and duration, despite a nonsignificant increase in acute kidney injury risk (1.16; 0.98-1.38) and a significant increase in hyperkalemia risk (1.45; 1.19-1.77). Significant differences in proteinuria risk (1.32; 1.21-1.43) were observed, while there were no significant differences in end-stage renal disease risk (1.01; 0.88-1.15) and no dose- or time-response relationships for either end-stage renal disease or proteinuria risks. Sensitivity analyses confirmed cardiovascular and survival benefits, even in patients with stage 5 DKD. This real-world study suggests that RASi use in advanced stages 4 to 5 DKD may provide dose- and time-dependent cardioprotection and improved survival, without excess renal harms.

Concomitant use of renin-angiotensin system inhibitors augments the efficacy of immune checkpoint inhibitors: a systematic review and meta-analysis.

The impact of renin-angiotensin system inhibitors (RASIs) on the outcome of hypertensive cancer patients undergoing immune checkpoint inhibitor (ICIs) therapy remains ambiguous. This investigation sought to elucidate the consequences of RASIs use on the prognosis for this specific patient group within the context of ICIs treatment, aspiring to provide a clearer basis for rational, evidence-driven choices in the clinical prescription of these medications. A comprehensive search was conducted on PubMed, Embase, Web of Science, and the Cochrane Library for original studies published up to 6 August 2023. Studies published in English reporting hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and/or progression-free survival (PFS) were included. All statistical analyses were executed utilizing R software (version 4.2.2). A total of 13 studies, encompassing approximately 12,595 patients, satisfied the inclusion criteria. Meta-analyses demonstrated a statistically significant association between the use of RASIs and a favorable outcome in OS (HR, 0.74; 95% CI, 0.62-0.88) and PFS (HR, 0.77; 95% CI, 0.62-0.96) among cancer patients receiving ICIs treatment. This investigation provides compelling evidence supporting the beneficial prognostic impact of RASIs on cancer patients receiving ICIs. RASIs present a viable option as antihypertensive agents for cancer patients with hypertension undergoing ICIs treatment. Further exploration and validation through prospective studies are necessary to establish definitive guidelines for the use of RASIs in managing hypertensive cancer patients undergoing immunotherapy with ICIs. https://www.crd.york.ac.uk/prospero/, identifier CRD42023454886.

Impact of renin-angiotensin system inhibitors on response to PD1/L1 inhibitors in patients with metastatic renal cell carcinoma (mRCC).

Impact of renin-angiotensin system inhibitors on response to PD1/L1 inhibitors in patients with metastatic renal cell carcinoma (mRCC).

Long-Term Impact of Renin-Angiotensin System Inhibitors for Secondary Prevention in Patients with Chronic Kidney Disease Who Underwent Percutaneous Coronary Intervention

Introduction: The long-term impact of renin-angiotensin system (RAS) inhibitors for secondary prevention in patients with chronic kidney disease (CKD) and coexisting coronary artery disease remains unclear. Methods: Altogether, 1,160 consecutive patients with CKD (mean age, 70 ± 9 years; 78% men) who underwent their first percutaneous coronary intervention (PCI) between 2000 and 2018 were included and analyzed. Based on their RAS inhibitor use, 674 patients (58%) were allocated to the RAS inhibitor group, and 486 patients (42%) were allocated to the non-RAS inhibitor group. This study evaluated the incidence of 3-point major adverse cardiovascular events (3P-MACE), including cardiovascular death, nonfatal acute coronary syndrome and nonfatal stroke, admission for heart failure (HF), target vessel revascularization (TVR), and all-cause death. Results: During a median follow-up duration of 7.8 years, 280 patients (24.1%) developed 3P-MACE, 134 patients (11.6%) were hospitalized for HF, 171 patients (14.7%) underwent TVR, and 348 patients (30.0%) died of any causes. The cumulative incidence rate of 3P-MACE in the RAS inhibitor group was significantly lower than in the non-RAS inhibitor group (31.7% vs. 39.0%, log-rank test, p = 0.034); however, that of admission for HF in the RAS inhibitor group was significantly higher than in the non-RAS inhibitor group (28.1% vs. 13.3%, log-rank test, p < 0.001). The subgroup of preserved ejection fraction, non-acute myocardial infarction, and non-proteinuria tended to promote the onset of HF rather than cardiovascular prevention by RAS inhibitors. Conclusion: The long-term RAS inhibitor use for patients with CKD after PCI might prevent cardiovascular events but increase the risk of HF.

