BACKGROUND: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEi/ARBs) can cause acute kidney injury under dehydratation or in hemodynamically unstable conditions. Regarding kidney transplantation (KT), the risk of using ACEi/ARBs before surgery is not well established. Therefore, we evaluated the clinical outcomes to determine the effect of preoperative use of ACEi/ARBs on KT.
METHODS: We retrospectively collected 1187 patients who received living-donor KT between January 2017 and December 2021. We conducted a propensity score-matched analysis between the ACEi/ARB(+) and ACEi/ARB(-) groups and evaluated the effects of ACEi/ARBs on delayed graft function, post-KT renal function, hyperkalemia events, rejection, and graft survival.
RESULTS: The ACEi/ARB(+) group showed a similar incidence of delayed graft function as the ACEi/ARB(-) group (1.8% vs. 1.0%, P = 0.362). The risk of delayed graft function was not upregulated in the ACEi/ARB(+) group after propensity score-matching (odds ratio: 0.50, 95% confidence interval (CI) 0.13-2.00). Postoperative creatinine levels and the slope of creatinine levels after KT also were not significantly different between the two groups (creatinine slope from POD#0 to POD#7: - 0.73 ± 0.35 vs. - 0.75 ± 0.32 mg/dL/day, P = 0.464). Hyperkalemia did not occur more often in the ACEi/ARB(+) group than in the ACEi/ARB(-) group during perioperative days. Rejection-free survival (P = 0.920) and graft survival (P = 0.621) were not significantly different between the two groups.
CONCLUSIONS: In KT, the preoperative use of ACEi/ARBs did not significantly affect clinical outcomes including delayed graft function, postoperative renal function, hyperkalemia events, incidence of rejection, and graft survival rates compared to the patients who did not receive ACEi/ARBs.

Anthracyclines and trastuzumab are widely used to treat breast cancer but increase the risk of cardiomyopathy and heart failure. With the use of trastuzumab and anthracycline-containing medications, this study intends to evaluate the effectiveness and security of current treatments against cardiotoxicity. We conducted a systematic review of randomized controlled trials (RCTs), which used at least one angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), or beta-blocker (BB) to prevent cardiotoxicity of antineoplastic agents for breast cancer, in 4 databases (PubMed, Cochrane Library, EMBASE, Web of Science) from inception to 11 May 2022, without language restrictions. The outcome of interest was left ventricular ejection fraction (LVEF) and adverse events. Stata 15 and R software 4.2.1 were used to perform all statistical analyses. The Cochrane version 2 of the risk of bias tool was used to assess the risk of bias, and the grading of recommendations assessment, development, and evaluation (GRADE) assessment was used to appraise the quality of the evidence. Fifteen randomized clinical studies with a total of 1977 patients were included in the analysis. The included studies demonstrated statistically significant LVEF in the ACEI/ARB and BB treatment groups (χ2 = 184.75, I2 = 88.6%, p = 0.000; SMD 0.556, 95% CI 0.299 to 0.813). In an exploratory subgroup analysis, the benefit of experimental agents on LVEF, whether anthracyclines or trastuzumab, was prominent in patients treated with ACEIs, ARBs, and BBs. Compared to placebo, ACEI/ARB and BB treatments in breast cancer patients protect against cardiotoxicity after trastuzumab and anthracycline-containing medication treatment, indicating a benefit for both.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are mainly known as anti-hypertensive drugs. Recent evidence suggests their anti-tumor potential against renal cancer. More than one-fourth of patients present with metastasis on their first visit.
OBJECTIVE: The purpose of the current study was to examine the potential clinical impact of ACEI/ARB on metastatic renal cell carcinoma (mRCC).
METHODS: We searched through several online databases, including Pubmed, Scopus, Web of Science, and Embase, to find clinical studies that have investigated the association between treatment with ACEI/ARB and the survival of patients with mRCC. The hazard ratio (HR) and 95% confidence interval (95% CI) were utilized to assess the strength of the association.
RESULTS: A total of 6 studies with a total number of 2,364 patients were found eligible for the final analysis. The HR for the relationship between ACEI/ARB use and overall survival (OS) showed patients undergoing treatment with ACEI/ARB to have higher OS than non-users (HR: 0.664, 95% CI 0.577-0.764, p=0.000). Furthermore, the HR for the relationship between ACEI/ARB use and progression-free survival (PFS) showed patients undergoing treatment with ACEI/ARB to have higher PFS than non-users (HR: 0.734, 95% CI 0.695-0.794, p=0.000).
CONCLUSIONS: The results of this review offer ACEI/ARB as a potential therapeutic option associated with improved survival outcomes in patients receiving anti-vascular endothelial growth factor therapy.

