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Protection against death and renal failure by renin-angiotensin system blockers in patients with diabetes and kidney disease.

ABSTRACT: Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are widely used to block the renin-angiotensin system (RAS). Yet it remains uncertain whether these drugs are equally effective and safe. Systematic reviews and meta-analyses of ACEis/ARBs in diabetes and kidney disease published in PubMed, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases were searched for clinical outcomes including all-cause mortality, end-stage renal disease (ESRD), hyperkalemia and cough. Eight meta-analyses included 2177-61,264 patients with follow-up of 6-108 months. RAS blockers reduced mortality (relative risk ratio (RR), 0.90, 95% confidence interval (CI), 0.86-0.95) without heterogeneity. The death protection was significant specifically with ACEis (RR, 0.85, 95% CI, 0.79-0.91), but not with ARBs. Protection against ESRD was homogenously evident by ARBs (RR, 0.79, 95% CI, 0.73-0.87), ACEis (RR, 0.79, 95% , 0.64-0.94), and both (RR, 0.79, 95% CI, 0.73-0.87). Significant side effects were hyperkalemia by ARBs (RR, 2.44, 95% CI, 1.13-5.26), and cough by ACEis (RR, 2.38, 95% CI, 1.75-3.22) CONCLUSIONS: In patients with diabetes and kidney disease, ACEis and ARBs are consistently protective for the development of ESRD. Use of ACEis alone additionally reduces deaths and increases the risk for cough. Use of ARBs alone increases the risk for hyperkalemia without additional benefit of death protection.

SUBMITTER: Shen J

PROVIDER: S-EPMC5843910 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Protection against death and renal failure by renin-angiotensin system blockers in patients with diabetes and kidney disease.

Shen Jian J Huang Yan-Mei YM Song Xin-Nan XN Hong Xue-Zhi XZ Wang Min M Ling Wei W Zhang Xiao-Xi XX Zhao Hai-Lu HL

Journal of the renin-angiotensin-aldosterone system : JRAAS 20160703 3

<h4>Introduction</h4>Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are widely used to block the renin-angiotensin system (RAS). Yet it remains uncertain whether these drugs are equally effective and safe.<h4>Methods</h4>Systematic reviews and meta-analyses of ACEis/ARBs in diabetes and kidney disease published in PubMed, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases were searched for clinical outcomes including all-cause mortal ...[more]

PMID: 27377659

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Project description:Background and objectivesThere is concern about potential deleterious effects of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) in patients with coronavirus disease 2019 (COVID-19). Patients with kidney failure, who often use ACEis/ARBs, are at higher risk of more severe COVID-19. However, there are no data available on the association of ACEi/ARB use with COVID-19 severity in this population.Design, setting, participants, & measurementsFrom the European Renal Association COVID-19 database (ERACODA), we retrieved data on kidney transplant recipients and patients on dialysis who were affected by COVID-19, between February 1 and October 1, 2020, and had information on 28-day mortality. We used Cox proportional-hazards regression to calculate hazard ratios for the association between ACEi/ARB use and 28-day mortality risk. Additionally, we studied the association of discontinuation of these agents with 28-day mortality.ResultsWe evaluated 1511 patients: 459 kidney transplant recipients and 1052 patients on dialysis. At diagnosis of COVID-19, 189 (41%) of the transplant recipients and 288 (27%) of the patients on dialysis were on ACEis/ARBs. A total of 88 (19%) transplant recipients and 244 (23%) patients on dialysis died within 28 days of initial presentation. In both groups of patients, there was no association between ACEi/ARB use and 28-day mortality in both crude and adjusted models (in transplant recipients, adjusted hazard ratio, 1.12; 95% confidence interval [95% CI], 0.69 to 1.83; in patients on dialysis, adjusted hazard ratio, 1.04; 95% CI, 0.73 to 1.47). Among transplant recipients, ACEi/ARB discontinuation was associated with a higher mortality risk after adjustment for demographics and comorbidities, but the association was no longer statistically significant after adjustment for severity of COVID-19 (adjusted hazard ratio, 1.36; 95% CI, 0.40 to 4.58). Among patients on dialysis, ACEi/ARB discontinuation was not associated with mortality in any model. We obtained similar results across subgroups when ACEis and ARBs were studied separately, and when other outcomes for severity of COVID-19 were studied, e.g., hospital admission, admission to the intensive care unit, or need for ventilator support.ConclusionsAmong kidney transplant recipients and patients on dialysis with COVID-19, there was no significant association of ACEi/ARB use or discontinuation with mortality.