Abstract 6755: The impact of renin-angiotensin system inhibitors on survival outcomes of pancreatic adenocarcinoma patients

Abstract Introduction Pancreatic adenocarcinoma (PDAC) is a highly aggressive malignancy with significant morbidity and mortality. RAS (renin-angiotensin system) inhibitors have been used for hypertension, and the potential role of using RAS inhibitors in pancreatic adenocarcinoma have been investigated in pre-clinical models by enhancing drug delivery and reducing hypoxia. However, the clinical benefit of RAS inhibitors in pancreatic cancer patients was still unclear. Methods We retrospectively investigated the impact of RAS inhibitors on survival outcomes of pancreatic adenocarcinoma patients in Taichung Veterans General Hospital between January 2014 and July 2021. Patients with histologically proven pancreatic adenocarcinoma were included in the study. Clinical feature with drugs exposure and survival outcome were analyzed. Results A total of 384 pancreatic cancer patients were analyzed. Among them, 70 patients had concurrent use of RAS inhibitors and 314 patients had no concurrent medication use. Among patients with RAS inhibitors use, the diagnosed age was significantly older (70.0 vs. 68.0, p = 0.023), and a higher proportion of hypertension (100.0% vs. 51.0%, p &amp;lt; 0.0001), chronic kidney disease (27.5% vs. 9.1%, p &amp;lt; 0.0001), and diabetes (64.3% vs 39.5%, p &amp;lt; 0.0001) than those without RAS inhibitors use. The 12-month progression-free survival were 22.9% and 13.7% in the RAS inhibitors and control group (p = 0.008), respectively. The Overall survival was not significantly different in the both groups (p = 0.356). In the multivariate analysis, the use of RAS inhibitors had a significantly better progression-free survival outcome (Hazard ratio = 0.025, CI:0.52-0.96). The advanced disease status, poor ECOG performance status and the elevated level of CA19-9 were correlated with poor progression-free survival. Conclusion In our study, although higher percentage of existed comorbidities in the RAS inhibitor group, we demonstrated that the use of RAS inhibitors among pancreatic cancer patients might provide a better progression-free survival outcome. Further prospective study and investigation are warranted. Citation Format: Kuan-Yu Tseng, Cheng-Wei Chou. The impact of renin-angiotensin system inhibitors on survival outcomes of pancreatic adenocarcinoma patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6755.

Robust causal inference of drug-drug interactions.

There is growing interest in developing causal inference methods for multi-valued treatments with a focus on pairwise average treatment effects. Here we focus on a clinically important, yet less-studied estimand: causal drug-drug interactions (DDIs), which quantifies the degree to which the causal effect of drug A is altered by the presence versus the absence of drug B. Confounding adjustment when studying the effects of DDIs can be accomplished via inverse probability of treatment weighting (IPTW), a standard approach originally developed for binary treatments and later generalized to multi-valued treatments. However, this approach generally results in biased results when the propensity score model is misspecified. Motivated by the need for more robust techniques, we propose two empirical likelihood-based weighting approaches that allow for specifying a set of propensity score models, with the second method balancing user-specified covariates directly, by incorporating additional, nonparametric constraints. The resulting estimators from both methods are consistent when the postulated set of propensity score models contains a correct one; this property has been termed multiple robustness. In this paper, we derive two multiply-robust estimators of the causal DDI, and develop inference procedures. We then evaluate their finite sample performance through simulation. The results demonstrate that the proposed estimators outperform the standard IPTW method in terms of both robustness and efficiency. Finally, we apply the proposed methods to evaluate the impact of renin-angiotensin system inhibitors (RAS-I) on the comparative nephrotoxicity of nonsteroidal anti-inflammatory drugs (NSAID) and opioids, using data derived from electronic medical records from a large multi-hospital health system.