OBJECTIVE: In acute coronary syndrome (ACS) patients without advanced renal dysfunction [estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2], early (within 24 h of admission) angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) is the guideline-directed medical therapy. The clinical efficacy of early ACEI/ARB therapy among ACS patients with advanced renal dysfunction remains unclear.
RESULTS: Among 184 850 ACS patients hospitalized from July 2014 to December 2018 in the Chinese National Electronic Disease Surveillance System Platform (CNEDSSP) cohort and 113 650 ACS patients enrolled from November 2014 to December 2019 in the Improving Care for Cardiovascular Disease in China-ACS Project (CCC-ACS) cohort, we identified 3288 and 3916 ACS patients with admission eGFR < 30 mL/min/1.73 m2 [2647 patients treated with ACEI/ARB (36.7%)], respectively. After 1:1 propensity score matching (PSM) in each cohort, Kaplan-Meier analysis showed that early ACEI/ARB use was associated with a 39% [hazard ratio (HR): 0.61, 95% confidence interval (95% CI): 0.45-0.82] and a 34% (HR: 0.66, 95% CI: 0.46-0.95) reduction in in-hospital mortality in CNEDSSP and CCC-ACS cohorts, respectively, which was consistent in multiple sensitivity analyses. A random effect meta-analysis of the two cohorts after PSM revealed a 32% reduction (risk ratio: 0.68, 95% CI: 0.55-0.84) in in-hospital mortality among ACEI/ARB users.
CONCLUSIONS: Based on two nationwide cohorts in China in contemporary practice, we demonstrated that ACEI/ARB therapy initiated within 24 h of admission is associated with a reduction in in-hospital mortality in ACS patients with advanced renal dysfunction.
BACKGROUND: CCC-ACS project was registered at URL: https://www.clinicaltrials.gov. (Unique identifier: NCT02306616).

Transcatheter aortic valve replacement (TAVR) has become the standard of care for most patients with severe aortic stenosis (AS), but the impact of medical therapy prescribing patterns on post-TAVR patients has not been thoroughly investigated.
We analyzed Optum claims data from 9,012 adults who received TAVR for AS (January 2014-December 2018). Pharmacy claims data were used to identify patients who filled ACEI/ARB and/or statin prescriptions during the study\'s 90-day landmark period post-TAVR. Kaplan-Meier and adjusted Cox Proportional Hazards models were used to evaluate the association of prescribing patterns with mortality during the 3-year follow-up period. Subgroup analyses were performed to examine the impact of 11 potential confounders on the observed associations.
A significantly lower adjusted 3-year mortality was observed for patients with post-TAVR prescription for ACEI/ARBs (hazard ratio [HR] = 0.82, 95% confidence interval [CI] 0.74-0.91, P = .0003) and statins (HR = 0.85, 95% CI 0.77-0.94, P = .0018) compared to patients who did not fill prescriptions for these medications post-TAVR. Subgroup analyses revealed that the survival benefit associated with ACEI/ARB prescription was not affected by any of the potential confounding variables, except preoperative ACEI/ARB prescription was associated with significantly lower risk of mortality vs postoperative prescription only. No other subgroup variables had significant interactions associated with survival benefits, including preoperative use of statins.
In this large-scale, real-world analysis of patients undergoing TAVR, the prescription of ACEI/ARB and statins was associated with a significantly lower risk of mortality at 3-years, especially in those where the medications were initiated preoperatively.