Project description:ImportanceFor patients with heart failure with reduced ejection fraction (HFrEF), treatment with sacubitril-valsartan, an angiotensin receptor-neprilysin inhibitor, has become increasingly preferred over angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs). However, sacubitril-valsartan is much more expensive than generic ACE-I/ARBs. It is unknown whether the high cost of sacubitril-valsartan is offset by lower spending on hospitalizations and other treatments.ObjectiveTo compare total and out-of-pocket health care spending among Medicare beneficiaries initiating sacubitril-valsartan vs ACE-I/ARBs for HFrEF.Design, setting, and participantsThis was a cohort study using data from Medicare fee-for-service claims with propensity score matching of Medicare beneficiaries with HFrEF. Data analysis was performed from November 2022 to December 2023.ExposureInitiation of sacubitril-valsartan or an ACE-I/ARB. Patients were matched by propensity score based on 104 covariates, including demographic characteristics, comorbidities, baseline annual spending, and baseline use of health care services.Main outcomes and measuresMean total and out-of-pocket health care expenditures during the 365 days after initiating sacubitril-valsartan or an ACE-I/ARB. Censoring for incomplete follow-up was addressed using Kaplan-Meier probability weighting. Cost differences, cost ratios, and 95% CIs were calculated using a nonparametric bootstrapping method with 500 samples drawn with replacement.ResultsAmong 13 755 matched pairs of Medicare patients with HFrEF (mean [SD] age, 77.5 [7.5] years; 5138 [39%] 80 years or older; 9949 females [36%] and 17 561 males [64%]), mean annual total health care spending per person was similar for sacubitril-valsartan initiators and ACE-I/ARB initiators (difference, $701; 95% CI, -$132 to $1593). Sacubitril-valsartan initiators had higher prescription drug costs (difference, $1911; 95% CI, $1704 to $2113), lower inpatient costs (difference, -$790; 95% CI, -$1468 to -$72), lower outpatient costs (difference, -$330; 95% CI, -$664 to -$11), and higher annual out-of-pocket spending (difference, $109; 95% CI, $13 to $208).Conclusions and relevanceThis cohort study found that Medicare beneficiaries initiating sacubitril-valsartan to treat HFrEF had similar total health care spending as those initiating ACE-I/ARBs; higher prescription drug spending was offset by lower inpatient and outpatient spending. However, sacubitril-valsartan use was associated with higher patient out-of-pocket costs, which may exacerbate health disparities and limit access and affordability.