Impact of renin-angiotensin system inhibitors on outcomes in patients with metastatic renal cell carcinoma treated with immune-checkpoint inhibitors.

Renin-angiotensin system inhibitors (RASi) have been shown to improve outcomes in studies of multiple malignancies by effects on the tumor microenvironment to enhance the immune repertoire and improve drug delivery. Repurposing RASi to treat metastatic renal cell carcinoma (mRCC) in combination with immune-checkpoint inhibitors (ICI) may improve survival coupled with tolerability and cost efficacy. We evaluated the impact of RASi on outcomes in mRCC patients receiving ICI. This multicenter, retrospective cohort study included mRCC patients treated with ICI with or without RASi. The patients from Dana-Farber Cancer Institute (DFCI) were used as a discovery cohort, and the patients from University of California San Diego (UCSD) were used for validation. Receipt of an ICI (PD1/L1 and/or CTLA-4 inhibitors) was required. RASi use was defined as receipt of a RASi at baseline and for a minimum of 30 days after ICI initiation. For both the discovery and validation cohorts, the primary outcome assessed was overall survival (OS) and the secondary endpoints were time-to-treatment failure (TTF), and objective response rate (ORR). Overall, 229 patients who received an ICI were included: 100 patients from DFCI and 129 patients from UCSD. Concomitant RASi were administered in 30 patients (30%) in the DFCI cohort and 59 (45%) in the UCSD cohort. Median age at ICI initiation was 62.5 years in both cohorts. Median follow-up was 3.8 [IQR 3-5.3] years in the DFCI cohort, and 2.3 [IQR 1.4-3.6] years in the UCSD cohort. In the DFCI cohort, RASi was significantly associated with longer OS (adjusted-HR 0.35 [95% CI, 0.17-0.70], P=.003) and TTF (adjusted-HR 0.57 [0.36-0.92], P=.02). In the validation cohort, RASi was associated with TTF (adjusted HR, 0.60 [0.39-0.92], P=.02) and not statistically associated with OS (adjusted-HR 0.60 [0.34-1.06], P = .07). The propensity analysis, matching 83 patients from both cohorts receiving RASi while on ICI with 83 who did not, showed that RASi significantly improved OS (HR 0.59 [0.37-0.95], P=.03) and TTF (HR 0.60 [0.43-0.85], P=.0034). RASi was associated with improved OS and TTF in mRCC patients receiving ICI. This provides a rationale for prospective randomized studies combining ICI and RASi in mRCC patients.

Impact of renin-angiotensin system inhibitors on the survival of patients with rectal cancer

BackgroundRenin-angiotensin system inhibitors (RASIs) are widely used in the treatment of hypertension. However, their impact on the outcome of the combined treatment of rectal cancer is poorly understood. The aim of this study was to assess the effect of RASIs on the survival of rectal cancer patients with associated hypertension after neoadjuvant treatment and radical resection.MethodsBetween 2008 and 2016, 242 radical (R0) rectal resections for cancer were performed after neoadjuvant treatment in patients with associated hypertension. At the time of treatment, 158 patients were on RASIs, including 35 angiotensin-receptor antagonists (ARB) users and 123 angiotensin-converting enzyme inhibitors (ACEI) users. Eighty-four patients were on drugs other than RASIs (non-RASI users). The survival analysis was performed using the Kaplan–Meier estimator with the log-rank test and the Cox proportional hazards model.ResultsThe log-rank test showed a significantly worse overall survival (OS) in the group of ACEI users compared to ARB users (p = 0.009) and non-RASI users (p = 0.013). Disease-free survival (DFS) was better in the group of ARB users compared to ACEI users. However, the difference was not statistically significant (p = 0.064). The Multivariate Cox analysis showed a significant beneficial effect of ARBs on OS (HR: 0.326, 95% CI: 0.147–0.724, p = 0.006) and ARBs on DFS (HR: 0.339, 95% CI: 0.135–0.850, p = 0.021) compared to ACEIs. Other factors affecting OS included age (HR: 1.044, 95% CI: 1.016–1.073, p = 0.002), regional lymph node metastasis (ypN +) (HR: 2.157, 95% CI: 1.395–3.334, p = 0.001) and perineural invasion (PNI) (HR: 3.864, 95% CI: 1.799–8.301, p = 0.001). Additional factors affecting DFS included ypN + (HR: 2.310, 95% CI: 1.374–3.883, p = 0.002) and PNI (HR: 4.351, 95% CI: 1.584–11.954, p = 0.004).ConclusionsThe use of ARBs instead of ACEIs may improve the outcome of the combined therapy for rectal cancer patients with associated hypertension.

