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Background/Objectives: Increasing drugs’ stability and adequately protecting them against degradation will ensure a decrease in their price and broader availability of pharmaceutical substances. This is of great importance, especially for drugs used to treat the most common diseases in the population, such as hypertension. The study examined two newly synthesized substances from the angiotensin I-converting enzyme inhibitor (ACEI) group as potential drugs. ACEIs are among the leading drugs used in the treatment of hypertension in the world. The chemical modifications of the tested substances applied concerned the places most susceptible to degradation. The presented work analyzed the compatibility of new derivatives with selected excipients used in pharmacy. Methods: Thermogravimetric (TGA) and differential thermal analyses (c-DTA) were used as the main methods. In addition, non-thermal methods such as colorimetry analysis, Fourier-transform infrared (FTIR) and UV spectroscopy were used. Results: Based on the conducted studies, it can be concluded that the incompatibility of IND-1 with glucose anhydrous and lactose monohydrate occurs only when the mixture is stored at higher temperatures. For the remaining IND-1 and IND-2 mixtures with excipients, compatibility was demonstrated. Conclusions: The obtained results confirmed the usefulness of the applied thermal analyses (TGA and c-DTA) for assessing the compatibility of the tested potential drugs with excipients. However, in the case of incompatibility reactions of substances occurring under the influence of elevated temperatures, such as the Maillard reaction, it is necessary to use non-thermal methods to obtain the right result.

Introduction This study aimed to evaluate the prognosis of patients with COVID-19 and hypertension who were treated with angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor B (ARB) drugs and to identify key features affecting patient prognosis using an unsupervised learning method. Methods A large-scale clinical dataset, including patient information, medical history, and laboratory test results, was collected. Two hundred patients with COVID-19 and hypertension were included. After cluster analysis, patients were divided into good and poor prognosis groups. The unsupervised learning method was used to evaluate clinical characteristics and prognosis, and patients were divided into different prognosis groups. The improved wild dog optimization algorithm (IDOA) was used for feature selection and cluster analysis, followed by the IDOA-k-means algorithm. The impact of ACEI/ARB drugs on patient prognosis and key characteristics affecting patient prognosis were also analysed. Results Key features related to prognosis included baseline information and laboratory test results, while clinical symptoms and imaging results had low predictive power. The top six important features were age, hypertension grade, MuLBSTA, ACEI/ARB, NT-proBNP, and high-sensitivity troponin I. These features were consistent with the results of the unsupervised prediction model. A visualization system was developed based on these key features. Conclusion Using unsupervised learning and the improved k-means algorithm, this study accurately analysed the prognosis of patients with COVID-19 and hypertension. The use of ACEI/ARB drugs was found to be a protective factor for poor clinical prognosis. Unsupervised learning methods can be used to differentiate patient populations and assess treatment effects. This study identified important features affecting patient prognosis and developed a visualization system with clinical significance for prognosis assessment and treatment decision-making.

Background Guidelines by the National Institute for Health and Care Excellence recommend an angiotensin receptor blocker (ARB) rather than an angiotensin-converting enzyme inhibitor (ACEi) for the treatment of hypertension for people of African and Caribbean descent, due to an increased risk of angioedema associated with ACEi use observed in US trials. However, the effectiveness and risk of these drugs in Black populations in UK routine care is unknown. Methods and findings We applied a reference trial emulation approach to UK Clinical Practice Research Datalink Aurum data (linked with data from Hospital Episode Statistics and Office for National Statistics) to study the comparative effectiveness of ARB and ACEi in ethnic minority groups in England, after benchmarking results against the ONTARGET trial. Approximately 17,593 Black, 30,805 South Asian, and 524,623 White patients receiving a prescription for ARB/ACEi between 1 January 2001 and 31 July 2019 were included with a median follow-up of 5.2 years. The primary composite outcome was cardiovascular-related death, myocardial infarction, stroke, or hospitalisation for heart failure with individual components studied as secondary outcomes. Angioedema was a safety endpoint. We assessed outcomes using an inverse-probability-weighted Cox proportional hazards model for ARB versus ACEi with heterogeneity by ethnicity assessed on the relative and absolute scale. For the primary outcome, 27,327 (18.0%) events were recorded in the ARB group (event rate: 25% per 5.5 person-years) and 80,624 (19.1%) events (event rate: 26% per 5.5 person-years) in the ACEi group. We benchmarked results against ONTARGET and observed hazard ratio (HR) 0.96 (95% CI: 0.95, 0.98) for the primary outcome, with an absolute incidence rate difference (IRD)% of -1.01 (95% CI: -1.42, -0.60) per 5.5 person-years. We found no evidence of treatment effect heterogeneity by ethnicity for the primary outcome on the multiplicative (P.sub.int = 0.422) or additive scale (P.sub.int = 0.287). Results were consistent for most secondary outcomes. However, for cardiovascular-related death, which occurred in 37,554 (6.6%) people, there was strong evidence of heterogeneity on the multiplicative (P.sub.int = 0.002) and additive scale (P.sub.int < 0.001). Compared to ACEi, ARB were associated with more events in Black individuals (HR 1.20 (95% CI: 1.02, 1.40); IRD% 1.07 (95% CI: 0.10, 2.04); number-needed-to-harm (NNH): 93) and associated with fewer events in White individuals (HR 0.91 (95% CI: 0.88, 0.93); IRD% -0.87 (95% CI: -1.10, -0.63); number-needed-to-treat (NNT): 115), and no differences in South Asian individuals (HR 0.97 (95% CI: 0.86, 1.09); IRD% -0.17 (95% CI: -0.87, 0.53)). For angioedema, HR 0.56 (95% CI: 0.46, 0.67) with no heterogeneity for ARB versus ACEi on the multiplicative scale (P.sub.int = 0.306). However, there was heterogeneity on the additive scale (P.sub.int = 0.023). Absolute risks were higher in Black individuals (IRD% -0.49 (95% CI: -0.79, -0.18); NNT: 204) compared with White individuals (IRD% -0.06 (95% CI: -0.09, -0.03); NNT: 1667) and no difference among South Asian individuals (IRD% -0.05 (95% CI: -0.15, 0.05) for ARB versus ACEi. Conclusions These results demonstrate variation in drug effects of ACEi and ARB for some outcomes by ethnicity and suggest the potential for adverse consequences from current UK guideline recommendations for ARB in preference to ACEi for Black individuals., Author(s): Paris J. Baptiste 1,2,*, Angel Y. S. Wong 2, Anna Schultze 2, Catherine M. Clase 3,4, Clémence Leyrat 5, Elizabeth Williamson 5, Emma Powell 2, Johannes F. E. Mann [...]

