Renin-angiotensin System Blockers Research Articles

Screening and management of hypertensive patients with chronic kidney disease referred to Hypertension Excellence Centres among 27 countries. A pilot survey based on questionnaire.

Real-life management of hypertensive patients with chronic kidney disease (CKD) is unclear. A survey was conducted in 2023 by the European Society of Hypertension (ESH) to assess management of CKD patients referred to ESH-Hypertension Excellence Centres (ESH-ECs) at first referral visit. The questionnaire contained 64 questions with which ESH-ECs representatives were asked to estimate preexisting CKD management quality. Overall, 88 ESH-ECs from 27 countries participated (fully completed surveys: 66/88 [75.0%]). ESH-ECs reported that 28% (median, interquartile range: 15-50%) had preexisting CKD, with 10% of them (5-30%) previously referred to a nephrologist, while 30% (15-40%) had resistant hypertension. The reported rate of previous recent (<6 months) estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) testing were 80% (50-95%) and 30% (15-50%), respectively. The reported use of renin-angiotensin system blockers was 80% (70-90%). When a nephrologist was part of the ESH-EC teams the reported rates SGLT2 inhibitors (27.5% [20-40%] vs. 15% [10-25], P = 0.003), GLP1-RA (10% [10-20%] vs. 5% [5-10%], P = 0.003) and mineralocorticoid receptor antagonists (20% [10-30%] vs. 15% [10-20%], P = 0.05) use were greater as compared to ESH-ECs without nephrologist participation. The rate of reported resistant hypertension, recent eGFR and UACR results and management of CKD patients prior to referral varied widely across countries. Our estimation indicates deficits regarding CKD screening, use of nephroprotective drugs and referral to nephrologists before referral to ESH-ECs but results varied widely across countries. This information can be used to build specific programs to improve care in hypertensives with CKD.

Dihydropyridine Calcium Channel Blockers and Kidney Outcomes.

Early trials of dihydropyridine calcium channel blockers (DCCBs) suggest a detrimental effect on intraglomerular pressure and an association with albuminuria. We sought to evaluate the associations of DCCB initiation with albuminuria and kidney failure with replacement therapy (KFRT) and to determine whether renin-angiotensin system (RAS) blockade modified these associations. We conducted a target trial emulation study using a new user, active comparator design and electronic health record data from Geisinger Health. We included patients without severe albuminuria or KFRT who were initiated on a DCCB or thiazide (active comparator) between January 1, 2004, and December 31, 2019. Using inverse probability of treatment weighting, we performed doubly robust Cox proportional hazards regression to estimate the association of DCCB initiation with incident severe albuminuria (urine albumin to creatinine ratio > 300 mg/g) and KFRT, overall and stratified by RAS blocker use. There were 11,747and 26,758 eligible patients initiating a DCCB and thiazide, respectively, with a weighted baseline mean age of 60 years, systolic blood pressure of 143 mm Hg, and eGFR of 86 mL/min/1.73 m2, and with a mean follow-up of 8 years. Compared with thiazides, DCCBs were significantly associated with the development of severe albuminuria (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.16-1.43), with attenuation of risk in the presence of RAS blockade (P for interaction < 0.001). The risk of KFRT was increased among patients without RAS blockade (HR, 1.66; 95% CI, 1.19-2.31), but not with RAS blockade (P for interaction = 0.005). DCCBs were associated with increased risk of albuminuria and, in the absence of RAS blockade, KFRT. These findings suggest coupling DCCB therapy with RAS blockade may mitigate adverse kidney outcomes.

Subtype Identification of Surgically Curable Primary Aldosteronism During Treatment With Mineralocorticoid Receptor Blockade.