683P Impact of renin-angiotensin system inhibitors (RASi) on outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICI)

RASi have been shown to improve outcomes in studies of multiple malignancies by effects on the tumor microenvironment to enhance the immune repertoire and improve drug delivery. We evaluated the impact of RASi on outcomes in mRCC patients receiving ICI.

Meta-analysis of impact of renin-angiotensin system inhibitors on survival after transcatheter aortic valve implantation.

To determine whether renin-angiotensin system inhibitor (RASI) prescription is associated with better survival after transcatheter aortic valve implantation (TAVI), we performed the first meta-analysis of currently available studies. To identify all studies reporting impact of RASI prescription on survival after TAVI, we searched PubMed, Web of Science, Google Scholar, etc. through October 2019. We extracted adjusted (if unavailable, unadjusted) hazard ratios (HRs) with their confidence intervals (CIs) of midterm (up to ≥6-month) all-cause mortality for RASI prescription from each study and combined study-specific estimates using inverse variance-weighted averages of logarithmic HRs in the random-effects model. We identified 13 eligible studies with a total of 26,132 TAVI patients and included them in the present meta-analysis. None was a randomized controlled trial, 5 were observational studies comparing patients with versus without RASI prescription (including 3 propensity score matched studies), and 8 were observational studies investigating RASI prescription as one of covariates. The primary meta-analysis of all studies demonstrated that RASI prescription was associated with significantly lower midterm mortality (HR=0.83; 95% CI: 0.76 to 0.92; P=0.0002). Although we identified significant funnel plot asymmetry (P=0.036 by the rank correlation test) suggesting publication bias, correcting for it using the trim-and-fill method did not substantially alter the result favoring RASI prescription (corrected HR=0.85; 95% CI: 0.76 to 0.95; P=0.004). RASI prescription may be associated with better midterm survival after TAVI.

Impact of renin-angiotensin system inhibitors after revascularization of patients with left main coronary artery disease.

There is a paucity of data regarding the effect of inhibition of the renin-angiotensin system on outcomes after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). We sought to examine long-term outcomes of patients with left main coronary disease (LMCAD) randomized to PCI with fluoropolymer-based cobalt-chromium everolimus-eluting stents or CABG according to treatment at discharge with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) in the large-scale, multicenter, randomized EXCEL trial. EXCEL randomized 1905 patients with LMCAD of low and intermediate anatomical complexity (visually-assessed SYNTAX score ≤32) to PCI (n = 948) versus CABG (n = 957). Patients were categorized according to whether they were treated with ACEI/ARB at discharge; their outcomes from discharge to 5 years were examined using multivariable logistic regression with an offset for follow-up time. Among 1775 patients discharged alive with known ACEI/ARB treatment status, 896 (50.5%) were treated with one of these agents. Among those treated with ACEI/ARB, the 5-year rate of all-cause death was similar after PCI or CABG (10.7% versus 9.8% respectively, adjOR, 0.94; 95% CI, 0.56-1.57) in contrast to patients not treated with ACEI/ARB (15.0% versus 7.8%, respectively, adjOR, 2.20; 95% CI, 1.32-3.67) (Pinteraction = 0.02). Significant interactions between treatment arm (PCI versus CABG) and ACEI/ARB treatment status were also found for cardiovascular death (Pinteraction = 0.03), ischemia-driven revascularization (Pinteraction = 0.03), target vessel revascularization (Pinteraction = 0.007) and target vessel failure (Pinteraction = 0.0009). In the EXCEL trial, the postdischarge rates of death and revascularization after 5 years were similar after PCI and CABG in patients with LMCAD treated with ACEI/ARB at discharge. In contrast, event rates were higher after PCI versus CABG in those not so treated.

