Angiotensin-converting Enzyme Inhibitor Monotherapy Research Articles

Angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers for preventing the progression of diabetic kidney disease.

Angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers for preventing the progression of diabetic kidney disease.

The Potential Role of Angiotensin-Converting Enzyme Inhibitors and Beta-Blockers in Reducing Pneumonia Severity in Older Adults.

Background Understanding the impact of pharmacological therapy on pneumonia severity is crucial for effective clinical management. The impact of angiotensin-converting enzyme inhibitors (ACEis) and beta-blockers (BBs) on pneumonia severity remains unknown, warranting further investigation. Methodology This retrospective study examined the hospital records of inpatients (≥75 years) admitted with community-acquired pneumonia in 2021. Pneumonia severity associated with the use of pre-established ACEi and BB therapy was documented using CURB-65 (confusion, uraemia, respiratory rate, blood pressure, age ≥65 years) and pneumonia severity index (PSI) scores. Descriptive statistics and multivariable linear regression were used to analyse differences across BB therapy, ACEi therapy, their combination, or neither (control group). Results A total of 803 patient records were examined, of whom 382 (47.6%) were male and 421 (52.4%) were female. Sample sizes for each group were as follows: control (n = 492), BB only (n = 185), ACEi only (n = 68), and BB + ACEi (n = 58). Distribution of aspiration pneumonia (AP) versus non-AP for each group, respectively, was control (21.1% vs. 78.9%), BB only (9.7% vs. 90.3%), ACEi only (7.3% vs. 92.7%), and ACEi + BB (12.1% vs. 87.9%). No significant differences in PSI and CURB-65 scores were found between intervention groups even after controlling for patient characteristics and irrespective of AP or non-AP aetiology. Patients with AP had significantly higher CURB-65 (p = 0.026) and PSI scores (p = 0.044) compared to those with non-AP. Conclusions Pre-prescribed ACEi or BB therapy did not appear to be associated with differences in pneumonia severity. There were no differences in pneumonia severity scores with ACEi and BB monotherapy or combined ACEi and BB therapy.

The association between dual RAAS inhibition and risk of acute kidney injury and hyperkalemia in patients with diabetic kidney disease: a systematic review and meta-analysis.

Dual renin-angiotensin-aldosterone system (RAAS) blockade involves dual therapy with a combination of angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), direct renin inhibitors (DRIs) or mineralocorticoid receptor antagonists (MRAs). It is hypothesized that dual RAAS blockade would result in a more complete inhibition of the RAAS cascade. However, large clinical trials on dual RAAS inhibition have shown increased risk of acute kidney injury (AKI) and hyperkalemia without additional benefit on mortality, cardiovascular events, or CKD progression compared to RAAS inhibitor monotherapy in patients with diabetic kidney disease (DKD). The development of newer, more selective non-steroidal MRAs as cardiorenal protective therapies has created a new opportunity for dual RAAS inhibition. We conducted a systematic review and meta-analysis of the risks of AKI and hyperkalemia with dual RAAS blockade in patients with DKD. This is a systematic review and meta-analysis of the randomized controlled trials (RCT) published from 2006 to May 30, 2022. Study population included adult patients with DKD receiving dual RAAS blockade. A total of 31 RCTs and 33048 patients were included in the systematic review. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random effects. There were 208 AKI events in 2690 patients on ACEi+ARB versus 170 in 4264 patients with ACEi or ARB monotherapy (pooled RR 1.48, 95% CI: 1.23-1.39). There were 304 hyperkalemia events in 2818 patients on ACEi+ARB versus 208 in 4396 patients with ACEi or ARB monotherapy (pooled RR 1.97, 95% CI: 1.32-2.94). A non-steroidal MRA+ACEi or ARB showed no increase in the risk of AKI (pooled RR 0.97, 95% CI: 0.81-1.16) compared to ACEi or ARB monotherapy but had a 2-fold higher risk of hyperkalemia with 953 events in 7837 patients in dual therapy versus 454 events in 6895 patients in monotherapy (pooled RR 2.05, 95% CI: 1.84-2.28). A steroidal MRA+ACEi or ARB had a 5-fold higher risk of hyperkalemia with 28 events in 245 at risk in dual therapy versus 5 events in 248 at risk in monotherapy (pooled RR 5.42 95% CI: 2.15-13.67). Dual therapy with RAASi is associated with an increased risk of AKI and hyperkalemia compared to RAASi monotherapy. Conversely, dual therapy with RAAS inhibitors and non-steroidal MRAs have no additional risk of AKI but a similar risk of hyperkalemia, which is lower than dual therapy with RAAS inhibitors and steroidal MRAs.

