renin-angiotensin system inhibitors

肾素 - 血管紧张素系统抑制剂
  • 文章类型: Journal Article
    围手术期心肌损伤影响经导管主动脉瓣置换术(TAVR)后的临床结果。尚未建立与TAVR相关的围手术期心肌损伤的最佳医疗管理策略。
    作者旨在研究肾素-血管紧张素系统(RAS)抑制剂在TAVR术后围手术期心肌损伤患者中的预后相关性。
    在未来的TAVR注册中,根据TAVR后瓣膜学术研究联盟(VARC)-3围手术期心肌损伤和RAS抑制剂处方对患者进行回顾性分层.感兴趣的主要结果是心肌损伤和心血管死亡的患病率。使用Logistic和Cox比例风险回归分析感兴趣的结果。
    在2007年8月至2023年6月期间接受TAVR的2,083例合格患者中,有283例(13.8%)发生了VARC-3围手术期心肌损伤。197例(70%)围手术期心肌损伤患者和1,251例(71.2%)无损伤患者使用RAS抑制剂。与无围手术期心肌损伤的患者相比,心肌损伤患者1年时心血管死亡风险增加(HR校正:2.08;95%CI:1.39~3.11).TAVR后使用RAS抑制剂与有和没有围手术期心肌损伤的患者心血管死亡风险降低相关(HRadjusted:0.46;95%CI:0.22-0.95,HRadjusted:0.44;95%CI:0.30-0.65)。
    7例接受TAVR的患者中有1例出现围手术期心肌损伤。VARC-3围手术期心肌损伤与TAVR后1年心血管死亡风险增加2倍相关。RAS抑制剂处方的有利关联在有和没有围手术期心肌损伤的患者中是一致的。(瑞士TAVI注册;NCT01368250)。
    UNASSIGNED: Periprocedural myocardial injury impacts clinical outcome after transcatheter aortic valve replacement (TAVR). The optimal medical management strategy for TAVR-related periprocedural myocardial injury has not been established.
    UNASSIGNED: The authors aimed to investigate the prognostic association of renin-angiotensin system (RAS) inhibitors in patients with periprocedural myocardial injury after TAVR.
    UNASSIGNED: In a prospective TAVR registry, patients were retrospectively stratified according to Valve Academic Research Consortium (VARC)-3 periprocedural myocardial injury and RAS inhibitor prescription after TAVR. The main outcomes of interest were prevalence of myocardial injury and cardiovascular death. Logistic and Cox proportional hazards regression were used to analyze outcomes of interest.
    UNASSIGNED: Among 2,083 eligible patients undergoing TAVR between August 2007 and June 2023, 283 patients (13.8%) developed VARC-3 periprocedural myocardial injury. RAS inhibitors were prescribed in 197 patients (70%) with periprocedural myocardial injury and in 1,251 patients (71.2%) without injury. Compared with patients without periprocedural myocardial injury, patients with myocardial injury had an increased risk of cardiovascular death at 1 year (HRadjusted: 2.08; 95% CI: 1.39-3.11). The use of RAS inhibitors after TAVR was associated with a reduced risk of cardiovascular death in patients with and without periprocedural myocardial injury (HRadjusted: 0.46; 95% CI: 0.22-0.95, and HRadjusted: 0.44; 95% CI: 0.30-0.65, respectively).
    UNASSIGNED: One out of 7 patients undergoing TAVR experienced periprocedural myocardial injury. VARC-3 periprocedural myocardial injury was associated with a 2-fold increased risk of cardiovascular death at 1 year after TAVR. The favorable association of RAS inhibitor prescription was consistent in patients with and without periprocedural myocardial injury. (SwissTAVI Registry; NCT01368250).
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  • 文章类型: Journal Article
    UNASSIGNED: Hospital admission for a critical illness episode creates communication breakpoints and can lead to medication discrepancies during hospital stays. Due to the patient\'s underlying condition and the care setting, chronic medications such as cardiovascular medication are often held, discontinued, or changed to alternative administration routes. Unfortunately, data on the optimal timing of cardiovascular drug reinitiation among intensive care unit (ICU) survivors are lacking.