Current guidelines and consensus documents recommend withdrawal of mineralocorticoid receptor antagonists (MRAs) before primary aldosteronism (PA) subtyping by adrenal vein sampling (AVS), but this practice can cause severe hypokalemia and uncontrolled high blood pressure. Our aim was to investigate if unilateral PA can be identified by AVS during MRA treatment. We compared the rate of unilateral PA identification between patients with and without MRA treatment in large data sets of patients submitted to AVS while off renin-angiotensin system blockers and β-blockers. In sensitivity analyses, the between-group differences of lateralization index values after propensity score matching and the rate of unilateral PA identification in subgroups with undetectable (≤2 mUI/L), suppressed (<8.2 mUI/L), and unsuppressed (≥8.2 mUI/L) direct renin concentration levels were also evaluated. Plasma aldosterone concentration, direct renin concentration, and blood pressure values were similar in non-MRA-treated (n=779) and MRA-treated (n=61) patients with PA, but the latter required more antihypertensive agents (P=0.001) and showed a higher rate of adrenal nodules (82% versus 67%; P=0.022) and adrenalectomy (72% versus 54%; P=0.01). However, they exhibited no significant differences in commonly used AVS indices and the area under the receiving operating characteristic curve of lateralization index, both under unstimulated conditions and postcosyntropin. Several sensitivity analyses confirmed these results in propensity score matching adjusted models and in patients with undetectable, or suppressed or unsuppressed renin levels. At doses that controlled blood pressure and potassium levels, MRAs did not preclude the identification of unilateral PA at AVS. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01234220.

Effect of angiotensin-converting enzyme inhibitors versus that of angiotensin receptor blockers on survival in patients undergoing hemodialysis: a nationwide observational cohort study

Background This study aimed to evaluate the patient survival rates based on the use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) in a large cohort of patients undergoing maintenance hemodialysis (HD). Methods Data from a national HD quality assessment program were used in this retrospective study. The patients were classified into four groups based on the use of renin-angiotensin system blockers (RASBs) as follows: No group, patients without a prescription of any anti-hypertensive drugs including RASBs; Other group, patients with a prescription of anti-hypertensive drugs excluding RASBs; ACEI group, patients with a prescription of an ACEI; and ARB group, patients with a prescription of an ARB. Results The 5-year survival rates in the no, other, ACEI, and ARB groups were 68.6%, 67.8%, 70.6%, and 69.2%, respectively. The ACEI group had the best patient survival trend among the four groups. In multivariable Cox regression analyses, no differences were observed between the ACEI and ARB groups. Among young patients and patients without diabetes or heart disease, the ACEI group had the best patient survival among the four groups. However, among patients with DM or heart disease, the ARB group had the best patient survival. Conclusions Our study found that patients receiving ACEI and ARB had comparable survival. However, patients receiving ARB had better survival in the subgroups of patients with DM or heart disease, and patients receiving ACEI had better survival in the subgroup of young patients or patients without diabetes or heart disease.

2023 Diabetic Kidney Disease Fact Sheet in Korea.

To investigate the prevalence, incidence, comorbidities, and management status of diabetic kidney disease (DKD) and diabetes-related end-stage kidney disease (ESKD) in South Korea. We used the Korea National Health and Nutrition Examination Survey data (2019 to 2021, n=2,665) for the evaluation of prevalence, comorbidities, control rate of glycemia and comorbidities in DKD, and the Korean Health Insurance Service-customized database (2008 to 2019, n=3,950,857) for the evaluation of trends in the incidence and prevalence rate of diabetes-related ESKD, renin-angiotensin system (RAS) blockers and sodium glucose cotransporter 2 (SGLT2) inhibitors use for DKD, and the risk of atherosclerotic cardiovascular disease (ASCVD) and mortality according to DKD stages. DKD was defined as albuminuria or low estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 in patients with diabetes mellitus. The prevalence of DKD was 25.4% (albuminuria, 22.0%; low eGFR, 6.73%) in patients with diabetes mellitus aged ≥30 years. Patients with DKD had a higher rate of comorbidities, including hypertension, dyslipidemia, and central obesity; however, their control rates were lower than those without DKD. Prescription rate of SGLT2 inhibitors with reduced eGFR increased steadily, reaching 5.94% in 2019. Approximately 70% of DKD patients were treated with RAS blockers. The prevalence rate of diabetesrelated ESKD has been steadily increasing, with a higher rate in older adults. ASCVD and mortality were significantly associated with an in increase in DKD stage. DKD is prevalent among Korean patients with diabetes and is an independent risk factor for cardiovascular morbidity and mortality, which requiring intensive management of diabetes and comorbidities. The prevalence of diabetes-related ESKD has been increasing, especially in the older adults, during past decade.