Dilated cardiomyopathy (DCM) is a rare disease that can lead to serious cardiac complications, especially during pregnancy. In this study, a case of DCM in an advanced pregnancy with no known history of the disease resulting in spontaneous delivery is presented. Pregnancy in patients with DCM may have adverse outcomes because of increased cardiac output and plasma volume. This case demonstrates that pregnancy carries serious risks, particularly in patients with an ejection fraction

Introduction Heart failure (HF) is a complex syndrome that affects millions of people worldwide and leads to significant morbidity and mortality. Sacubitril/valsartan, a combination drug consisting of a neprilysin inhibitor and an angiotensin receptor blocker (ARB), has shown a greater improvement in the prognosis of HF than ACE inhibitors (ACEI) or ARB. Recent studies have found that ACEI/ARB or sacubitril/valsartan can increase flow-mediated dilation (FMD) and reduce pulse wave velocity (PWV), which are independent predictors of cardiovascular events and HF prognosis. The purpose of this study is to assess and compare the effect of sacubitril/valsartan and ACEI/ARB on FMD and PWV using meta-analysis and further provide a reference for the role of sacubitril/valsartan in the treatment of HF.Methods and analysis Clinical randomised controlled trials investigating the effect of sacubitril/valsartan and/or ACEI/ARB on FMD and PWV in patients with HF will be searched in the relevant database, including PubMed, Web of Science, Embase, Cochrane Library and China’s National Knowledge Infrastructure up to January 2024. The outcomes of interest are changes in endothelial function assessed by FMD and changes in arterial stiffness assessed by PWV. The risk of bias was evaluated using the revised Cochrane risk of bias tool for randomised trials (RoB2.0). Review Manager V.5.3 software is used for meta-analysis data synthesis, sensitivity analysis, meta-regression analysis, subgroup analysis and risk of bias assessment. The reporting bias of studies will be evaluated using the funnel plot, in which symmetry will be assessed by Begg’s and Egger’s tests. The evidence quality of the included studies will be evaluated by the Grading of Recommendations Assessment, Development, and Evaluation.Ethics and dissemination This study only analyses research data from the published literature and therefore does not require ethical approval. We will submit the systematic review to a peer-reviewed journal.PROSPERO registration number CRD42024538148.

Background/Objectives: Increasing drugs' stability and adequately protecting them against degradation will ensure a decrease in their price and broader availability of pharmaceutical substances. This is of great importance, especially for drugs used to treat the most common diseases in the population, such as hypertension. The study examined two newly synthesized substances from the angiotensin I-converting enzyme inhibitor (ACEI) group as potential drugs. ACEIs are among the leading drugs used in the treatment of hypertension in the world. The chemical modifications of the tested substances applied concerned the places most susceptible to degradation. The presented work analyzed the compatibility of new derivatives with selected excipients used in pharmacy. Methods: Thermogravimetric (TGA) and differential thermal analyses (c-DTA) were used as the main methods. In addition, non-thermal methods such as colorimetry analysis, Fourier-transform infrared (FTIR) and UV spectroscopy were used. Results: Based on the conducted studies, it can be concluded that the incompatibility of IND-1 with glucose anhydrous and lactose monohydrate occurs only when the mixture is stored at higher temperatures. For the remaining IND-1 and IND-2 mixtures with excipients, compatibility was demonstrated. Conclusions: The obtained results confirmed the usefulness of the applied thermal analyses (TGA and c-DTA) for assessing the compatibility of the tested potential drugs with excipients. However, in the case of incompatibility reactions of substances occurring under the influence of elevated temperatures, such as the Maillard reaction, it is necessary to use non-thermal methods to obtain the right result. [ABSTRACT FROM AUTHOR]

Introduction Advanced chronic kidney disease (CKD) is common among patients with coronary artery disease (CAD), and angiotensin‑converting enzyme inhibitors (ACEI) or angiotensin‑receptor blockers (ARB) can improve cardiac and renal function, but whether ACEI/ARB therapy improves long-term prognosis remains unclear among these high-risk patients. Therefore, this research aimed to investigate the relationship between ACEI/ARB therapy and long-term prognosis among CAD patients with advanced CKD.Methods CAD patients with advanced CKD were included in five hospitals. Advanced CKD was defined as estimated glomerular filtration rate (eGFR)

BACKGROUND: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEi/ARB) improve predialysis outcomes; however, ACEi/ARB are underused in patients transitioning to dialysis. We examined the association of different patterns of predialysis ACEi/ARB use with postdialysis survival and whether potentially modifiable adverse events are associated with lower predialysis ACEi/ARB use. METHODS: This was a historic cohort study of 34,676 US veterans with, and 10,690 without, ACEi/ARB exposure in the 3-year predialysis period who subsequently transitioned to dialysis between 2007 and 2014. Associations of different patterns of predialysis ACEi/ARB use with postdialysis all-cause mortality and with predialysis acute kidney injury and hyperkalemia events were examined using multivariable adjusted regression analyses. RESULTS: The mean age of the cohort was 70 years, 98% were males and 27% were African Americans. Compared to ACEi/ARB nonuse, continuous ACEi/ARB use was associated with lower postdialysis all-cause mortality (adjusted hazard ratio [aHR]; 95% confidence interval [95% CI] 0.87; 0.83-0.92). In analyses modeling the duration of predialysis ACEi/ARB use, ACEi/ARB use of 50%-74% and ≥75% were associated with lower mortality compared to nonuse (adjusted hazard ratio, 95% confidence interval 0.96, 0.92-0.99 and 0.91; 0.88-0.94, respectively), whereas no increase in postdialysis survival was observed with shorter predialysis ACEi/ARB use. Predialysis acute kidney injury was associated with shorter duration (