Project description:IntroductionUse of certain antihypertensive medications has been an area of interest during the COVID-19 pandemic, and several hypotheses have been developed regarding the effects of renin-angiotensin system blockers as well as calcium channel blockers in those infected with COVID-19. We seek to determine the association between exposure to ACEI, ARB, and CCB and outcomes in those admitted to the hospital with COVID-19 infection.MethodsThis retrospective cohort study included 841 adult patients hospitalized with COVID-19 infection at the University of Chicago Medical Center between March 25 and June 22, 2020. Out of these 841, 453 patients had a personal history of hypertension. For the first part, we evaluated primary outcomes of in-hospital mortality and ICU admission in hospitalized COVID-19 patients based on their exposure to particular medications regardless of a personal history of hypertension and compared them with those who were not on these medications. For the second part, we evaluated the aforementioned outcomes in 453 patients with a personal history of hypertension based on their medication exposure. Secondary outcomes of length of stay, readmission rate, and new-onset dialysis requirement were also compared across the study groups.ResultsOut of 841 patients, 111 (13.19%) were on ACEI/ARB (median age: 66.1, SD 15.4; 52.25% females) and 730 (86.80%) were not on them (median age: 56.6, SD 20.3; 50.14% females), while 277 (32.93%) used CCB (median age: 64.6, SD 15.2; 57.04% females) and 564 (67.06%) did not use CCB (median age: 54.6, SD 21.2; 47.16% females). After adjusting for demographics and covariates, neither ACEI/ARB nor CCB exposure was associated with any effect on mortality, but ACEI/ARB exposure was associated with 42% reduction in risk of ICU admissions (OR 0.58, 95% CI [0.35, 0.95], p value 0.03). In addition, combined use of ACEI/ARB and CCB was associated with statistically significant (45%) reduction in ICU admission (OR 0.55, 95% CI [0.32, 0.94], p value 0.029). Out of 453 patients with a personal history of hypertension, 85 (18.76%) were taking ACEI/ARB (median age 65, SD 15.6; 56.47% females) and 368 (81.24%) were not on ACEI/ARB (median age 62.8, SD 16.4; 54.89% females), while 208 (45.92%) out of 453 were on CCB (median age 65; SD 14.8; 60.1% females) and 245 (54.08%) were not on CCB (median age 61.7, SD 17.3; 51.02% females). In the fully adjusted model in this group, ACEI use was associated with 71% reduction in in-house mortality (OR 0.29, 95% CI [0.09, 0.93], p value 0.03).Discussion/conclusionAmong all hospitalized patients with COVID-19 infection, exposure to ACEI/ARB, as well as combined exposure to ACEI/ARB and CCB, were associated with reduced incidence of ICU admissions. In those admitted patients who had a personal history of hypertension, there was a trend towards reduced in-hospital mortality in those exposed to ACEI.

Project description:Background and purposeMitochondrial dysfunction plays a role in the progression of cardiovascular diseases including heart failure. 3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins), which inhibit ROS synthesis, show cardioprotective effects in chronic heart failure. However, the beneficial role of statins in mitochondrial protection in heart failure remains unclear.Experimental approachRats were treated with angiotensin II (1.5 mg·kg-1 ·day-1 ) or co-administered simvastatin (oral, 10 mg·kg-1 ) for 14 days; and then administration was stopped for the following 14 days. Cardiac structure/function was examined by wheat germ agglutinin staining and echocardiography. Mitochondrial morphology and the numbers of lipid droplets, lysosomes, autophagosomes, and mitophagosomes were determined by transmission electron microscopy. Human cardiomyocytes were stimulated, and intracellular ROS and mitochondrial membrane potential (ΔΨm ) changes were measured by flow cytometry and JC-1 staining, respectively. Autophagy and mitophagy-related and mitochondria-regulated apoptotic proteins were identified by immunohistochemistry and western blotting.Key resultsSimvastatin significantly reduced ROS production and attenuated the disruption of ΔΨm . Simvastatin induced the accumulation of lipid droplets to provide energy for maintaining mitochondrial function, promoted autophagy and mitophagy, and inhibited mitochondria-mediated apoptosis. These findings suggest that mitochondrial protection mediated by simvastatin plays a therapeutic role in heart failure prevention by modulating antioxidant status and promoting energy supplies for autophagy and mitophagy to inhibit mitochondrial damage and cardiomyocyte apoptosis.Conclusion and implicationsMitochondria play a key role in mediating heart failure progression. Simvastatin attenuated heart failure, induced by angiotensin II, via mitochondrial protection and might provide a new therapy to prevent heart failure.

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Protection against death and renal failure by renin-angiotensin system blockers in patients with diabetes and kidney disease.

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Protection against death and renal failure by renin-angiotensin system blockers in patients with diabetes and kidney disease.

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