Effect of Renin-Angiotensin System Blockers in Acute Myocardial Infarction Patients with Acute Kidney Injury.

Renin-angiotensin system blockers (RASBs) are known to improve mortality after acute myocardial infarction (AMI). However, there remain uncertainties regarding treatment with RASBs after AMI in patients with renal dysfunction and especially in the setting of acute kidney injury (AKI). Patients from a multicenter AMI registry undergoing percutaneous coronary intervention in Korea were stratified and analyzed according to the presence of AKI, defined as an increase in serum creatinine levels of ≥0.3 mg/dL or ≥50% increase from baseline during admission, and RASB prescription at discharge. The primary outcome of interest was 5-year all-cause mortality. In total 9,629 patients were selected for initial analysis, of which 2,405 had an episode of AKI. After adjustment using multivariable Cox regression, treatment with RASBs at discharge was associated with decreased all-cause mortality in the entire cohort (hazard ratio [HR] 0.849, confidence interval [CI] 0.753-0.956), but not for the patients with AKI (HR 0.988, CI 0.808-1.208). In subgroup analysis, RASBs reduced all-cause mortality in patients with stage I AKI (HR 0.760, CI 0.584-0.989) but not for stage II and III AKI (HR 1.200, CI 0.899-1.601, interaction p value 0.002). Similar heterogeneities between RASB use and AKI severity were also observed for other clinical outcomes of interest. Treatment with RASBs in patients with AMI and concomitant AKI is associated with favorable outcomes in non-severe AKI, but not in severe AKI. Further studies to confirm these results and to develop strategies to minimize the occurrence of adverse effects arising from RASB treatment are needed.

Glomerular hyperfiltration as a therapeutic target for CKD.

The global burden of chronic kidney disease (CKD) is high and increasing. Early diagnosis and intervention are key to improve outcomes. Single nephron glomerular hyperfiltration is an early pathophysiologic manifestation of CKD that may result in absolute glomerular hyperfiltration, i.e. a high glomerular filtration rate (GFR) or be associated with normal or low GFR because of nephron loss (relative glomerular hyperfiltration). Even though compensatory glomerular hyperfiltration may contribute to maintain kidney function after loss of kidney mass, the associated increased glomerular capillary pressure and glomerular and podocyte size drive podocyte loss, albuminuria and proximal tubular overload, contributing to CKD progression. In this regard, all kidney protective drugs in clinical use so far, from renin-angiotensin system blockers to mineralocorticoid receptor blockers to sodium-glucose cotransporter-2 inhibitors to tolvaptan, induced an early dip in glomerular filtration that is thought to represent reversal of hyperfiltration. As glomerular hyperfiltration may be present early in the course of kidney disease, its recognition may provide an effective intervention window that may predates current criteria based on high albuminuria or loss of GFR. Nevertheless, there is no diagnostic method with high sensitivity and specificity to identify single nephron glomerular hyperfiltration, except when it leads to obvious absolute glomerular hyperfiltration, as observed in the early stages of diabetic kidney disease when nephron mass is still preserved. We now review the concept of glomerular hyperfiltration as an indicator of CKD risk, including definitions, challenges in diagnosis and evaluation, underlying pathophysiological mechanisms, potential therapeutic approaches and unanswered questions.

Impact of Multidisciplinary Heart Failure Clinic on Guideline-Directed Medical Therapy and Clinical Outcomes.