    UNASSIGNED: The primary objective of this study was to describe the prevalence of chronic cardiovascular medication taken before hospital admission and discontinued at ICU discharge and hospital discharge for critically ill patients. A secondary objective was to assess factors associated with medication discontinuation.
    UNASSIGNED: We conducted a multicentered retrospective cohort study at 2 tertiary academic hospitals in Canada. All adult patients taking cardiovascular medication before ICU admission and surviving to hospital discharge between April 1, 2016, and April 1, 2017, were eligible.
    UNASSIGNED: The main outcome of the study was the discontinuation of cardiovascular medication prescribed before ICU admission. The outcome was assessed through participants\' chart review.
    UNASSIGNED: We included 352 patients with a median age of 71.0 years. A total of 155 patients (44.03%) had at least 1 cardiovascular medication discontinued during their stay. Our adjusted model uncovered 3 factors associated with cardiovascular medication discontinuation: male sex (odds ratio [OR] = 0.564, 95% confidence interval [CI] = 0.346-0.919), number of cardiovascular medications taken preadmission (OR = 1.669, 95% CI = 1.003-2.777 for 2 medications and OR = 3.170, 95% CI = 1.325-7.583), and the use of vasopressors (OR = 1.770, 95% CI = 1.045-2.997).
    UNASSIGNED: Our study uncovered that cardiovascular medication discontinuation for ICU patients is frequent, especially for renin-angiotensin system (RAS) blockers. Data from our study could be used to reinforce site-specific protocols of medication reconciliation and optimization, as well as inform future protocols aimed at RAS blocker reinitiation follow-up.
    UNASSIGNED: L’admission à l’hôpital pour un épisode de maladie grave crée des ruptures de communication et peut entraîner des écarts dans la médication pendant le séjour à l’hôpital. Il arrive souvent, selon l’état sous-jacent du patient et l’environnement de soins, que les médicaments destinés à traiter des maladies chroniques, comme les médicaments cardiovasculaires, soient poursuivis, cessés ou administrés par d’autres voies. On manque malheureusement de données sur le moment optimal pour la reprise du traitement cardiovasculaire chez les survivants des unités de soins intensifs (USI).
    UNASSIGNED: L’objectif principal était de décrire la prévalence de l’arrêt, à la sortie de l’USI et de l’hôpital, des médicaments pris par les patients gravement malades pour traiter les maladies cardiovasculaires chroniques avant leur admission. Un objectif secondaire était d’évaluer les facteurs associés à l’arrêt du traitement.
    UNASSIGNED: Nous avons mené une étude de cohorte rétrospective multicentrique dans deux hôpitaux universitaires tertiaires canadiens. Étaient admissibles tous les patients adultes qui prenaient des médicaments cardiovasculaires avant leur admission à l’USI entre le 1er avril 2016 et le 1er avril 2017 et qui avaient survécu jusqu’à leur sortie de l’hôpital.
    UNASSIGNED: Le principal critère d’intérêt était l’arrêt du traitement cardiovasculaire prescrit avant l’admission à l’USI. Ce critère a été établi par l’examen des dossiers des sujets.
    UNASSIGNED: Nous avons inclus 352 patients (âge médian : 71,0 ans) desquels 155 (44 %) avaient vu au moins un de leurs médicaments pour traiter une maladie cardiovasculaire cessé pendant leur séjour. Notre modèle corrigé a révélé trois facteurs associés à l’arrêt du traitement cardiovasculaire : être de sexe masculin (rapport de cotes [RC] : 0,564; IC95 % : 0,346-0,919), le nombre de médicaments cardiovasculaires pris avant l’admission (RC : 1,669; IC95 % : 1,003-2,777 pour deux médicaments, et RC : 3,170; IC95 % : 1,325-7,583) et l’utilisation de vasopresseurs (RC : 1,770; IC95 % : 1,045-2,997).
    UNASSIGNED: Notre étude a révélé que l’arrêt du traitement contre les maladies cardiovasculaires chroniques, en particulier les inhibiteurs du SRA, est fréquent chez les patients hospitalisés aux soins intensifs. Les données de notre étude pourraient servir à renforcer les protocoles de bilan de médication et d’optimisation propre à chaque site de même que pour éclairer les futurs protocoles visant à assurer le suivi de la réinitiation des inhibiteurs du SRA.