Clinical outcomes of renin angiotensin system inhibitor-based dual antihypertensive regimens in chronic kidney disease: a network meta-analysis

This study comprehensively investigated clinical outcomes associated with renin angiotensin system inhibitor-based dual antihypertensive regimens in non-dialysis chronic kidney disease (CKD) patients. Keyword searches of databases were performed per PRISMA-NMA guidelines. Frequentist network meta-analysis were conducted with 16 head-to-head randomized controlled trials. The effect sizes of dichotomous and continuous variables were estimated with odds ratio (OR) and standard mean differences (SMD), respectively. The protocol is registered in PROSPERO (CRD42022365927). Dual antihypertensive regimens with combination of angiotensin receptor blockers (ARB) and calcium channel blockers (CCB) demonstrated substantially reduced odd of major cardiovascular disease (CVD) events over other regimens including angiotensin converting enzyme inhibitor (ACEI) monotherapy (OR 3.19) and ARB monotherapy (OR 2.64). Most significant reductions in systolic (SBP) and diastolic blood pressure (DBP) were observed with ARB-based CCB dual regimen over ACEI monotherapy (SMD 17.60 SBP and 9.40 for DBP), ACEI-based CCB regimen (SMD 12.90 for SBP and 9.90 for DBP), and ARB monotherapy (SMD 13.20 for SBP and 5.00 for DBP). However, insignificant differences were noticed for the odds of hyperkalemia, end stage renal disease progression, and all-cause mortality. ARB-based CCB regimen has the greatest benefits on BP reduction as well as major CVD risks in non-dialysis CKD patients.

The Comparative Effectiveness of Monotherapy and Combination Therapies: Impact of Angiotensin Receptor Blockers on the Onset of Alzheimer's Disease.

The criteria for use of Alzheimer's disease (AD) drug Leqembi recommended by the Department of Veterans Affairs (VA) include patients aged 65 years or older with mild cognitive impairment (MCI) or mild AD. Comorbidities that include hypertension, hyperlipidemia, and diabetes are common among these patients. Our objective is to investigate the comparative effectiveness of the administration of one, two, or three medications belonging to the categories of angiotensin receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), Beta Blockers, Statins, and Metformin, for their potential to delay the clinical onset of AD and provide a window of opportunity for therapeutic intervention. Retrospective matched case-control study. Data from the Department of Veterans Affairs national corporate data warehouse. We conducted an analysis of 122,351 participants (13,611 with AD and 108,740 without AD), aged 65-89, who began at least one of the prescribed medication classes under investigation between October 1998 and April 2018. We utilized Cox proportional hazard regressions, both with and without propensity score weighting, to estimate hazard ratios (HR) associated with the use of different medication combinations for the pre-symptomatic survival time of AD onset. Additionally, we employed a supervised machine learning algorithm (random forest) to assess the relative importance of various therapies in predicting the occurrence of AD. Adding Metformin to the combination of ACEI+Beta Blocker (HR = 0.56, 95% CI (0.41, 0.77)) reduced the risk of AD onset compared to ACEI monotherapy alone (HR = 0.91, (0.85, 0.98)), Beta Blocker monotherapy (HR = 0.86, 95% CI (0.80, 0.92)), or combined ACEI+Beta Blocker (HR=0.85, 95%CI (0.77, 0.94)), when statin prescribers were used as a reference. Prescriptions of ARB alone or the combination of ARB with Beta Blocker showed an association with a lower risk of AD onset. Selected medications for the treatment of multiple chronic conditions among elderly individuals with hypertension, hyperlipidemia, and diabetes as monotherapy or combination therapies lengthen the pre-symptomatic period before the onset of AD.