Heart failure (HF) is associated with recurrent hospital admissions and high mortality. Guideline-directed medical therapy has been shown to improve prognosis for patients who have HF with reduced ejection fraction (HFrEF). Despite the proven benefits of guideline-directed medical therapy, its utilization is less than optimal among patients with HF in Malaysia. To determine the impact of a multidisciplinary team HF (MDT-HF) clinic on the use of guideline-directed medical therapy and patients' clinical outcomes at 1 year. This retrospective study was conducted in a single cardiac centre in Malaysia. Patients with HFrEF who were enrolled in the MDT-HF clinic between November 2017 and June 2020 were compared with a matched control group who received the standard of care. Data were retrieved from the hospital electronic system and were analyzed using statistical software. A total of 54 patients were included in each group. Patients enrolled in the MDT-HF clinic had higher usage of renin-angiotensin system blockers (54 [100%] vs 47 [87%], p < 0.001) and higher attainment of the target dose for these agents (35 [65%] vs 5 [9%], p < 0.001). At 1 year, the mean left ventricular ejection fraction (LVEF) was significantly greater in the MDT-HF group (35.7% [standard deviation 12.3%] vs 26.2% [standard deviation 8.7%], p < 0.001), and care in the MDT-HF clinic was significantly associated with better functional class, with a lower proportion of patients categorized as having New York Heart Association class III HF at 1 year (1 [2%] vs 14 [26%], p = 0.001). Patients in the MDT-HF group also had a significantly lower rate of readmission for HF (4 [7%] vs 32 [59%], p < 0.001). Patients who received care in the MDT-HF clinic had better use of guideline-directed medical therapy, greater improvement in LVEF, and a lower rate of readmission for HF at 1 year relative to patients who received the standard of care.

Molecular mechanism and intervention measures of microvascular complications in diabetes.

In this article, the epidemiology, molecular mechanism of occurrence and development, risk factors, and treatment of diabetic microvascular complications such as diabetic nephropathy, diabetic retinopathy, and diabetic peripheral neuropathy were discussed, providing the theoretical basis for more accurate elucidation of the pathogenesis and treatment of diabetic microvascular complications. The electronic database of PubMed was searched, and retrieved papers were screened for eligibility by two independent reviewers. Data were extracted using a standardized data extraction form and the quality of included papers was assessed. Thirty-eight articles were included. Diabetes nephropathy, diabetes peripheral neuropathy, and diabetes retinopathy are the most common and serious microvascular complications of diabetes in clinical patients. Renin-angiotensin system blockers, beta drugs, statins, antivascular endothelial growth factor drugs, and antioxidants can inhibit the occurrence of microvascular complications in diabetes. However, there has been no breakthrough in the treatment of diabetic microvascular complications. Therefore, prevention of diabetic microvascular complications is more important than treatment.

Myocardial injury and myocardial infarction in hypertensive emergency patients; systematic review

This systematic review aimed to determine the prevalence of myocardial injury, myocardial infarction (MI), and its subtypes in individuals presenting with hypertensive emergency. To find all pertinent published articles from 2017 to 2023 that reported studies on the prevalence of hypertensive emergencies and hypertension-mediated organ damage from inception to the date of database search were included. A systematic search of the Web of Science, PubMed, and MEDLINE databases was conducted. Finally eight articles were selected for the review. The authors collaborated using Google Sheets and Google Documents. Of the selected studies, three were retrospective, two were cross sectional, and three were prospective. In men admitted for hypertensive crises, psychomotor agitation and the burden of cardiovascular risk were much higher. Around one-third of patients experiencing hypertensive crises had elevated cardiac troponin, which can be used to identify individuals who are at a greater risk of death early and to provide important prognostic information. A lower BMI was associated with lower initial and serial troponin levels; this obesity paradox was especially prominent in older and female individuals. Three main factors that contributed to hypertensive emergencies (HE) and urgencies (HU) were stress, excessive salt consumption, and non-compliance. Renin-angiotensin system blockers seemed to be the cornerstone of therapy. The case fatality rate for patients undergoing hypertensive episodes was quite significant.

The concomitant use of the renin-angiotensin system inhibitors and survival outcomes of patients with pancreatic adenocarcinoma: an analysis from a tertiary center.