Abstract Background Sacubitril/valsartan and angiotensin-converting enzyme inhibitor (ACEI)/angiotensin-receptor blocker (ARB) therapies were reported to affect glycaemic control and the development of diabetes mellitus (DM), but the findings are inconsistent. We examined the evidence for the effects of sacubitril/valsartan and ACEI/ARB in DM by conducting a meta-analysis. Methods The Cochrane Central Register of Controlled Trials (The Cochrane Library), Embase, PubMed, and ClinicalTrials.gov were searched for data from randomised clinical trials (RCTs) that evaluated the efficacy of sacubitril/valsartan and ACEI/ARB in patients, as of May 25, 2022. Patients were grouped by their disease background at baseline. The main outcomes were the number of new-onset DM and hypoglycaemia, elevated glycaemia, inadequate DM control, diabetes treatment, and diabetic complications, from baseline to the end of the trials. The risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials (ROB 2). The quality of the evidence was evaluated according to the Recommendations for Assessment, Development, and Evaluation guidelines. The meta-analysis of the incidence of various outcomes was conducted using fixed or random effects models. The results are expressed as binary risk, 95% confidence interval (CI), and relative risk (RR). The Mantel-Haenszel method and Z test were used to determine the overall results and determine the significance of the RR. Results This study included 31 RCTs and 86,809 subjects. Compared with placebo, sacubitril/valsartan treatment significantly reduced the risk of new-onset DM among all patients (RR = 0.78, 95% CI: 0.64–0.95), patients with heart failure (HF) (RR = 0.24, 95% CI: 0.12–0.48), HF with reduced ejection fraction (HFrEF) (RR = 0.24, 95% CI: 0.12–0.50), and HF with preserved ejection fraction (HFpEF) (RR = 0.54, 95% CI 0.34–0.85). In contrast, sacubitril/valsartan treatment significantly increased the risk of hypoglycaemia among all patients (RR = 1.91, 95% CI: 1.05–3.47), patients with not all-DM (defined as part of the study population having DM at baseline) (RR = 5.71, 95% CI: 2.02–16.21), and patients with HFpEF (RR = 7.06, 95% CI: 2.10–23.76). Compared with ACEI/ARB, sacubitril/valsartan treatment significantly increased the risk of hypoglycaemia among patients with HF (RR 1.85, 95% CI 1.12–3.06, p = 0.02) and HFpEF (RR 3.59, 95% CI 1.51–8.55, p = 0.004). Compared with placebo, ACEI/ARB treatment did significantly reduce the risk of new-onset DM among all patients (RR 0.85, 95% CI 0.77–0.93, p = 0.0007) and patients with not all-HF (defined as part of the study population having HF at baseline) (RR 0.87, 95% CI 0.82–0.93, p

Abstract Objective To explore the effects of long-term oral ACEIs/ARBs on the incidence of exacerbation and in-hospital mortality in elderly COVID-19 Omicron BA.2 patients with hypertension, especially patients aged 80 years or older. Materials and methods In this retrospective study, patients suffering mild and rcommon COVID-19 with hypertension who were hospitalized in the Shanghai Fourth People’s Hospital between April 2022 and June 2022 were enrolled. Primary outcomes included the incidence of exacerbation and in-hospital mortality. Secondary outcomes included the incidence of respiratory failure of patients, use of mechanical ventilation, nucleic acid conversion time (NCT), hospitalization costs, and the temporal trend of the incidence of exacerbations and in-hospital mortality in different age groups. The data were analysed using propensity score weighting (PSW). Results In the entire cohort, there were 298 ACEI/ARB users and 465 non-ACEI/ARB users. The ACEI/ARB group showed a lower incidence of exacerbation (OR = 0.64, 95% CI for OR: 0.46–0.89, P = 0.0082) and lower in-hospital mortality (OR = 0.49, 95% CI for OR: 0.27–0.89, P = 0.0201) after PSW. Sensitivity analysis obtained the same results. The results of the subgroup of patients aged 80 years and older obtained a similar conclusion as the whole cohort. Most of the study indicators did not differ statistically significantly in the subgroup of patients aged 60 to 79 years except for rates of mechanical ventilation and respiratory failure. Conclusion Antihypertensive therapy with ACEIs/ARBs might reduce the incidence of exacerbation and in-hospital mortality. The findings of this study support the use of ACEIs/ARBs in COVID-19 patients infected by Omicron BA.2, especially in patients aged 80 years or older with hypertension.

Background: Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) had beneficial effects on clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) in the pre-reperfusion or thrombolytic era. It is unknown if the benefits persist in the contemporary reperfusion era., Objectives: We sought to determine if ACEI/ARB improves clinical outcomes of patients with STEMI in the contemporary reperfusion era according to the reperfusion strategy., Methods: 12596 patients were analyzed from the prospective, nationwide, multicenter China Acute Myocardial Infarction (CAMI) Registry. These patients were classified into the no reperfusion group (n=6004) and the primary percutaneous coronary intervention (PCI) group (n=6592). Two-year all-cause mortality and major adverse cardiac and cerebrovascular events (MACCE) were compared., Results: In the no reperfusion group, ACEI/ARB therapy at discharge may reduce the incidences of 30-day MACCE (4.7% vs 7.4%; adjusted hazard ratio [HR]: 0.67; 95% confidence interval [CI]: 0.53-0.85; P<0.001), stroke (0.5% vs 1.1%; adjusted HR: 0.41; 95% CI: 0.21-0.83; P=0.01), and revascularization (2.1% vs 3.1%; adjusted HR: 0.66; 95% CI: 0.46-0.94; P=0.02) compared to patients not treated with ACEI/ARB. Patients treated with ACEI/ARB also showed a lower rate of two-year MACCE (17.0% versus 19.1%; adjusted HR: 0.87; 95% CI: 0.76-0.99; P=0.04). No differences were observed in the remaining outcomes. In the primary PCI group, no differences were observed for all examined outcomes before and after multivariate adjustments., Conclusions: Treatment with ACEI/ARB at discharge may reduce cardiovascular events in STEMI patients not receiving reperfusion, while no significant benefits were observed in those receiving primary PCI.