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  • 文章类型: Journal Article
    背景:经导管主动脉瓣置换术(TAVR)后的最佳医学治疗策略尚未建立,并且可能受到瓣膜外心脏损伤程度的影响。我们旨在研究肾素-血管紧张素系统(RAS)抑制剂对TAVR患者的预后作用,该作用是根据瓣膜外心脏损害的程度进行分层的。
    方法:在前瞻性TAVR注册中,我们对患者的基线心脏损害进行了回顾性评估,并根据既定标准将患者分为5个阶段(0~4).根据出院时的RAS抑制剂处方比较1年的临床结果。
    结果:在2007年8月至2021年6月期间接受TAVR的2,247名符合条件的患者中,有1,634名(72.7%)在出院时服用了RAS抑制剂。83例患者(3.7%)分为0期,276例(12.3%)分为1期,889例(39.6%)分为2期,489例(21.8%)分为3期,510例(22.7%)分为4期。TAVR后RAS抑制剂处方与1年死亡率风险降低相关(HRadjusted0.59,95%CI0.45-0.77)。心脏3期和4期患者的保护作用更加明显(分别为HR调整0.54,95%CI0.32-0.92和HR调整0.58,95%CI0.36-0.92),但在第2阶段无统计学意义(HR校正0.70,95%CI0.43-1.14)。
    结论:在接受TAVR的患者中,我们发现RAS抑制剂处方与整体人群的临床结局改善密切相关,并且在心脏损伤的各个阶段都没有异质性的迹象。
    BACKGROUND: The optimal medical treatment strategy after transcatheter aortic valve replacement (TAVR) has not been established, and might be affected by the extent of extravalvular cardiac damage. We aimed to investigate the prognostic association of renin-angiotensin system (RAS) inhibitors in TAVR patients stratified according to the extent of extravalvular cardiac damage.
    METHODS: In a prospective TAVR registry, patients were retrospectively evaluated for baseline cardiac damage and classified into 5 stages of cardiac damage (0-4) according to established criteria. Clinical outcomes at 1 year were compared according to RAS inhibitor prescription at discharge.
    RESULTS: Among 2247 eligible patients who underwent TAVR between August 2007 and June 2021, 1634 (72.7%) were prescribed RAS inhibitors at discharge. Eighty-three patients (3.7%) were classified as stage 0, 276 (12.3%) as stage 1, 889 (39.6%) as stage 2, 489 (21.8%) as stage 3, and 510 (22.7%) as stage 4. RAS inhibitor prescription after TAVR was associated with a reduced risk of 1-year mortality (adjusted hazard ratio [HRadjusted], 0.59; 95% confidence interval [CI], 0.45-0.77). The protective association was accentuated among patients with cardiac stages 3 and 4 (HRadjusted, 0.54 [95% CI, 0.32-0.92]; and HRadjusted, 0.58 [95% CI, 0.36-0.92], respectively), but not statistically significant in for those with stage 2 (HRadjusted, 0.70; 95% CI, 0.43-1.14).
    CONCLUSIONS: In patients who underwent TAVR, we found a strong association of RAS inhibitor prescription and improved clinical outcome in the overall population, and there were no signs of heterogeneity across stages of cardiac damage.
    BACKGROUND: NCT01368250.
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  • 文章类型: Journal Article
    缺乏关于二甲双胍和肾素-血管紧张素系统抑制剂(RASis)对钠-葡萄糖协同转运蛋白-2抑制剂(SGLT2i)相关肾脏结局的影响的真实世界证据。本研究旨在调查2型糖尿病患者合并使用二甲双胍或RAS是否改变SGLT2i相关肾脏结局。
    SGLT2i用户在2016年5月和2017年12月期间从三个电子健康记录数据库中被识别,并被分为有和没有同时使用二甲双胍或RASis的用户。进行倾向评分匹配以最小化组间的基线差异。研究结果是平均估计的肾小球滤过率(eGFR)变化和时间达到30%,40%,和50%的eGFR降低。进行了荟萃分析,以结合数据库中的估计值。
    匹配后,有6,625和3,260名SGLT2i用户有和没有二甲双胍,以及6,654和2,746个SGLT2i用户,分别。有和没有二甲双胍治疗的SGLT2i用户的eGFR下降相似,但与没有RAS的用户相比,使用RAS的SGLT2i用户更大。二甲双胍和RASi的使用对SGLT2i相关的eGFR降低均无显著影响,如使用二甲双胍/RASis的SGLT2is降低30%eGFR的危险比(95%CI)所证明的那样,即1.02(0.87-1.20)/1.09(0.92-1.31)。在eGFR降低40%和50%的结果中也观察到了这些发现。
    使用二甲双胍或RASis并未改变2型糖尿病患者SGLT2i相关肾脏结局。
    UNASSIGNED: There is a lack of real-world evidence regarding the impact of concomitant metformin and renin-angiotensin system inhibitors (RASis) on sodium-glucose cotransporter-2 inhibitor (SGLT2i)-associated kidney outcomes. This study was aimed to investigate whether SGLT2i-associated kidney outcomes were modified by the concomitant use of metformin or RASis in patients with type 2 diabetes.