The limited efficacy of chemotherapy in improving survival in pancreatic ductal adenocarcinoma (PDAC) necessitates the exploration of novel strategies to overcome treatment resistance. This study aimed to investigate the impact of combining renin-angiotensin system (RAS) blockers with chemotherapy on survival outcomes in patients with PDAC. Patients with PDAC were enrolled in the retrospective study. We analyzed patients with PDAC (n = 384) at our institution between 2014 and 2021. Survival outcomes, including event-free survival (EFS) and overall survival (OS), were analyzed according to the concomitant use of RAS blockers. Among the 384 patients in the study, 70 (18.2%) concomitantly received angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). Patients in the ACEI/ARB group, characterized by older age and more comorbidities, displayed a significantly superior 12-month EFS rate (22.86% versus 13.69%, p = 0.008) compared to the non-ACEI/ARB group, while OS remained similar between the groups. In the multivariate analysis, the use of ACEI/ARB was associated with better 12-month EFS (hazards ratio = 0.71, 95% confidence interval: 0.52-0.96; p = 0.024). Poor performance, advanced disease status, and higher CA19-9 levels were associated with poor survival outcomes. Concomitant use of ACEIs/ARBs in patients with pancreatic cancer resulted in significantly better 12-month EFS. Age, performance status, disease status, and higher CA19-9 levels were independent predictors of survival. The combination strategy might provide better treatment outcomes in patients with PDAC.

Antihypertensive prescribing patterns in non-dialysis dependent chronic kidney disease: Findings from the Salford Kidney Study.

Hypertension is commonly observed in patients living with chronic kidney disease (CKD). Finding an optimal treatment regime remains challenging due to the complex bidirectional cause-and-effect relationship between hypertension and CKD. There remains variability in antihypertensive treatment practices. To analyze data from the Salford Kidney Study database in relation to antihypertensive prescribing patterns amongst CKD patients. The Salford Kidney Study is an ongoing prospective study that has been recruiting CKD patients since 2002. All patients are followed up annually, and their medical records including the list of medications are updated until they reach study endpoints [starting on renal replacement therapy or reaching estimated glomerular filtration rate (eGFR) expressed as mL/min/1.73 m2 ≤ 10 mL/min/1.73 m2, or the last follow-up date, or data lock on December 31, 2021, or death]. Data on antihypertensive prescription practices in correspondence to baseline eGFR, urine albumin-creatinine ratio, primary CKD aetiology, and cardiovascular disease were evaluated. Associations between patients who were prescribed three or more antihypertensive agents and their clinical outcomes were studied by Cox regression analysis. Kaplan-Meier analysis demonstrated differences in survival probabilities. Three thousand two hundred and thirty non-dialysis-dependent CKD patients with data collected between October 2002 and December 2019 were included. The median age was 65 years. A greater proportion of patients were taking three or more antihypertensive agents with advancing CKD stages (53% of eGFR ≤ 15 mL/min/1.73 m2 vs 26% of eGFR ≥ 60 mL/min/1.73 m2, P < 0.001). An increased number of patients receiving more classes of antihypertensive agents was observed as the urine albumin-creatinine ratio category increased (category A3: 62% vs category A1: 40%, P < 0.001), with the upward trends particularly noticeable in the number of individuals prescribed renin angiotensin system blockers. The prescription of three or more antihypertensive agents was associated with all-cause mortality, independent of blood pressure control (hazard ratio: 1.15; 95% confidence interval: 1.04-1.27, P = 0.006). Kaplan-Meier analysis illustrated significant differences in survival outcomes between patients with three or more and those with less than three antihypertensive agents prescribed (log-rank, P < 0.001). Antihypertensive prescribing patterns in the Salford Kidney Study based on CKD stage were consistent with expectations from the current United Kingdom National Institute of Health and Care Excellence guideline algorithm. Outcomes were poorer in patients with poor blood pressure control despite being on multiple antihypertensive agents. Continued research is required to bridge remaining variations in hypertension treatment practices worldwide.

Hypertension treatment in sub-Saharan Africa: a systematic review.

Sub-Saharan Africa (SSA) faces the highest rate of hypertension worldwide. Blood pressure (BP) control rests on the association of lifestyle modification and antihypertensive medicines. We aimed to systematically review antihypertensive strategies implemented in SSA to achieve BP control. A systematic search beginning in 2003 was performed in MEDLINE, COCHRANE and EMBASE. We included only original and observational studies in SSA countries. Thirty studies were included from 11 countries. No study was multinational. The number of patients varied from 111 to 897 (median: 294; IQR: 192-478). Overall, 21% of patients received monotherapy, 42.6% two-drug and 26.6% three-drug combinations. Out of all the strategies, renin-angiotensin system (RAS) blockers were mostly prescribed, followed by diuretics and calcium channel blockers. In monotherapy, RAS blockers were the first to be prescribed. Only 10 articles described antihypertensive strategies beyond triple combinations. BP control was highly variable (range: 16.4 to 61.2%). Multicentre studies performed in several SSA countries are needed to ensure international guidelines actually do improve outcomes in SSA.