Impact of renin-angiotensin system inhibitors and beta-blockers on dental implant stability

BackgroundCurrent experimental research suggests antihypertensive medication reduces the failure risk of dental implants due to enhanced bone remodeling. However, evidence from clinical studies evaluating the impact of antihypertensive medication on implant stability is lacking.MethodsWe retrospectively analyzed 377 implants in 196 patients (46 implants inserted in antihypertensive drug users (AH) and 331 implants in non-users (NAH)) for implant stability measured by radiofrequency analysis, and we determined the implant stability quotient (ISQ). AH subgroups were stratified by the use of beta-blockers, renin-angiotensin system (RAS) inhibitors, and both of the aforementioned. The impact of antihypertensive medication on ISQ values at implant insertion (primary stability) and implant exposure (secondary stability) was analyzed by a linear regression model with a regression coefficient and its 95% confidence interval (95% CI), adjusted for potential confounders.ResultsTime between implant insertion and implant exposure was 117.1 ± 56.6 days. ISQ values at insertion were 71.8 ± 8.7 for NAH and 74.1 ± 5.6 for AH, respectively. ISQ at exposure was 73.7 ± 8.1 for NAH and 75.7 ± 5.9 for AH. Regression analysis revealed that none of the AH subgroups were significantly related to ISQ at implant insertion. However, renin-angiotensin system inhibitors (RAS) were significantly associated with higher ISQ values at exposure (reg. coeff. 3.59, 95% CI 0.46–6.71 (p=0.025)).ConclusionsOutcome of the present study indicates enhanced bone remodeling and osseointegration following dental implant insertion in patients taking RAS inhibitors than in non-users. Future randomized prospective studies must confirm these indicative results.

Impact of renin-angiotensin system inhibitors on mortality during the COVID Pandemic among STEMI patients undergoing mechanical reperfusion: Insight from an international STEMI registry

BackgroundConcerns have been raised on a potential interaction between renin-angiotensin system inhibitors (RASI) and the susceptibility to coronavirus disease 2019 (COVID-19). No data have been so far reported on the prognostic impact of RASI in patients suffering from ST-elevation myocardial infarction (STEMI) during COVID-19 pandemic, which was the aim of the present study. MethodsSTEMI patients treated with primary percutaneous coronary intervention (PPCI) and enrolled in the ISACS-STEMI COVID-19 registry were included in the present sub-analysis and divided according to RASI therapy at admission. ResultsOur population is represented by 6095 patients, of whom 3654 admitted in 2019 and 2441 in 2020. No difference in the prevalence of SARSCoV2 infection was observed according to RASI therapy at admission (2.5% vs 2.1%, p = 0.5), which was associated with a significantly lower mortality (adjusted OR [95% CI]=0.68 [0.51–0.90], P = 0.006), confirmed in the analysis restricted to 2020 (adjusted OR [95% CI]=0.5[0.33–0.74], P = 0.001). Among the 5388 patients in whom data on in-hospital medication were available, in-hospital RASI therapy was associated with a significantly lower mortality (2.1% vs 16.7%, OR [95% CI]=0.11 [0.084–0.14], p < 0.0001), confirmed after adjustment in both periods. Among the 62 SARSCoV-2 positive patients, RASI therapy, both at admission or in-hospital, showed no prognostic effect. ConclusionsThis is the first study to investigate the impact of RASI therapy on the prognosis and SARSCoV2 infection of STEMI patients undergoing PPCI during the COVID-19 pandemic. Both pre-admission and in-hospital RASI were associated with lower mortality. Among SARSCoV2-positive patients, both chronic and in-hospital RASI therapy showed no impact on survival.