AimsPermanent pacemaker implantation (PPI) combined with hypertension leads to a higher risk of new-onset atrial fibrillation (NOAF) for patients. Hence, it is essential to study how to reduce this risk. Currently, the effects of the two common anti-hypertensive drugs, angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) and calcium channel blockers (CCB), on the risk of NOAF for such patients remain unknown. This study aimed to investigate this association.MethodsThis single-center retrospective study included hypertensive patients with PPI and without prior history of AF/atrial flutter, heart valve disease, hyperthyroidism, etc. Patients were classified into ACEI/ARB group and CCB group based on their exposure drug information. The primary outcome was NOAF events that occurred within 12 months after PPI. The secondary efficacy assessments were the changes from baseline to follow-up in blood pressure and transthoracic echocardiography (TTE) parameters. A multivariate logistic regression model was used to verify our aim.ResultsA total of 69 patients were finally included (51 on ACEI/ARB and 18 on CCB). Both univariate analysis [odds ratio (OR) 0.241, 95% confidence interval (CI) 0.078–0.745] and multivariate analysis (OR: 0.246, 95% CI: 0.077–0.792) demonstrated that ACEI/ARB were associated with a lower risk of NOAF compared to CCB. The mean reduction in left atrial diameter (LAD) from baseline was greater in ACEI/ARB group than in CCB group (P = 0.034). There was no statistical difference between groups in blood pressure and other TTE parameters after treatment.ConclusionFor patients with PPI combined with hypertension, ACEI/ARB may be superior to CCB in selecting anti-hypertensive drugs, as ACEI/ARB further reduces the risk of NOAF. One reason for this may be that ACEI/ARB improves left atrial remodelling such as LAD better.

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly used antihypertensive drugs. However, the impact that the use of ACEI and ARB drugs will have on the survival of patients with hypertension and cancer is still unclear. Therefore, the present study aimed to investigate the effects of ACEI and ARB use on the survival of patients with cancer. The Embase, PubMed and Web of Science databases were used to systematically analyze the survival of hypertensive patients with cancer treated with ACEIs or ARBs. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the association between ACEI and ARB use and patient survival. The relationship between the survival of patients with certain types of cancer and ACEI and ARB use was evaluated using the calculated HRs. Patients with ovarian, pancreatic, prostate, hepatocellular, lung, esophageal, gastric, colon, nasopharyngeal, head and neck tumors, gallbladder and rectal cancers that used ACEI and ARB analogs had significantly increased survival times, except for patients with breast cancer (HR, 1.04; 95% CI, 0.90-1.19; P<0.01) and uroepithelial carcinoma (HR, 1.15; 95% CI, 0.69-1.94; P<0.01), who had significantly decreased survival times, when compared with patients who did not use these drugs. Analysis of the relationship between the use of ACEIs or ARBs alone or in combination on the overall survival of hypertensive patients with cancer demonstrated that the use of ACEIs alone (HR, 1.00; 95% CI, 0.93-1.08; P<0.01) did not have a significant effect on the survival of these patients. By contrast, the survival time was increased in hypertensive patients with cancer who used either ARBs alone (HR, 0.89; 95% CI, 0.84-0.94; P<0.01) or a combination of ACEIs and ARBs (HR, 0.84; 95% CI, 0.78-0.91; P<0.01). The present meta-analysis demonstrated the potential effects of ACEI and ARB use on the overall survival of patients with cancer. Therefore, investigation of the underlying mechanisms of action of ACEIs and ARBs, as well as the identification of specific groups of patients who may benefit from these interventions, could potentially lead to novel therapeutic options and improve the prognosis of patients with cancer in the future. [ABSTRACT FROM AUTHOR]

Introduction: Advanced chronic kidney disease (CKD) is common among patients with coronary artery disease (CAD), and angiotensin‑converting enzyme inhibitors (ACEI) or angiotensin‑receptor blockers (ARB) can improve cardiac and renal function, but whether ACEI/ARB therapy improves long-term prognosis remains unclear among these high-risk patients. Therefore, this research aimed to investigate the relationship between ACEI/ARB therapy and long-term prognosis among CAD patients with advanced CKD., Methods: CAD patients with advanced CKD were included in five hospitals. Advanced CKD was defined as estimated glomerular filtration rate (eGFR)<30 ml/min per 1.73 m 2 . Cox regression models and competing risk Fine and Gray models were used to examine the relationship between ACEI/ARB therapy and all-cause and cardiovascular death, respectively., Results: Of 2527 patients, 47.6% population of our cohort was discharged on ACEI/ARB. The overall all-cause and cardiovascular mortality were 38.6% and 24.7%, respectively. Multivariate Cox regression analyses indicated that ACEI/ARB therapy was found to be associated with lower rates of both all-cause mortality (hazard ratio (HR)=0.836, 95% confidence interval (CI): 0.738-0.948, p  = 0.005) and cardiovascular mortality (HR = 0.817, 95%CI: 0.699-0.956, p  = 0.011). In the propensity-matched cohort, the survival benefit was consistent, and significantly better survival was observed for all-cause mortality (HR = 0.856, 95%CI: 0.752-0.974, p  = 0.019) and cardiovascular mortality (HR = 0.830, 95%CI: 0.707-0.974, p  = 0.023) among patients treated with ACEI/ARB., Conclusion: ACEI/ARB therapy showed a better survival benefit among high-risk CAD patients with advanced CKD at long-term follow-up, which manifested that strategies to maintain ACEI/ARB treatment may improve clinical outcomes among these high-risk populations.