    UNASSIGNED: SGLT2i users were identified from three electronic health record databases during May 2016 and December 2017 and categorized into those with and without concomitant use of metformin or RASis. Propensity score matching was performed to minimize baseline differences between groups. Study outcomes were mean estimated glomerular filtration rate (eGFR) change and time to 30%, 40%, and 50% eGFR reductions. A meta-analysis was performed to combine the estimates across databases.
    UNASSIGNED: After matching, there were 6,625 and 3,260 SGLT2i users with and without metformin, and 6,654 and 2,746 SGLT2i users with and without RASis, respectively. The eGFR dip was similar in SGLT2i users with and without metformin therapy, but was greater in SGLT2i users with RASis compared to those without RASis. Neither metformin nor RASi use had a significant effect on SGLT2i-associated eGFR reductions, as evidenced by the hazard ratios (95% CIs) of 30% eGFR reductions for SGLT2is with versus without metformin/RASis, namely 1.02 (0.87-1.20)/1.09 (0.92-1.31). Such findings were also observed in the outcomes of 40% and 50% eGFR reductions.
    UNASSIGNED: Using metformin or RASis did not modify SGLT2i-associated kidney outcomes in type 2 diabetes.
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  • 文章类型: Journal Article
    背景:许多指南都推荐肾素-血管紧张素系统抑制剂(RASI)作为慢性肾脏病(CKD)患者的一线治疗方法。我们研究了2010年至2019年RASI处方趋势,并分析了中国住院CKD患者与RASI处方相关的特征。
    目的:研究肾素血管紧张素系统抑制剂在中国CKD住院患者中的处方。
    方法:回顾性分析,横断面回顾2010年至2019年中国住院CKD患者的RASI处方。分析了2010年至2019年的RASI处方趋势,并进行了双变量和多变量逻辑回归分析,以确定与RASI处方相关的特征。
    结果:共纳入35090例CKD患者,10043(28.6%)RASI处方。在这些患者中,18919(53.9%)符合基于2012肾脏疾病:改善全球结果指南的RASI治疗标准。其中,7246例(38.3%)患者接受RASI处方。RASI处方从2011年到2012年显示出最初的快速增长,在2015年和2016年左右达到峰值,然后表现出随后的小幅下降趋势。双变量和多变量分析都表明,包括男性,年龄小于60岁,肾内科入院,CKD阶段较低,高血压或糖尿病史,蛋白尿,肾小球肾炎作为CKD的病因,非急性肾损伤与RASI处方相关。
    结论:近年来,RASI处方的使用频率呈初期增加趋势,但略有下降。CKD患者具有某些特征,如高龄,晚期疾病阶段,外科入院,或急性肾损伤患者接受RASI处方的可能性较小.RASI在住院CKD患者中的应用不足。实际临床实践有待改进。相关研究的开展有助于指导临床治疗策略的正确选择。
    BACKGROUND: Many guidelines have recommended renin-angiotensin system inhibitors (RASI) as the first-line treatment for patients with chronic kidney disease (CKD). We studied RASI prescription trends from 2010 to 2019, and analyzed the characteristics associated with RASI prescription in Chinese hospitalized CKD patients.
    OBJECTIVE: To study the prescription of renin angiotensin system inhibitors in hospitalized patients with CKD in China.