Outcomes of hospitalized patients with SARS-CoV-2 infection previously treated with renin-angiotensin system inhibitors

BackgroundRenin angiotensin system inhibitors (RASi) are largely prescribed in hypertensive patients. As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) penetrates respiratory epithelium through angiotensin converting enzyme 2 (ACE2) binding, the association between RASi and poorer outcomes has been questioned.PurposeThis study aimed to provide insight on the impact of RASi on SARS-CoV-2 outcomes in a population of patients hospitalized for COVID-19.MethodsThis is a retrospective analysis of consecutively hospitalized adult patients with SARS-CoV-2 infection (positive rtPCR) admitted to the University Hospital of Strasbourg from the 25th Feb, 2020 to the 1st Apr, 2020. Patients hospitalized for less than 24 h were excluded and the observation period ended at hospital discharge.ResultsDuring the study period, 943 COVID-19 patients were hospitalized in our institution, of whom 772 were included in this analysis. Among them, 431 patients had previously known hypertension. The median age was 68 (56–79). The cohort was divided into two subgroups based on RASi treatment on admission: “RASi” (n = 282) and “RASi-free” (n = 490). Both groups had similar clinical presentations and equivalent recourse to endotracheal intubation, high flow nasal oxygen (HFNO) or non-invasive ventilation (NIV). Overall, 220 patients were placed under mechanical ventilation of whom 30% died. Severe pneumonia (defined as either leading to death, and/or requiring intubation, HFNO, NIV and/or requiring an oxygen rate flow ≥ 5l/min) and death occurred more frequently in RASi treated patients (63% vs. 53% and respectively 27.3% versus 18.2%). In a multivariate logistic-regression model, neither severe pneumonia nor death were associated with RASi treatment.ConclusionOur study showed no correlation between RASi treatment and death or severe COVID-19 pneumonia.

Outcomes of COVID-19 Hospitalized Patients Previously Treated with Renin-Angiotensin System Inhibitors.

(1) Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) penetrates respiratory epithelium through angiotensin-converting enzyme-2 binding, raising concerns about the potentially harmful effects of renin–angiotensin system inhibitors (RASi) on Human Coronavirus Disease 2019 (COVID-19) evolution. This study aimed to provide insight into the impact of RASi on SARS-CoV-2 outcomes in patients hospitalized for COVID-19. (2) Methods: This was a retrospective analysis of hospitalized adult patients with SARS-CoV-2 infection admitted to a university hospital in France. The observation period ended at hospital discharge. (3) Results: During the study period, 943 COVID-19 patients were admitted to our institution, of whom 772 were included in this analysis. Among them, 431 (55.8%) had previously known hypertension. The median age was 68 (56–79) years. Overall, 220 (28.5%) patients were placed under mechanical ventilation and 173 (22.4%) died. According to previous exposure to RASi, we defined two groups, namely, “RASi” (n = 282) and “RASi-free” (n = 490). Severe pneumonia (defined as leading to death and/or requiring intubation, high-flow nasal oxygen, noninvasive ventilation, and/or oxygen flow at a rate of ≥5 L/min) and death occurred more frequently in RASi-treated patients (64% versus 53% and 29% versus 19%, respectively). However, in a propensity score-matched cohort derived from the overall population, neither death (hazard ratio (HR) 0.93 (95% confidence interval (CI) 0.57–1.50), p = 0.76) nor severe pneumonia (HR 1.03 (95%CI 0.73–1.44), p = 0.85) were associated with RASi therapy. (4) Conclusion: Our study showed no correlation between previous RASi treatment and death or severe COVID-19 pneumonia after adjustment for confounders.

Impact of renin-angiotensin system inhibitors on outcomes after surgical or transcatheter aortic valve replacement. A meta-analysis