The Use of Renin-Angiotensin System Blockades Among Patients with Chronic Kidney Disease

Background and objectives: Hypertension is common in adult patients with chronic kidney disease with a prevalence that depends on the stage and etiology of chronic kidney disease and has been reported to range from 60-90%. The aim of this study was to evaluate the clinical use of renin angiotensin system blockers in chronic kidney disease patients and to identify their potential indications, contraindications and side effects amongst different clinical specialties in relation to their clinical outcomes. Methods: This study was a descriptive cross sectional based on self-administered online questionnaire, 133 medical doctors from different specialties including nephrologists, internists, urologists, general practitioners responded to the questionnaire and filled it up, which was composed of three main parts including the socio-demographic data of the participants, data about CKD and its stages and finally the RAS blockades. The study extended from June until July 2021. Results: The mean age ± standard deviation of respondents was 44.65 ± 6.89 years. Nearly one third of the respondents were internist, 12.8% nephrologist, 7.5% urologist and 45.9% from other different specialties. The vast majority (98.5%) of the physicians thought that renin angiotensin system inhibitors are effective anti-hypertensive agents even for chronic kidney disease patients. Most of the nephrologists and other specialties would continue the renin angiotensin system inhibitors while most of the internists and urologists would either stop or change the renin angiotensin system inhibitors, this was statistically significant and p–value was 0.010.

Renal safety and survival among acutely ill hospitalized patients treated by blockers of the Renin-Angiotensin axis or loop diuretics: a single-center retrospective analysis

Background Concern exists regarding the renal safety of blocking the renin-angiotensin system (RAS) during acute illness, especially in the presence of volume depletion and hemodynamic instability. Methods We explored the impact of loop diuretics and RAS blockers on the likelihood of developing acute kidney injury (AKI) or acute kidney functional recovery (AKR) among inpatients. Adjusted odds ratio for AKI, AKR and mortality was calculated, using logistic regression models, with subgroup analysis for patients with estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2, corrected for blood pressure measurements. Results 53,289 patients were included. RAS blockade was associated with reduced adjusted odds ratio for both AKI (0.76, CI 0.70–0.83) AKR (0.55, 0.52–0.58), and mortality within 30 days (0.44, 0.41–0.48), whereas loop diuretics were associated with increased risk of AKI (3.75, 3.42–4.12) and mortality (1.71, 1.58–1.85) and reduced AKR (0.71, 0.66–0.75). Comparable impact of RAS blockers and loop diuretics on renal outcomes and death was found among 6,069 patients with eGFR < 30 ml/min/1.73m2. RAS inhibition and diuretics tended to increase the adjusted odds ratios for AKI and to reduce the likelihood of AKR in hypotensive patients. Conclusions Reduced blood pressure, RAS blockers and diuretics affect the odds of developing AKI or AKR among inpatients, suggesting possible disruption in renal functional reserve (RFR). As long as blood pressure is maintained, RAS inhibition seems to be safe and renoprotective in this population, irrespective of kidney function upon admission, and is associated with reduced mortality.

Abstract 16652: Cardiovascular Outcomes of Renin-Angiotensin System Inhibition Amongst Non-Proteinuric Chronic Kidney Disease Patients in the Chronic Renal Insufficiency Cohort