Newly introduced drugs for heart failure (HF) have been reported to improve the prognosis of HF with preserved ejection fraction (HFpEF) in the lower range of left ventricular ejection fraction (LVEF). We hypothesized that a higher LVEF is related to an unfavourable prognosis in patients with HFpEF.
We tested this hypothesis by analysing the data from a prospective multicentre cohort study in 255 patients admitted to the hospital due to decompensated HF (LVEF > 40% at discharge). The primary endpoint of this study was a composite outcome of all-cause death and readmission due to HF, and the secondary endpoint was readmission due to HF. LVEF and the mitral E/e\' ratio were measured using echocardiography. In multicovariate parametric survival time analysis, LVEF [hazard ratio (HR) = 1.046 per 1% increase, P = 0.001], concurrent atrial fibrillation (AF) (HR = 3.203, P < 0.001), and E/e\' (HR = 1.083 per 1.0 increase, P < 0.001) were significantly correlated with the primary endpoint. In addition to these covariates, angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) use was significantly correlated with the secondary endpoint (HR = 0.451, P = 0.008). Diagnostic performance plot analysis demonstrated that the discrimination threshold value for LVEF that could identify patients prone to reaching the primary endpoint was ≥57.2%. The prevalence of AF or E/e\' ratio did not differ significantly between patients with LVEF ≥ 58% and with 40% < LVEF < 58%.
A higher LVEF is independently related to poor prognosis in patients with HFpEF, in addition to concurrent AF and an elevated E/e\' ratio. ACEI/ARB use, in contrast, was associated with improved prognosis, especially with regard to readmission due to HF.
https://www.umin.ac.jp/ctr/index.htm.
UMIN000017725.

Despite high rates of complications in patients with CKD without diabetes, the implementation of proven therapies in this group remains low. Expressing the clinical benefit of a therapy in terms of extra years free from the disease or death may facilitate implementation. We estimated lifetime survival free of kidney failure for patients with albuminuric CKD without diabetes treated with the combination therapy of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and sodium-glucose cotransporter-2 (SGLT2) inhibitors relative to patients not treated.
We used trial-level estimates of the effect of treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ramipril/benazepril; n=690) and SGLT2 inhibitors (dapagliflozin; n=1398) compared with placebo to derive the effect of combination therapy versus no treatment. Using this effect, we estimated treatment effect of combination therapy to the active treatment group of patients with albuminuric CKD without diabetes participating in the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial (n=697) and projected eventfree and overall survival for those treated and not treated with combination therapy. We also performed our calculations anticipating lower adherence and less pronounced benefits than were observed in the clinical trials. The primary outcome was a composite of doubling of serum creatinine, kidney failure, or death.
The aggregate estimated hazard ratio comparing combination therapy with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and SGLT2 inhibitor versus no treatment for the primary end point was 0.35 (95% confidence interval, 0.30 to 0.41). For a 50-year-old patient until the age of 75 years, the estimated survival free from the primary composite end point was 17.0 (95% confidence interval, 12.4 to 19.6) years with the combination therapy and 9.6 years (95% confidence interval, 8.4 to 10.7) with no treatment with any of these agents, corresponding to a gain in eventfree survival of 7.4 (95% confidence interval, 6.4 to 8.7) years. When assuming lower adherence and less pronounced efficacy of combination therapy, the gain in eventfree survival ranged from 5.3 years (95% confidence interval, 4.4 to 6.1) to 5.8 years (95% confidence interval, 4.8 to 6.8).
Treatment with the combination of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and SGLT2 inhibitor in patients with albuminuric CKD without diabetes is expected to substantially increase kidney failure-free survival.
Benazepril for Advanced Chronic Renal Insufficiency, NCT00270426, and a Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients with Chronic Kidney Disease (Dapa-CKD), NCT03036150.

UNASSIGNED: Few studies have evaluated whether acute myocardial infarction (AMI) patients with relatively low blood pressure benefit from early ACEI/ARB use in the era of percutaneous coronary intervention (PCI).
UNASSIGNED: This study evaluated the associations of ACEI/ARB use within 24 h of admission with in-hospital outcomes among AMI patients with SBP < 100 mmHg and undergoing PCI.
UNASSIGNED: This study was based on the Improving Care for Cardiovascular Disease in China-ACS project, a collaborative registry and quality improvement project of the American Heart Association and the Chinese Society of Cardiology. Between November 2014 and December 2019, a total of 94,623 patients with AMI were enrolled. Of them, 4,478 AMI patients with SBP < 100 mmHg and undergoing PCI but without clinically diagnosed cardiogenic shock at admission were included. Multivariable logistic regression and propensity score-matching analysis were used to evaluate the association between early ACEI/ARB use and in-hospital major adverse cardiac events (MACEs), a combination of all-cause death, cardiogenic shock, and cardiac arrest.
UNASSIGNED: Of AMI patients, 24.41% (n = 1,093) were prescribed ACEIs/ARBs within 24 h of admission. Patients with early ACEI/ARB use had a significantly lower rate of MACEs than those without ACEI/ARB use (1.67% vs. 3.66%, p = 0.001). In the logistic regression analysis, early ACEI/ARB use was associated with a 45% lower risk of MACEs (odds ratio: 0.55, 95% CI: 0.33-0.93; p = 0.027). Further propensity score-matching analysis still showed that patients with early ACEI/ARB use had a lower rate of MACEs (1.96% vs. 3.93%, p = 0.009).
UNASSIGNED: This study found that among AMI patients with an admission SBP < 100 mmHg undergoing PCI, early ACEI/ARB use was associated with better in-hospital outcomes. Additional studies of the early use of ACEIs/ARBs in AMI patients with relatively low blood pressure are warranted.