Introduction and objectivesTo determine whether renin-angiotensin system inhibitor (RASi) prescription is associated with better outcomes after transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR). MethodsAll comparative studies of RASi vs no RASi prescription in patients undergoing TAVI/SAVR were gathered from PubMed, Web of Science, and Google Scholar through August, 2019. We extracted hazard ratios (HRs) with their confidence intervals (CIs) for mortality from each study and combined study-specific estimates using inverse variance-weighted averages of logarithmic HRs in the random effects model. ResultsWe identified 6 eligible studies with a total of 21 390 patients (TAVI: 17 846; SAVR: 3544) and included them in the present meta-analysis. The 6 studies were observational comparative studies (including 3 propensity score matched and 3 cohort studies) of RASi vs no RASi prescription. The analysis demonstrated that RASi prescription was associated with significantly lower mortality in the whole group of patients undergoing aortic valve intervention (HR, 0.64; 95%CI, 0.47-0.88; P <.001). However, subgroup analysis suggested differences according to the selected therapy, with TAVI showing better mortality rates in the RASi group (HR, 0.67; 95%CI, 0.49-0.93) but not in the SAVR group (HR, 0.61; 95%CI, 0.29-1.30). No funnel plot asymmetry was identified, suggesting minimum publication bias. Sensitivity analyses sequentially eliminating dissimilar studies did not substantially alter the primary result favoring RASI prescription. ConclusionsThese findings suggest a mortality benefit of RASi in patients with AS treated with aortic valve replacement that might be particularly relevant following TAVI. Future randomized studies are warranted to confirm this relevant finding.

Impact of renin-angiotensin system inhibitors on outcomes after transcatheter aortic valve replacement: A meta-analysis.

We aimed to evaluate the impact of renin-angiotensin system (RAS) inhibitors on outcomes after transcatheter aortic valve replacement (TAVR). The impact of RAS inhibitors on outcomes after TAVR was unclear. A systematic review of articles comparing outcomes of patients using and not using RAS inhibitors after TAVR was performed through PubMed, Embase, and Cochrane. Primary outcome was midterm all-cause mortality. Risk ratios (RRs) were calculated with the corresponding 95% confidence interval using random effect models. Five studies with 23,319 patients were included. Patients treated with RAS inhibitors had lower midterm all-cause mortality after TAVR than those without RAS inhibitors in both the unmatched (13.3 vs. 17.2%, RR 0.77, p = .005) and propensity score matched cohorts (13.5 vs 16.2%, RR 0.83, p < .001). Cardiovascular mortality (10.4 vs. 15.6%, RR 0.68, p < .001), rate of heart failure readmission (12.2 vs. 14.5%, RR 0.80, p = .006), and new-onset atrial fibrillation (14.0 vs. 23.7%, RR 0.73, p = .003) were also lower with RAS inhibitors. No difference was found between two groups regarding cerebrovascular events, myocardial infarction, major bleeding, major vascular complications, acute kidney injury, permanent pacemaker implantation, and moderate/severe paravalvular aortic regurgitation. RAS inhibitors were associated with lower midterm all-cause mortality after TAVR.

Association of renin-angiotensin system inhibitors with long-term outcomes in patients with systolic heart failure and moderate-to-severe kidney function impairment

PurposeAlthough guidelines recommend that patients with heart failure with reduced ejection fraction (HFrEF) should be treated with renin-angiotensin system (RAS) inhibitors, the long-term efficacy of RAS inhibitors in HFrEF patients with moderate-to-severe chronic kidney disease (CKD) remains unclear. MethodsThe present study included consecutive patients hospitalized for acute heart failure across five Japanese teaching hospitals. The impact of RAS inhibitors on 2-year all-cause mortality was evaluated in patients with an ejection fraction ≤40% and CKD, defined as an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2, at discharge. Its severity was subclassified from 3B to 5 according to eGFR. ResultsOverall, 553 patients (age, 76 ± 11 years; 68% male) were included. RAS inhibitors were prescribed more frequently in 227 patients with stage 3B (71.2%) than in 107 patients with stage 4 or 5 CKD (45.7%). All-cause mortality was recorded in 119 patients (23.4%) (55 [18.5%] patients with stage 3B; 64 [30.3%] patients with stage 4 or 5 CKD), within the median follow-up period of 609 (220–983) days. After many-to-one propensity score matching (87 pairs in stage 3; 60 pairs in stage 4 or 5 CKD), those with RAS inhibitors had reduced mortality rate in stage 3B (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.19–0.83) but not in stage 4 or 5 CKD (HR, 1.08; 95% CI, 0.57–2.03). ConclusionsIn HFrEF patients with CKD, RAS inhibitors are associated with reduction in mortality in stage 3B CKD, but the association is less clear in stage 4 or 5 CKD.