    METHODS: It was retrospectively, cross-sectional reviewed RASI prescriptions in hospitalized CKD patients in China from 2010 to 2019. RASI prescribing trends were analyzed from 2010 to 2019, and bivariate and multivariate logistic regression analyses were conducted to identify characteristics associated with RASI prescription.
    RESULTS: A total of 35090 CKD patients were included, with 10043 (28.6%) RASI prescriptions. Among these patients, 18919 (53.9%) met the criteria for RASI treatments based on the 2012 kidney disease: Improving global outcomes guidelines. Of these, 7246 (38.3%) patients received RASI prescriptions. RASI prescriptions showed an initial rapid increase from 2011 to 2012, reached its peak around 2015 and 2016, and then exhibited a subsequent slight decreasing trend. Both bivariate and multivariate analyses showed that several characteristics, including the male gender, age less than 60-year-old, nephrology department admission, lower CKD stage, history of hypertension or diabetes, proteinuria, glomerulonephritis as the CKD etiology, and non-acute kidney injury were associated with RASI prescriptions.
    CONCLUSIONS: The frequency of RASI prescriptions showed an initial increase but a slight decreasing trend in more recent years. CKD patients with certain characteristics such as elderly age, advanced disease stage, surgery department admission, or acute kidney injury were less likely to receive RASI prescriptions. In the application of RASI in hospitalized CKD patients is insufficient. The actual clinical practice needs to be improved. The development of related research is helpful to guide the correct choice of clinical treatment strategy.
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  • 文章类型: Journal Article
    肾素-血管紧张素系统抑制剂(RASI)对接受免疫检查点抑制剂(ICIs)治疗的高血压癌症患者的预后的影响仍然不明确。本研究旨在阐明在ICIs治疗的背景下使用RASI对该特定患者组的预后的影响。渴望为理性提供更清晰的基础,这些药物的临床处方中的循证选择。
    在PubMed上进行了全面搜索,Embase,WebofScience,和Cochrane图书馆的原始研究发表到2023年8月6日。包括以英文报道的总生存期(OS)和/或无进展生存期(PFS)的95%置信区间(CI)的风险比(HR)发表的研究。使用R软件(版本4.2.2)执行所有统计分析。
    共13项研究,包括大约12,595名患者,满足纳入标准。荟萃分析表明,RASI的使用与OS中的有利结果之间存在统计学上的显着关联(HR,0.74;95%CI,0.62-0.88)和PFS(HR,0.77;95%CI,0.62-0.96)在接受ICIs治疗的癌症患者中。
    这项研究提供了令人信服的证据,支持RASI对接受ICI的癌症患者的有益预后影响。RASI为接受ICIs治疗的高血压癌症患者提供了一种可行的抗高血压药物选择。通过前瞻性研究进一步探索和验证是必要的,以建立使用RASIs管理接受ICIs免疫治疗的高血压癌症患者的明确指南。
    https://www.crd.约克。AC.英国/普华永道/,标识符CRD42023454886。
    UNASSIGNED: 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.
    UNASSIGNED: 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).
    UNASSIGNED: 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.
    UNASSIGNED: 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.
    UNASSIGNED: https://www.crd.york.ac.uk/prospero/, identifier CRD42023454886.
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  • 文章类型: Journal Article
    背景:肾素-血管紧张素系统抑制剂(RASi)治疗是IgA肾病(IgAN)患者的基础治疗。然而,很少有生物标志物可以预测RASi的疗效。本研究旨在寻找与RASi治疗IgAN患者蛋白尿疗效相关的尿外泌体mRNA。
    方法:我们将筛查队列中的IgAN患者分为A1(3个月时蛋白尿增加),B1(3个月时蛋白尿减少小于50%),C1(3个月时蛋白尿下降50%以上)组治疗后根据蛋白尿的变化。活检前收集尿液外泌体,提取RNA并用微阵列测定进行分析。通过差异表达基因(DEGs)分析筛选候选基因,然后在验证队列中通过定量实时聚合酶链反应(qPCR)进行验证。使用受试者工作特征(ROC)曲线评估基因性能,以预测RASi减少IgAN患者蛋白尿的治疗效果。
    结果:ECE1和PDE1AmRNA在三组间有显著差异,A1、B1、C1组逐渐降低。在验证队列中,与C2组相比,A2组的尿外泌体ECE1和PDE1AmRNA水平也显着降低(ECE1,P<0.001;PDE1A,P<0.01)。此外,B2组ECE1mRNA水平也低于C2组(P<0.01)。ROC曲线验证了尿外泌体ECE1和PDE1A基因水平预测IgAN患者的RASi疗效,曲线下面积(AUC)分别为0.68和0.63。
    结论:尿外泌体ECE1和PDE1AmRNA的表达可作为潜在的生物标志物,用于预测RASi疗效以减少IgAN患者的蛋白尿。
    BACKGROUND: Renin-angiotensin system inhibitors (RASi) treatment is the basic therapy for IgA nephropathy (IgAN) patients. However, there is few of biomarker that can predict the efficacy of RASi. This study aimed to find urinary exosomal mRNAs related to the therapeutic effect of RASi in the treatment of proteinuria in IgAN patients.