Abstract P108: Side Effects Of Initial Combination Versus Monotherapy For Patients With Hypertension

Clinical guidelines recommend initiating combination antihypertensive therapy for many patients with hypertension. However, data on the risk of side effects are limited. We evaluated side effects associated with initiating combination therapy versus monotherapy among patients with hypertension from Kaiser Permanente Southern California between 2008-2014. Patient characteristics, antihypertensive medication use, and possible side effects were collected using electronic health records. We examined the association of initial combination therapy and incidence of side effects including acute kidney injury, hypotension, injurious fall, hyperkalemia, hypokalemia, hyponatremia, or hyperuricemia using multivariable Cox Proportional hazards models. Of 164,805 patients, 44% initiated combination therapy (34% angiotensin converting enzyme inhibitor (ACEI)-thiazide diuretics (TD); 10% other combinations) and 56% initiated monotherapy (22% ACEIs; 16% TD; 11% beta blockers (BB); 7% calcium channel blockers). Incidence rates of side effects were between 3.8 for hyperkalemia to 55.5 for hypokalemia per 1000 person-yrs during median follow-up of 0.27-0.45 yrs. Initiation of ACEI-TD combination therapy was associated with a lower risk of hyperkalemia than ACEI monotherapy and a lower risk of hypokalemia than TD monotherapy ( Table ). Initiation of ACEI-TD combination therapy was associated with a higher risk of hyponatremia, hyperuricemia, and hypotension, but not associated with injurious falls when compared with other monotherapy groups. Monitoring for side effects following initiation of antihypertensive medication with combination therapy may be useful.

A word on netting of angiotensin-converting enzyme inhibitor therapy in hypoplastic left heart syndrome following stage-I.

NPC-QIC Registry data showed that angiotensin-converting enzyme inhibitors were described in almost 38% for patients with single ventricle physiology after stage-I Norwood palliation. However, mortality and ventricular dysfunction or atrioventricular valve insufficiency seems to be not improved by oral application of angiotensin-converting enzyme inhibitors. The final conclusion was that despite limited evidence of benefit for patients with hypoplastic left heart syndrome, prescription of angiotensin-converting enzyme inhibitors during interstage is still common. Taking into account of the predominant cardiovascular regulation in newborns and young infants by circulating catecholamines, no real improvement is to be expected from angiotensin-converting enzyme inhibitor monotherapy. The goals of drug therapy after stage-I Norwood palliation in hypoplastic left heart syndrome are prevention of systemic right ventricle failure, balancing pulmonary and systemic blood flow, and reduction of oxygen consumption with regard to limitations of oxygen supply by the single ventricle, furthermore, avoiding harmful effects of endogenous catecholamine production in the long term on somatic and cognitive development. In this light of knowledge, we want to recommend the use of a long-acting and highly specific ß1-adrenoreceptor blocker for almost all patients after stage-I Norwood palliation and a combination with angiotensin-converting enzyme inhibitors only by indication after exclusion of potential side effects.

Organoprotective Effects of Spironolactone on Top of Ramipril Therapy in a Mouse Model for Alport Syndrome.

Angiotensin-converting enzyme inhibitors (ACEi) delay progression of the inherited renal disease Alport syndrome. However, the effect of ACEis weakens gradually due to an “aldosterone escape”. Here, we investigate if an aldosterone antagonist can counteract loss of ACEi-efficacy. COL4A3−/− mice were treated with ramipril (ACEi), starting at 4.5 weeks of age, and spironolactone was added at 7 weeks of age. Lifespan until renal failure, as well as kidney function parameters, were investigated. Dual therapy decreased proteinuria levels compared to ACEi monotherapy. Matrix accumulation, as well as tubulointerstitial and glomerular scar-tissue formation, were significantly reduced compared to untreated mice and ACEi-monotherapy at 75 and 100 days. Lifespan in dual treated mice was extended compared to untreated mice. However, lifespan was not superior to ACEi monotherapy–despite improved urea-nitrogen levels in the dual therapy group. In conclusion, adding the aldosterone-antagonist spironolactone to ACEi therapy further improved kidney function and reduced proteinuria and fibrosis. However, survival was not improved further, possibly due to premature death from side effects of dual therapy such as hyperkalemia. Thus, dual therapy could offer an effective therapy option for Alport syndrome patients with progressive proteinuria. However, the risks of adverse events require close monitoring.