BACKGROUND: Cardiovascular medications are vital for the secondary prevention of coronary arterial disease (CAD). However, the effect of cardiovascular medication may depend on the optimal adherence of the patients. This meta-analysis aims to determine the magnitude of adherence to vascular medications that influences the absolute and relative risks (RRs) of mortality in patients with CAD in real-world settings.
METHODS: The Cochrane Library, PubMed, and EMBASE databases were searched through March 1, 2022. Prospective studies reporting association as RR and 95% confidence interval between cardiovascular medication adherence and any cardiovascular events and/or all-cause mortality in patients with CAD were included. A one-stage robust error meta-regression method was used to summarize the dose-specific relationships.
RESULTS: A total of 18 studies were included. There is a significant inverse linear association between cardiovascular medication adherence and cardiovascular events (pnonlinearity  = .68) or mortality (pnonlinearity  = .82). The exposure-effect analysis showed that an improvement of 20% cardiovascular medication adherence was associated with 8% or 12% lower risk of any cardiovascular events or mortality, respectively. In subgroup analysis, the benefit was observed in adherence of stain (RR: 0.90, for cardiovascular events, RR: 0.85, for mortality), angiotensin-converting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARB)(RR: 0.90, for mortality), and antiplatelet agent (RR: 0.89 for mortality) but not in beta-blocker (RR: 0.90, p = .14, for cardiovascular events, RR: 0.97, p = .32 for mortality). Estimated absolute differences per 1 million individuals per year for mortality associated with 20% improvement were 175 cases for statin, 129 cases for antiplatelet, and 117 cases for ACEI/ARB.
CONCLUSIONS: Evidence from the real word showed poor adherence to vascular medications contributes to a considerable proportion of all cardiovascular disease events and mortality in patients with CAD.

Chronic kidney disease (CKD) is a global public health problem, and cardiovascular disease is the most common cause of death in patients with CKD. The incidence and prevalence of cardiovascular events during the early stages of CKD increases significantly with a decline in renal function. More than 50% of dialysis patients die from cardiovascular disease, including coronary heart disease, heart failure, arrhythmia, and sudden cardiac death. Therefore, developing effective methods to control risk factors and improve prognosis is the primary focus during the diagnosis and treatment of CKD. For example, the SPRINT study demonstrated that CKD drugs are effective in reducing cardiovascular and cerebrovascular events by controlling blood pressure. Uncontrolled blood pressure not only increases the risk of these events but also accelerates the progression of CKD. A co-crystal complex of sacubitril, which is a neprilysin inhibitor, and valsartan, which is an angiotensin receptor blockade, has the potential to be widely used against CKD. Sacubitril inhibits neprilysin, which further reduces the degradation of natriuretic peptides and enhances the beneficial effects of the natriuretic peptide system. In contrast, valsartan alone can block the angiotensin II-1 (AT1) receptor and therefore inhibit the renin-angiotensin-aldosterone system. These two components can act synergistically to relax blood vessels, prevent and reverse cardiovascular remodeling, and promote natriuresis. Recent studies have repeatedly confirmed that the first and so far the only angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan can reduce blood pressure more effectively than renin-angiotensin system inhibitors and improve the prognosis of heart failure in patients with CKD. Here, we propose clinical recommendations based on an expert consensus to guide ARNI-based therapeutics and reduce the occurrence of cardiovascular events in patients with CKD.