    METHODS: We divided IgAN patients in screening cohort into A1 (proteinuria increase at 3 months), B1 (proteinuria decrease less than 50 % at 3 months), C1 (proteinuria decrease more than 50 % at 3 months) groups according to changes of proteinuria after treatment. The urinary exosomes were collected before biopsy, RNAs were extracted and analyzed with the microarray assay. The candidate genes were screened by differentially expressed genes (DEGs) analysis and then validated by quantitative real-time polymerase chain reaction (qPCR) in a validation cohort. A receiver operating characteristic (ROC) curve was used to evaluate gene performance in predicting therapeutic effect on RASi reducing proteinuria in IgAN patients.
    RESULTS: ECE1 and PDE1A mRNAs were significantly different among the three groups, and were gradually decreased among A1, B1 and C1 groups. In the validation cohort, the level of urinary exosomal ECE1 and PDE1A mRNAs were also significantly lower in A2 group compared with C2 group(ECE1, P < 0.001;PDE1A, P < 0.01). Besides, the level of ECE1 mRNA was also lower in B2 group compared with C2 group (P < 0.01). The ROC curve verified that urinary exosomal ECE1 and PDE1A gene level predicted RASi efficacy in IgAN patients with area under curve (AUC) 0.68 and 0.63 respectively.
    CONCLUSIONS: Urinary exosomal ECE1 and PDE1A mRNAs expression can serve as potential biomarkers for predicting the RASi efficacy to reduce proteinuria in IgAN patients.
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  • 文章类型: Journal Article
    对于晚期慢性肾脏病(CKD)患者是否应停用肾素-血管紧张素系统抑制剂(RASI)存在争议。最近,据报道,晚期CKD患者停止RASI与死亡率和心血管事件(CV)增加相关;尚不清楚在透析开始前停止RASI是否会影响透析后的临床结局,这项研究旨在评估。在日本的这项多中心前瞻性队列研究中,我们纳入了717名患者(平均年龄,67岁;68%的男性)肾病护理持续时间≥90天,开始血液透析,并在血液透析开始前3个月使用RASI。多变量校正Cox模型用于比较650(91%)在血液透析开始之前持续RASI的患者和67(9.3%)停止RASI的患者之间的死亡率和CV事件风险。在3.5年的中位随访期间,170例(24%)患者死亡,228例(32%)发生CV事件。与连续RASI相比,终止RASI与死亡率无关(校正风险比[aHR]:0.82;95%置信区间[CI]:0.50-1.34),但与较高的CV事件相关(aHR:1.59;95%CI:1.06-2.38).亚组分析显示,在年龄<75岁的患者中,因CV事件停止RASI的风险特别高。停止RASI和年龄之间存在显著的相互作用。这项研究表明,在透析开始前立即停止RASI的患者与随后的较高CV事件有关。主动筛查CV疾病可能对这些患者特别有益。
    It is controversial whether renin-angiotensin system inhibitors (RASIs) should be stopped in patients with advanced chronic kidney disease (CKD). Recently, it was reported that stopping RASIs in advanced CKD was associated with increased mortality and cardiovascular (CV) events; however, it remains unclear whether stopping RASIs before dialysis initiation affects clinical outcomes after dialysis, which this study aimed to evaluate. In this multicenter prospective cohort study in Japan, we included 717 patients (mean age, 67 years; 68% male) who had a nephrology care duration ≥90 days, initiated hemodialysis, and used RASIs 3 months before hemodialysis initiation. The multivariable adjusted Cox models were used to compare mortality and CV event risk between 650 (91%) patients who continued RASIs until hemodialysis initiation and 67 (9.3%) patients who stopped RASIs. During a median follow-up period of 3.5 years, 170 (24%) patients died and 228 (32%) experienced CV events. Compared with continuing RASIs, stopping RASIs was unassociated with mortality (adjusted hazard ratio [aHR]: 0.82; 95% confidence interval [CI]: 0.50-1.34) but was associated with higher CV events (aHR: 1.59; 95% CI: 1.06-2.38). Subgroup analyses showed that the risk of stopping RASIs for CV events was particularly high in patients aged <75 years, with a significant interaction between stopping RASIs and age. This study revealed that patients who stopped RASIs immediately before dialysis initiation were associated with subsequent higher CV events. Active screening for CV disease may be especially beneficial for these patients.