Introduction: Chronic kidney disease is a leading cause of CVD morbidity and mortality. The majority of CKD patients do not have proteinuria. Current therapies, including renin-angiotensin system (RAS) blockers, are only known to be beneficial in proteinuric CKD. Our goal was to evaluate the association of RAS blockade with long-term CVD outcomes and survival among those with non-proteinuric CKD. Methods: The cohort included subjects in the prospective Chronic Renal Insufficiency Cohort Study without proteinuria at study entry. Non-proteinuric CKD was defined as urine protein &lt;0.5g/day. We excluded subjects with heart failure or not on hypertension treatment. We used Cox proportional hazards regression to evaluate the association of RAS blockade vs. other antihypertensive therapy with CVD outcomes and death. The primary outcome was a composite of physician-adjudicated CVD events, including MI, stroke, heart failure hospitalization and death. Baseline covariates were adjusted through inverse probability of treatment weighting including: age, sex, race, education, smoking, BMI, diabetes, blood pressure, eGFR, and statin use. Results: A total of 2,825 of subjects met inclusion criteria. There were 2,068 subjects using vs 757 not using (73% vs 27%) RAS blockade at entry. Users had a similar age (61 vs 62 years) and eGFR (50 vs 51ml/min/1.73m 2 ) to non-users. Users were more likely to be male (66% vs 46%), to have diabetes (59% vs 30%), and to be on a statin (61% vs 50%). No significant association was found between RAS blockade and CVD events (adjusted HR 0.90, 95% CI 0.76-1.07) or mortality (adjusted HR 0.84, 95% CI 0.68-1.04) compared to other antihypertensive therapy. Conclusions: Among adults with non-proteinuric CKD, baseline use of RAS blockade was not associated with a lower risk of long-term events or mortality. Further studies are needed to determine if RAS blockade may play a role in high-risk patients with non-proteinuric CKD.

Calcium channel blockers for hypertension: old, but still useful

Calcium channel blockers (CCBs) constitute a heterogeneous class of drugs that can be divided into dihydropyridines (DHPs) and non-DHPs. DHP-CCBs are subcategorized into four generations based on the duration of activity and pharmacokinetics, while non-DHP-CCBs are subcategorized into phenylethylamine and benzodiazepine derivatives. DHP-CCBs are vascular-selective and function as potent vasodilators, whereas non-DHP-CCBs are cardiac-selective and are useful for treating tachyarrhythmia, but reduce cardiac contractility and heart rate. Traditional DHP-CCBs (nifedipine) mainly block L-type calcium channels, whereas novel CCBs block N-type (amlodipine) and/or T-type channels (efonidipine) in addition to L-type channels, leading to organ-protective effects. DHP-CCBs have a potent blood pressure–lowering effect and suppress atherosclerosis and coronary vasospasm. Diltiazem, a non-DHP-CCB, is highly effective for vasospasm control. CCBs reduce left ventricular hypertrophy and arterial stiffness. Amlodipine, a DHP-CCB, reduces blood pressure variability. L/N- and L/T-type CCBs combined with renin-angiotensin system blockers reduce proteinuria and improve kidney function compared with L-type CCBs. According to large-scale trials, DHP-CCBs reduce cardiovascular events in patients with isolated systolic hypertension, as well as in elderly and high-risk patients. Accordingly, CCBs are indicated for hypertension in elderly patients, isolated systolic hypertension, angina pectoris, and coronary vasospasm. Non-DHP-CCBs are contraindicated in high-grade heart block, bradycardia (&lt;60 beats per minute [bpm]), and heart failure with reduced ejection fraction (HFrEF). DHP-CCBs should be used with caution in patients with tachyarrhythmia, HFrEF, and severe leg edema, and non-DHP-CCBs should be used carefully in those with constipation. Each CCB has distinct pharmacokinetics and side effects, underscoring the need for meticulous consideration in clinical practice.

THU340 Efficacy And Safety Of Low-dose Spironolactone On Chronic Kidney Disease In Adults With Type 2 Diabetes: A Multicenter, Randomized Clinical Trial