Background Renin–angiotensin system inhibitors, both angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, slow progression of mild and moderate chronic kidney disease. However, some evidence suggests that discontinuation of renin–angiotensin system inhibitors in patients with advanced chronic kidney disease might increase estimated glomerular filtration rate or slow its decline. Objective To test the hypothesis that stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, or a combination of both, compared with continuing these treatments, improves or stabilises kidney function in patients with progressive stages 4 or 5 chronic kidney disease based on assessment of kidney function using the modification of diet in renal disease four-variable estimated glomerular filtration rate at 3 years, follow-up. Setting Thirty-seven UK hospitals with kidney services. Design An investigator-led multicentre open-label, randomised controlled trial of 411 participants with advanced (stage 4 or 5) progressive chronic kidney disease. Participants Adult patients with advanced (estimated glomerular filtration rate < 30 ml/minute/1.73 m2) and progressive chronic kidney disease who were receiving either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, or a combination of both. Interventions Participants were randomised in a 1 : 1 ratio using a centralised internet-based system to either discontinue renin–angiotensin system inhibitors (n = 206) or continue renin–angiotensin system inhibitors (n = 205). Main outcome measures The primary outcome was the estimated glomerular filtration rate at 3 years; measurements of estimated glomerular filtration rate made after commencing kidney replacement therapy were excluded. Secondary outcomes included development of end-stage kidney disease or starting kidney replacement therapy, a composite of either a > 50% decline in estimated glomerular filtration rate or commencement of kidney replacement therapy (including end-stage kidney disease), cystatin C, hospitalisations, blood pressure, exercise capacity and quality of life. Cardiovascular events, death and safety were recorded. Results At 3 years, the least-squares mean (± standard error) estimated glomerular filtration rate was 12.6 ± 0.7 ml/minute/1.73 m2 in the discontinuation group and 13.3 ± 0.6 ml/minute/1.73 m2 in the continuation group [difference −0.7, 95% confidence interval (−2.5 to 1.0; p = 0.42)] with a negative value favouring the continuation group. The treatment effect did not differ (heterogeneity) when data were analysed by the pre-specified subgroups. End-stage kidney disease or kidney replacement therapy occurred in 128 (62%) and 115 (56%) participants randomised to the discontinue and continue renin–angiotensin system inhibitor groups, respectively (hazard ratio 1.28, 95% confidence interval 0.99 to 1.65). The numbers of cardiovascular events and deaths observed were similar for those randomised to discontinue (108 events and 20 deaths) or continue (88 events and 22 deaths) renin–angiotensin system inhibitors. Limitations Non-white ethnic backgrounds were poorly represented, limiting the generalisability of our findings. The open-label nature of the trial may have affected clinical care and subjective end points, such as quality of life and exercise capacity. We only included patients who were receiving renin–angiotensin system inhibitors at the time of randomisation, thus excluding those who had already discontinued these agents. Conclusions Discontinuing renin–angiotensin system inhibitors in advanced and progressive chronic kidney disease does not cause a clinically relevant change in estimated glomerular filtration rate or difference in its long-term decline. Future work Future work should focus on updating clinical guidelines. Further analyses, in addition to the prespecified analyses, may be undertaken if new estimated glomerular filtration rate equations are introduced into clinical practice. Subgroup analysis by kidney disease aetiology and gender may be undertaken to look for potential differences in outcome in specific groups. Trial registration This trial is registered as STOP ACEi EudraCT Number, 2013-003798-82; ISRCTN62869767. Funding This award was funded by the Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 11/30/07), a Medical Research Council (MRC) and National Institute for Health and Care Research (NIHR) partnership. This is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 5. See the NIHR Funding and Awards website for further award information. Plain language summary Drugs called angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, together known as renin–angiotensin system inhibitors, are used to treat high blood pressure, slow worsening kidney function and lower the risk of kidney failure (known as end-stage kidney disease which requires treatment with dialysis or kidney transplantation) in patients with early chronic kidney disease. However, we did not know if patients treated with renin–angiotensin system inhibitors and who have progressed to more advanced chronic kidney disease (stage 4 or 5) should stop or continue renin–angiotensin system inhibitors. To determine whether stopping renin–angiotensin system inhibitors in people with advanced chronic kidney disease leads to an improvement or stabilisation of kidney function required a study comparing the outcomes of people who had had these drugs stopped with a group who continued these drugs (the STOP-angiotensin-converting enzyme inhibitors trial). We recruited 411 participants with advanced chronic kidney disease who were receiving renin–angiotensin system inhibitors from 37 kidney units in the UK, and randomly (like flipping a coin) allocated them to either stop or continue renin–angiotensin system inhibitors. We then compared kidney function between the two groups at 3 years. We also assessed whether stopping or continuing renin–angiotensin system inhibitors had an influence on the development of end-stage kidney disease or need for kidney replacement therapy, the number of hospitalisations, blood pressure, quality of life and physical function. We collected data on safety outcomes including death and heart-related events (such as heart attacks). The results of the trial showed no difference in kidney function at 3 years. The number of participants requiring dialysis, or a kidney transplant was also similar, as was the quality of life and physical function between the groups. Deaths and the number of heart events were similar in both groups. This research suggests that there is no benefit in stopping renin–angiotensin system inhibitors in patients with advanced chronic kidney disease. Scientific summary Background Renin–angiotensin system (RAS) inhibitors, both angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB), slow the progression of mild and moderate chronic kidney disease (CKD). However, some evidence suggests that discontinuation of RAS inhibitors in patients with advanced CKD might increase estimated glomerular filtration rate (eGFR) or slow its decline. Primary objective To test the hypothesis that discontinuing ACEi or ARB treatment, or a combination of both, compared with continuing on these treatments, improves or stabilises kidney function in patients with progressive stage 4 or stage 5 CKD based on assessment of kidney function using the modification of diet in renal disease (MDRD) four-variable eGFR at 3 years follow-up. Secondary objectives To test whether in each of the randomised groups. Clinical outcomes The number of participants starting kidney replacement therapy (KRT) (dialysis or transplantation) or sustaining a > 50% decline in eGFR differs. There is a difference in the time taken to reach end-stage kidney disease (ESKD) or need for KRT. Hospitalisation rates from any cause are different. Participant quality of life and well-being [measured using the kidney disease quality of life (KDQoL)-SF™ v1.3 questionnaire] differs. Participant physical function (measured using the 6-minute walk test) differs. Withdrawal of these treatments does not cause excess harm [e.g. increased cardiovascular (CV) events such as heart failure, hypertension, myocardial infarction, stroke] and is not associated with an increase in adverse effects. Participant survival in each group is similar. Blood pressure (BP) control is the same. Cystatin-C levels differ. Mechanistic outcomes There is a change in urine protein excretion [urinary protein-to-creatinine ratio (uPCR)]. Discontinuation of ACEi/ARB affects haemoglobin concentration. Discontinuation of ACEi/ARB affects the requirement for erythropoietin stimulating agents. Methods An investigator-initiated, multicentre, open-label randomised trial where people with advanced and progressive CKD (eGFR < 30 ml/minute/1.73 m2) were randomised to either discontinue or continue RAS inhibitors, and then followed up every 3 months for 3 years. Patients underwent screening at 39 centres in the UK. Adults (≥ 18 years of age) with stage 4 or stage 5 CKD (eGFR, < 30 ml/minute/1.73 m2 of body-surface area) were eligible to participate in the trial if they were not receiving dialysis and had not undergone kidney transplantation. All eligible patients were required to have had a decrease of more than 2 ml/minute/1.73 m2 per year in the eGFR during the previous 2 years and to have been receiving treatment with an ACEi, an ARB, or both for more than 6 months. We calculated the eGFR using the four-variable equation used in the MDRD study, as updated in 2005 (MDRD175). Exclusion criteria included uncontrolled hypertension or a history of myocardial infarction or stroke within the previous 3 months. All the patients provided written informed consent. Patients were randomly assigned in a 1 : 1 ratio to either discontinue or continue RAS inhibitors. Randomisation used a centralised internet-based system with minimisation to ensure balance between groups for the following variables: age (< 65 or ≥ 65 years), eGFR (< 15 or ≥ 15 ml/minute/1.73 m2), diabetes (type 1, type 2, or none), mean arterial pressure (< 100 or ≥ 100 mmHg) and proteinuria [protein-to-creatinine ratio (PCR), < 100 or ≥ 100 mg/mmol]. In the group that discontinued RAS inhibitor, any guideline-recommended antihypertensive agent other than a RAS inhibitor could be used to control BP. In the group that continued RAS inhibitors, the responsible clinician chose the agent and dose of the RAS inhibitor and could combine it with any other guideline-recommended antihypertensive agent. The primary outcome was the eGFR at 3 years as calculated according to the MDRD175 four-variable equation. Secondary outcome measures included the time until the development of ESKD or initiation of KRT; a composite of a decrease of more than 50% in the eGFR, the development of ESKD, or the initiation of KRT; hospitalisation for any cause; measures of cystatin C and BP; quality of life (as measured on the KDQoL 36-Item Short Form Survey, version 1.3); exercise capacity (as assessed by the 6-minute walk test); and CV events and death. At the time of this report, the transfer and processing of samples for cystatin C measurement had not yet occurred, so the results are not provided here. Secondary mechanistic outcomes included measures of haemoglobin and urinary protein excretion (PCR). The trial aimed to recruit 410 patients (205 patients in each trial group) which would provide 80% power to determine a minimum relevant between-group difference in the eGFR of 5 ml/minute/1.73 m2 (alpha level of 0.05), assuming an attrition rate of 20%. This difference represents an effect size of 0.31, with a standard deviation of 16 ml/minute/1.73 m2. The analyses were based on the intention-to-treat principle and were adjusted for the minimisation variables and baseline values. A repeated-measures, mixed-effects linear regression model was used to estimate the between-group difference in eGFR at 3 years. Any measurements of eGFR that were made after patients had initiated dialysis or undergone kidney transplantation were excluded from the primary analysis. To examine the effect of data that were not missing at random, we performed sensitivity analyses by fitting pattern-mixture and joint models for the primary outcome. We also repeated analyses for the primary outcome with the use of two other four-variable equations for the eGFR calculation: the Chronic Kidney Disease Epidemiology Collaboration 2009 equation and the MDRD186 equation. Continuously distributed secondary outcomes, such as BP, were analysed using the same methods as per the primary analysis, but data were not censored at the time of initiation of KRT. Categorical (dichotomous) secondary outcomes were analysed with the use of a Poisson regression model with robust standard errors (SEs) to estimate the relative risk (RR) and 95% confidence interval (CI). A Cox proportional-hazards model was used to calculate hazard ratios (HRs) and 95% CIs for time-to-event outcomes, such as the development of ESKD or the initiation of KRT. Categorical safety outcome measures (i.e. hospitalisation and serious adverse events) were summarised as the percentage of patients with these events. Data collection for kidney outcomes did not distinguish between ESKD and kidney-replacement outcomes (i.e. both outcomes used the same end-point code), although investigators could note the specific outcome. Prespecified subgroup analyses were performed only for the primary outcome according to the minimisation variables. Time and subgroup were included in the model to allow for the possibility of differential changes over time within subgroups, time according to subgroup and the three-way interaction among the variables of treatment, time and subgroup. Although all data were included in the regression models for the subgroup analyses, only estimates of differences at 3 years are presented. All analyses were performed with the use of SAS software, version 9.4 (SAS Institute), and Stata software, version 17 (StataCorp). Results At 3 years, among the 411 patients who underwent randomisation, the least-squares mean (LS-Mean) (±SE) eGFR was 12.6 ± 0.7 ml/minute/1.73 m2 in the discontinuation group and 13.3 ± 0.6 ml/minute/1.73 m2 in the continuation group (difference −0.7, 95% (CI −2.5 to 1.0; p = 0.42) with a negative value favouring the continuation group. End-stage kidney disease or the initiation of KRT occurred in 128 patients (62%) in the discontinuation group and in 115 patients (56%) in the continuation group (HR 1.28, 95% CI 0.99 to 1.65). The number of patients with > 50% decline in eGFR or need to start KRT (including ESKD) was 140/206 (68%) in the discontinue RAS inhibitor group compared to 127/202 (63%) in the continue RAS inhibitor group; RR 1.07, 95% CI 0.94 to 1.22. The number of hospitalisations were similar between the groups; 414 in the stop RAS inhibitor group versus 413 in the continue RAS inhibitor group. The difference in LS-Mean at 3 years for systolic BP was 0 mmHg, 95% CI −4 to 5 mmHg. The results were similar for diastolic BP; 0 mmHg, 95% CI −2 to 3 mmHg. Adverse events were similar in both the discontinuation group and continuation group with respect to CV events (108 vs. 88) and deaths (20 vs. 22). Conclusions Our STOP-ACEi trial showed that discontinuing RAS inhibitors for patients with advanced and progressive CKD does not lead to a clinically relevant change in eGFR or difference in the rate of long-term decline in eGFR, overall or in pre-specified subgroups by age, severity of CKD, diabetes, proteinuria or BP. Numerically more patients who discontinued RAS inhibitors had progression to ESKD or need for KRT, so a larger trial might have shown an advantage to continuing with RAS inhibition. The rate of CV events and death was similar. Systolic and diastolic BP and proteinuria were greater over the first year of follow-up in those randomised to discontinue RAS inhibitors but there was little difference, thereafter, reflecting initiation of antihypertensive agents other than RAS inhibitors. No differences in quality of life or exercise capacity were observed for those who discontinued or continued RAS inhibitors. Our trial lacked sufficient power to investigate the effect of withdrawing RAS inhibitors on CV events or mortality. However, because our trial suggests that there is no advantage in discontinuing RAS inhibitors from the perspective of kidney function, there is little rationale to conduct a larger randomised trial to investigate CV safety. Future work Future work should initially focus on updating clinical guidelines in the UK and potentially worldwide. Further analyses, in addition to the prespecified analyses, may be undertaken if new eGFR equations are introduced into routine clinical practice such as the National Institute for Health and Care Excellence recommended removal of black ethnicity correction factor from the eGFR equation. Consideration of subgroup analysis by aetiology of kidney disease and gender will be considered to look for any potential differences in outcome in specific groups which might warrant future studies. Trial registration This trial is registered as STOP ACEi EudraCT Number, 2013-003798-82; ISTRCTN62869767. Funding This award was funded by the Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 11/30/07), a Medical Research Council (MRC) and National Institute for Health and Care Research (NIHR) partnership. This is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 5. See the NIHR Funding and Awards website for further award information.