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  • 文章类型: Randomized Controlled Trial
    背景:术前血浆N末端B型利钠肽(NT-proBNP>100pgml-1)升高的患者在非心脏手术后会出现更多并发症。使用肾素-血管紧张素系统(RAS)抑制剂治疗心脏代谢疾病的个体特别容易发生围手术期心肌损伤和并发症。我们假设在手术前停用RAS抑制剂会增加围手术期心肌损伤的风险,根据血浆NT-proBNP浓度的术前风险分层。
    方法:在对英国六个中心的2a期试验的预先计划分析中,≥60岁的择期非心脏手术患者在手术前被随机分配停止或继续使用RAS抑制剂.单个RAS抑制剂的药代动力学特征确定了手术前停用的时间。主要结果,给调查人员蒙面,临床医生,和病人,是心肌损伤(血浆高敏肌钙蛋白T≥15ngL-1或≥5ngL-1增加,术前高敏肌钙蛋白-T≥15ngL-1),术后48h内。感兴趣的共同暴露为术前血浆NT-proBNP(<或>100μgml-1)和停止或继续RAS抑制剂。
    结果:在241名参与者中,101(41.9%;平均年龄71[7]岁;48%女性)术前NT-proBNP>100pgml-1(中位数339[160-833]pgml-1),其中9/101(8.9%)被正式诊断为心力衰竭。63/101(62.4%)NT-proBNP>100pgml-1的受试者发生心肌损伤,而45/140(32.1%)NT-proBNP<100pgml-1的受试者发生心肌损伤。对于术前NT-proBNP<100pgml-1的受试者,停用RAS抑制剂的30/75(40%)有心肌损伤,与继续使用RAS抑制剂的15/65(23.1%)相比(停用OR为2.22[95%CI1.06-4.65];P=0.03)。对于术前NT-proBNP>100pgml-1,无论停止(62.2%)还是继续(62.5%)RAS抑制剂(或停止0.98[95%CI0.44-2.22]),心肌损伤率相似。
    结论:在低风险患者中停用肾素-血管紧张素系统抑制剂(术前NT-proBNP<100pgml-1)会增加非心脏手术前心肌损伤的可能性。
    BACKGROUND: Patients with elevated preoperative plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP >100 pg ml-1) experience more complications after noncardiac surgery. Individuals prescribed renin-angiotensin system (RAS) inhibitors for cardiometabolic disease are at particular risk of perioperative myocardial injury and complications. We hypothesised that stopping RAS inhibitors before surgery increases the risk of perioperative myocardial injury, depending on preoperative risk stratified by plasma NT-proBNP concentrations.
    METHODS: In a preplanned analysis of a phase 2a trial in six UK centres, patients ≥60 yr old undergoing elective noncardiac surgery were randomly assigned either to stop or continue RAS inhibitors before surgery. The pharmacokinetic profile of individual RAS inhibitors determined for how long they were stopped before surgery. The primary outcome, masked to investigators, clinicians, and patients, was myocardial injury (plasma high-sensitivity troponin-T ≥15 ng L-1 or a ≥5 ng L-1 increase, when preoperative high-sensitivity troponin-T ≥15 ng L-1) within 48 h after surgery. The co-exposures of interest were preoperative plasma NT-proBNP (< or >100 pg ml -1) and stopping or continuing RAS inhibitors.