Abstract Disclosure: A. Oiwa: None. D. Hiwatashi: None. T. Takeda: None. T. Miyamoto: None. I. Kawata: None. M. Koinuma: None. S. Kubota: None. S. Takayama: None. M. Yamazaki: None. M. Komatsu: None. Objective: To evaluate the albuminuria-lowering effect and safety regarding hyperkalemia of adding low-dose spironolactone (12.5 mg/day) to the renin-angiotensin system (RAS) blockers in adults with chronic kidney disease and type 2 diabetes. Research Design and Methods: This was a multicenter, open-label, randomized controlled trial. We enrolled 130 Japanese individuals aged ≥20 years with type 2 diabetes and albuminuria (≥30 mg/gCre), estimated glomerular filtration ≥30 mL/min/1.73 m2, and serum potassium level &amp;lt;5.0 mEq/L. They were randomly assigned to the spironolactone-administered and control groups. The main outcomes were changes in urine albumin-to-creatinine ratio (UACR), serum potassium levels and renal function from baseline to the 24-week interventional period. Results: The spironolactone-administered group showed a significant reduction in UACR by a mean of 103.47 ± 340.80 mg/gCre from baseline compared with the control group that showed increased UACR by a mean of 63.93 ± 310.14 mg/gCre (p = 0.0007, Wilcoxon rank-sum test and T-test). As for serum potassium levels, although there was a statistically significant increase (p = 0.0026), none of the participants had a potassium level ≥5.5 mEq/L at 24 weeks. Further, there was a tendency that the higher the initial potassium level, the smaller the increase in serum potassium level (estimate −0.37, analysis of covariance). Conclusions: This study first demonstrated that low-dose spironolactone administration reliably reduced albuminuria and was safe against hyperkalemia. The administration of spironolactone, which is the oldest known and most cost-effective of all the other mineralocorticoid receptor antagonists, should be re-evaluated with consideration of lower doses. Presentation: Thursday, June 15, 2023

Efficacy and safety of finerenone in chronic kidney disease and type 2 diabetes patients: a systematic review and meta-analysis.

The incidence of morbidity and mortality in patients with type 2 diabetes mellitus is substantially correlated with cardiovascular disease and chronic kidney disease. The current guidelines recommend the use of renin-angiotensin system blockers, but recent studies probed into the effects of finerenone to mitigate the risk of cardiorenal events. This meta-analysis was performed to demonstrate the effects of finerenone on cardiorenal events, comprising cardiovascular mortality, heart failure, change in estimated glomerular filtration rate, and serum potassium levels. After screening with our eligibility criteria, 350 articles were identified with an initial literature search on multiple databases, including PubMed, Science Direct, and Cochrane Central. Seven randomized controlled trials with a total of 15462 patients (n=8487 in the finerenone group; n=6975 in the control group) were included. Patients receiving finerenone were at a reduced risk for cardiovascular mortality [HR: 0.84 (0.74, 0.95)], heart failure [OR: 0.79 (0.68, 0.92)], decrease in estimated glomerular filtration rate by 40% [OR: 0.82 (0.74, 0.91)] and by 57% [OR: 0.70 (0.59, 0.82)]; and a higher incidence of moderate hyperkalemia [OR: 2.25 (1.78, 2.84)]. Finerenone, owing to its better mineralocorticoid affinity, and a much lower risk of adverse effects, promises to be a much better alternative than other renin-angiotensin system blockers available for the treatment of chronic kidney disease patients with type 2 diabetes. Further trials should be conducted to provide more definitive evidence to assess the safety and efficacy of finerenone compared to spironolactone and eplerenone.

Blood Pressure Variability as a Risk Factor for Cardiovascular Disease: Which Antihypertensive Agents Are More Effective?

Blood pressure oscillations during different time scales, known as blood pressure variability (BPV), have become a focus of growing scientific interest. BPV can be measured at long-term (seasonal variability or visit-to-visit), at mid-term (differences in consecutive days or weeks) or at short-term (day-night differences or changes induced by other daily activities and conditions). An increased BPV, either at long, mid or short-term is associated with a poor cardiovascular prognosis independently of the amount of blood pressure elevation. There is scarce evidence on the effect of different antihypertensive treatments on BPV, but some observational and interventional studies suggest that calcium channel blockers in general, and particularly amlodipine, either in monotherapy or combined with renin-angiotensin system blockers, can reduce BPV more efficiently than other antihypertensive drugs or combinations. Nevertheless, there are several aspects of the relationship between BPV, antihypertensive treatment, and clinical outcomes that are still unknown, and more work should be performed before considering BPV as a therapeutical target in clinical practice.