The renin-angiotensin-aldosterone (RAAS) system plays a significant role in renal and cardiovascular pathophysiology, since its increased activity is involved in arterial hypertension, heart failure, and kidney disease. ACEIs and ARBs are essential drugs for nephroprotection: they reduce blood pressure values and albuminuria, both related to cardiovascular damage and CKD progression. The nephroprotective effects are evident in both diabetes mellitus and non-diabetic renal disease, and the initial eGFR fall, if not more than 30%, should be considered as a marker of long-term success of renal protection. To optimize the RAAS inhibition salt intake should be strictly controlled, moreover the effective antiproteinuric dose can often be higher than that used as an antihypertensive. In selected and closely monitored cases, it is also possible to consider dual RAAS blockade. Finally, it should be noted that in patients with advanced CKD RAAS inhibition should not be discontinued, either because it does not give any benefit on GFR or because it increases cardiovascular risk., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Introduction: Heart failure (HF) is a complex syndrome that affects millions of people worldwide and leads to significant morbidity and mortality. Sacubitril/valsartan, a combination drug consisting of a neprilysin inhibitor and an angiotensin receptor blocker (ARB), has shown a greater improvement in the prognosis of HF than ACE inhibitors (ACEI) or ARB. Recent studies have found that ACEI/ARB or sacubitril/valsartan can increase flow-mediated dilation (FMD) and reduce pulse wave velocity (PWV), which are independent predictors of cardiovascular events and HF prognosis. The purpose of this study is to assess and compare the effect of sacubitril/valsartan and ACEI/ARB on FMD and PWV using meta-analysis and further provide a reference for the role of sacubitril/valsartan in the treatment of HF., Methods and Analysis: Clinical randomised controlled trials investigating the effect of sacubitril/valsartan and/or ACEI/ARB on FMD and PWV in patients with HF will be searched in the relevant database, including PubMed, Web of Science, Embase, Cochrane Library and China's National Knowledge Infrastructure up to January 2024. The outcomes of interest are changes in endothelial function assessed by FMD and changes in arterial stiffness assessed by PWV. The risk of bias was evaluated using the revised Cochrane risk of bias tool for randomised trials (RoB2.0). Review Manager V.5.3 software is used for meta-analysis data synthesis, sensitivity analysis, meta-regression analysis, subgroup analysis and risk of bias assessment. The reporting bias of studies will be evaluated using the funnel plot, in which symmetry will be assessed by Begg's and Egger's tests. The evidence quality of the included studies will be evaluated by the Grading of Recommendations Assessment, Development, and Evaluation., Ethics and Dissemination: This study only analyses research data from the published literature and therefore does not require ethical approval. We will submit the systematic review to a peer-reviewed journal., Prospero Registration Number: CRD42024538148., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly used antihypertensive drugs. However, the impact that the use of ACEI and ARB drugs will have on the survival of patients with hypertension and cancer is still unclear. Therefore, the present study aimed to investigate the effects of ACEI and ARB use on the survival of patients with cancer. The Embase, PubMed and Web of Science databases were used to systematically analyze the survival of hypertensive patients with cancer treated with ACEIs or ARBs. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the association between ACEI and ARB use and patient survival. The relationship between the survival of patients with certain types of cancer and ACEI and ARB use was evaluated using the calculated HRs. Patients with ovarian, pancreatic, prostate, hepatocellular, lung, esophageal, gastric, colon, nasopharyngeal, head and neck tumors, gallbladder and rectal cancers that used ACEI and ARB analogs had significantly increased survival times, except for patients with breast cancer (HR, 1.04; 95% CI, 0.90-1.19; P<0.01) and uroepithelial carcinoma (HR, 1.15; 95% CI, 0.69-1.94; P<0.01), who had significantly decreased survival times, when compared with patients who did not use these drugs. Analysis of the relationship between the use of ACEIs or ARBs alone or in combination on the overall survival of hypertensive patients with cancer demonstrated that the use of ACEIs alone (HR, 1.00; 95% CI, 0.93-1.08; P<0.01) did not have a significant effect on the survival of these patients. By contrast, the survival time was increased in hypertensive patients with cancer who used either ARBs alone (HR, 0.89; 95% CI, 0.84-0.94; P<0.01) or a combination of ACEIs and ARBs (HR, 0.84; 95% CI, 0.78-0.91; P<0.01). The present meta-analysis demonstrated the potential effects of ACEI and ARB use on the overall survival of patients with cancer. Therefore, investigation of the underlying mechanisms of action of ACEIs and ARBs, as well as the identification of specific groups of patients who may benefit from these interventions, could potentially lead to novel therapeutic options and improve the prognosis of patients with cancer in the future., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Xiao et al.)