    RESULTS: Of 241 participants, 101 (41.9%; mean age 71 [7] yr; 48% females) had preoperative NT-proBNP >100 pg ml -1 (median 339 [160-833] pg ml-1), of whom 9/101 (8.9%) had a formal diagnosis of cardiac failure. Myocardial injury occurred in 63/101 (62.4%) subjects with NT-proBNP >100 pg ml-1, compared with 45/140 (32.1%) subjects with NT-proBNP <100 pg ml -1 {odds ratio (OR) 3.50 (95% confidence interval [CI] 2.05-5.99); P<0.0001}. For subjects with preoperative NT-proBNP <100 pg ml-1, 30/75 (40%) who stopped RAS inhibitors had myocardial injury, compared with 15/65 (23.1%) who continued RAS inhibitors (OR for stopping 2.22 [95% CI 1.06-4.65]; P=0.03). For preoperative NT-proBNP >100 pg ml-1, myocardial injury rates were similar regardless of stopping (62.2%) or continuing (62.5%) RAS inhibitors (OR for stopping 0.98 [95% CI 0.44-2.22]).
    CONCLUSIONS: Stopping renin-angiotensin system inhibitors in lower-risk patients (preoperative NT-proBNP <100 pg ml -1) increased the likelihood of myocardial injury before noncardiac surgery.
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  • 文章类型: Journal Article
    背景:肾素-血管紧张素系统抑制剂(RASi)在老年高血压和有骨折风险的患者中的治疗效果一直备受关注,因为越来越多的证据表明骨组织中的局部RAS激活导致破骨细胞吸收,导致骨质疏松症。本研究旨在调查大型队列中RASi使用与骨折发生率之间的关联。
    方法:我们采用嵌套病例对照设计来研究RASi使用与新出现的骨折之间的关联。病例定义为2004年1月至2015年12月期间新诊断为骨折的患者。我们使用1:1倾向评分匹配选择了1,049例病例和对照。进行条件logistic回归分析以估计RASi暴露与骨折发生率之间的关联。
    结果:总体而言,RASi的使用与较低的骨折发生率显着相关(曾经使用过的人与从未使用过的人:OR,0.73;95%CI,0.59-0.91)。我们发现,仅使用ARB的用户比从未使用RASi的用户经历更少的骨折(或,0.65;95%CI,0.49-0.86),而仅ACEi的用户或ARB/ACEi曾经的用户则没有。在亚组分析中,RASi-曾经没有脑血管疾病的使用者,BMI超过23且他汀类药物暴露者的OR显著较低.
    结论:本研究建立了使用RASi和减少骨折发生率之间的显著关联,因此突出了RASi作为有骨质疏松性骨折风险的老年患者的预防策略的潜在临床实用性。
    BACKGROUND: The therapeutic efficacy of renin-angiotensin system inhibitors (RASi) in elderly patients with hypertension and at risk of fractures has been in the limelight because of accumulating evidence that localized RAS activation in bone tissue leads to osteoclastic bone resorption, resulting in osteoporosis. This study set out to investigate the association between RASi use and fracture incidence in a large cohort.
    METHODS: We employed a nested case-control design to investigate the association between RASi use and newly developed fractures. A case was defined as a patient newly diagnosed with a fracture between January 2004 and December 2015. We selected 1,049 cases and controls using 1:1 propensity score matching. Conditional logistic regression analysis was conducted to estimate the association between RASi exposure and fracture incidence.
    RESULTS: Overall, RASi usage was significantly associated with lower odds for fracture incidence (ever-users vs never-users: OR, 0.73; 95% CI, 0.59-0.91). We found that ARB-only users experienced fewer fractures than RASi-never users (OR, 0.65; 95% CI, 0.49-0.86), whereas ACEi-only users or ARB/ACEi-ever users did not. In subgroup analysis, RASi-ever users without cerebrovascular disease, those with a BMI exceeding 23, and statin exposure had significantly lower ORs.
    CONCLUSIONS: The present study established a significant association between RASi use and reduced fracture incidence, thus highlighting the potential clinical utility of RASi use as a preventive strategy in elderly patients at risk for osteoporotic fractures.
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