Cardiovascular Drug Therapy during Interstage After Hybrid Approach: A Single-Center Experience in 51 Newborns with Hypoplastic Left Heart.

BackgroundNewborns with hypoplastic left heart (HLH) are usually palliated with the Norwood procedure or a hybrid stage I procedure. Hybrid is our preferred approach. Given the critical relationship between stage I, interstage, and comprehensive stage II or advanced biventricular repair, we hypothesized that appropriate drug treatment is a significant therapeutic cornerstone, especially for the management of the high-risk interstage.MethodsWe report a single-center observational study addressing the cardiovascular effects of, in particular, oral β-blockers and the additional use of angiotensin-converting enzyme (ACE) and mineralocorticoid inhibitors.ResultsIn total, 51 newborns—30 with HLH syndrome (HLHS) and 21 with HLH complex (HLHC)—with a median bodyweight of 3.0 kg (range 1.9–4.4; nine with bodyweight ≤ 2500 g) underwent an uneventful “Giessen hybrid approach” using a newly approved duct stent. All patients were discharged home with a single, double or triple therapy consisting of ß-blockers, ACE and mineralocorticoid inhibitors; 90% of the patients received bisoprolol, 10% received propranolol, 72% received lisinopril, and 78% received spironolactone. Resting heart rate decreased from 138 bpm (range 112–172; n = 51) at admission to 123 bpm (range 99–139; n = 51) at discharge and 110 bpm before stage II/biventricular repair/heart transplantation (range 90–140; n = 37) accompanied by favorable bodyweight gain. No side effects were evident.ConclusionIn view of drug risk/benefit profiles, as well as the variable morphology and hemodynamics, the highly selective β1-adrenoceptor blocker bisoprolol is our preferred drug for treatment of HLHS/HLHC in the interstage. We avoid using ACE inhibitor monotherapy and exclude potential risks for coronary and cerebral perfusion pressure beforehand.

ACE Inhibitor Benefit to Kidney and Cardiovascular Outcomes for Patients with Non-Dialysis Chronic Kidney Disease Stages 3-5: A Network Meta-Analysis of Randomised Clinical Trials.