Background In this secondary analysis of the STOP-ACEi trial, we explored the impact of discontinuing or continuing renin–angiotensin system inhibitor therapy in people with advanced chronic kidney disease on cystatin C estimated glomerular filtration rate (eGFR). Methods Cystatin C eGFRs were calculated at baseline, 12, 24 and 36 months using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin 2012, European Kidney Function Consortium and CKD-EPI Combined 2021 equations. We excluded samples obtained after the initiation of kidney replacement therapy. Primary analysis used complete case analysis and mixed-effects linear regression model, adjusting for minimization variables, baseline value, time-point and treatment by time interaction. Sensitivity analysis was conducted using a pattern mixture model to account for missing data that was not at random. To model the longitudinal cystatin C data with time-to-event data, a joint model was utilized which incorporated the cystatin C measurements at various time points and accounted for the occurrence of kidney replacement therapy. Results The mean cystatin C eGFRs (CKD-EPI 2012) at baseline were 17.8 mg/L [standard deviation (SD 6.3)] and 17.9 mL/min/1.73 m2 (SD 6.3) in the STOP and CONTINUE arms, respectively. The estimated least squares mean difference at 12 months between STOP and CONTINUE arm was –1.46 [95% confidence interval (CI) –2.39 to –0.52, P = .002]. The estimated least squares mean difference at 24 months was –2.27 (95% CI –3.48 to –1.06, P < .001). The estimated least squares mean difference at 36 months was –1.72 (95% CI –3.48 to 0.03, P = .05). Conclusion Our results are consistent with the primary study's analysis and sensitivity analyses support these findings and provide additional insights. Our findings demonstrate the similarity of creatinine and cystatin eGFR results and therefore support the use of cystatin C as an alternative marker of eGFR in advanced CKD, particularly in those in whom creatinine is likely to be less accurate. [ABSTRACT FROM AUTHOR]

Objective The efficacy of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in the treatment of COVID 19 patients with hypertension remains controversial. This study aimed to explore the therapeutic effects of ACEIs and ARBs in COVID-19 patients with hypertension. Methods A retrospective analysis was conducted on COVID-19 patients with hypertension admitted to the hospital. Patients were divided into ACEI/ARB group (n=18) and non ACEI/ARB group (n=29) based on whether they received ACEI or ARB treatment. Patients were further classified into common and severe types according to disease severity, and clinical characteristics, laboratory test results, imaging data, and clinical outcome parameters were compared and analyzed. Results The median age of all patients was 65.0 years (range: 57.0-69.0 years), with 57.4% being male. 76.6% of patients had a clear history of contact, and the median time from onset to admission was 3.0 days (range: 1.0-7.0 days). The most common clinical manifestations were fever (74.5%), cough (48.9%), fatigue (27.7%), and sputum production (25.5%). There were no significant differences in clinical types between the ACEI/ARB group and non ACEI/ARB group (P > 0.05), and there were no significant differences in baseline clinical characteristics and laboratory test results between the two groups (P > 0.05) . In both groups, severe patients had lower lymphocyte counts and higher lactate dehydrogenase (LDH), C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), and D-dimer levels compared to common patients. On the 15th day of illness, severe patients in the non-ACEI/ARB group had higher LDH, CRP, IL-6, PCT, and D-dimer levels compared to those in the ACEI/ARB group, but the differences between the two groups were not significant (P > 0.05) . There was one death in the non-ACEI/ARB group, and the rest of the patients in both groups recovered and were discharged after treatment. Among all patients, the duration of fever and time to improvement on chest computed tomography (CT) were shorter in the ACEI/ARB group compared to the non ACEI/ARB group, while the length of hospital stay and time to viral nucleic acid conversion were longer in the ACEI/ARB group, but these comparisons were not statistically significant (P > 0.05) . Among common patients, the length of hospital stay, time to viral nucleic acid conversion, and time to improvement on chest CT were higher in the ACEI/ARB group compared to the non-ACEI/ARB group, but only the time to viral nucleic acid conversion was significantly different (P < 0.05) . Conversely, among severe patients, the duration of fever, length of hospital stay, time to viral nucleic acid conversion, and time to improvement on chest CT were higher in the non-ACEI/ARB group compared to the ACEI/ARB group, but the differences were not statistically significant (P > 0.05) . Conclusion ACEI or ARB treatment may shorten the duration of fever, and may have a protective effect on severe COVID-19 patients with hypertension. [ABSTRACT FROM AUTHOR]