BackgroundThe advantages of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) in reducing risk of cardiovascular events (CVEs) and delaying end-stage kidney disease (ESKD) in patients with chronic kidney disease (CKD) is well-known. However, the efficacy and safety of these agents in non-dialysis CKD stages 3–5 patients are still a controversial issue.MethodsTwo investigators (Yaru Zhang and Dandan He) independently searched and identified relevant studies from MEDLINE (from 1950 to October 2018), EMBASE (from 1970 to October 2018), and the Cochrane Library database. Randomised clinical trials in non-dialysis CKD3–5 patients treated with renin-angiotensin system (RAS) inhibitors were included. We used standard criteria (Cochrane risk of bias tool) to assess the inherent risk of bias of trials. We calculated the odds ratio (OR) and 95% confidence interval (CI) for each outcome by random-effects model. A 2-sided p value < 0.05 was considered statistically significant, and all statistical analyses were performed using STATA, version 15.0. This network meta-analysis was undertaken by the frequency model.ResultsForty-four randomised clinical trials with 42,319 patients were included in our network meta-analysis. ACEIs monotherapy significantly decreased the odds of kidney events (OR 0.54, 95% CI 0.41–0.73), cardiovascular events (OR 0.73, 95% CI 0.64–0.84), cardiovascular death (OR 0.73, 95% CI 0.63–0.86) and all-cause death (OR 0.77, 95% CI 0.66–0.91) when compared to placebo. According to the cumulative ranking area (SUCRA), ACEI monotherapy had the highest probabilities of their protective effects on outcomes of kidney events (SUCRA 93.3%), cardiovascular events (SUCRA 77.2%), cardiovascular death (SUCRA 86%), and all-cause death (SUCRA 94.1%), even if there were no significant differences between ACEIs and other antihypertensive drugs, including calcium channel blockers (CCBs), β-blockers and diuretics on above outcomes except for kidney events. ARB monotherapy and combination therapy of an ACEI plus an ARB showed no more advantage than CCBs, β-blockers and diuretics in all primary outcomes. In the subgroup of non-dialysis diabetic kidney disease patients, no drugs, including ACEIs or ARBs, significantly lowered the odds of cardiovascular events and all-cause death. However, ACEIs were still better than other antihypertensive drugs including ARBs in all-cause death but not ARBs in cardiovascular events according to the SUCRA. Only ARBs had significant differences in preventing the occurrence of kidney events compared with placebo (OR 0.82, 95% CI 0.72–0.95). Both ACEI/ARB monotherapy and combination therapy had higher odds of hyperkalaemia. ACEIs had 3.81 times higher odds than CCBs (95% CI 1.58–9.20), ARBs had 2.08–5.10 times higher odds than placebo and CCBs and combination therapy of an ACEI and an ARB had 4.80–24.5 times higher odds than all other treatments. Compared with placebo, CCBs and β blockers, ACEI therapy significantly increased the odds of cough (OR 2.90, 95% CI 1.76–4.77; OR 8.21, 95% CI 3.13–21.54 and OR 1.80, 95% CI 1.08–3.00). There were no statistical differences in hypotension among all comparisons except ACEIs versus placebo.ConclusionsAlthough ACEIs increased the odds of hyperkalaemia, cough and hypotension, they were still superior to ARBs and other antihypertensive drugs and had the highest benefits for the prevention of kidney events, cardiovascular outcomes, cardiovascular death and all-cause mortality in non-dialysis CKD3–5 patients. In patients with advanced diabetic kidney disease, ACEIs were superior to ARBs in lowering risk of all-cause death but not in kidney events and cardiovascular events.Electronic supplementary materialThe online version of this article (10.1007/s40265-020-01290-3) contains supplementary material, which is available to authorized users.

P2643Antiproteinuric efficacy of ACE inhibitors, selective MRAs and ACE inhibitor/selective MRA combination therapy in diabetic hypertensives with microalbuminuria

Abstract Background There is increasing evidence suggesting use of Mineralocorticoid Receptor Antagonists (MRA) in combination with Angiotensin Converting Enzyme Inhibitors (ACEI) or Angiotensin Receptor Blockers (ARB) to have a protective effect on chronic kidney disease patients. Purpose The aim of our study was to compare the antiproteinuric efficacy of ACEI monotherapy, Selective MRA monotherapy and their combination in mildly hypertensive patients with type 2 diabetes mellitus (DM) and microalbuminuria. Methods Seventy five patients with established diagnosis of type 2 DM, mild hypertension (systolic BP 140–159 mmHg and/or diastolic BP 90–99 mmHg) and microalbuminuria (30–299mg/g) were randomly assigned to one of three groups of therapy; ramipril 10 mg monotherapy (25 patients), eplerenone 50 mg monotherapy (25 patients) and eplerenone/ramipril 50/10 mg combination therapy (25 patients).The duration of the study was 24 weeks. All patients had measurement of blood pressure, urinary albumin/creatinine ratio, renal function tests and serum K level at baseline and at the end of the study after 24 weeks. All patients were followed up monthly till the end of the study for detection of side effects and/or treatment failure. Results Both ramipril and eplerenone monotherapy significantly reduced microalbuminuria after 24 weeks nearly to the same extent (37% and 38% respectively) without significant difference between both groups (P=0.95). There was more significant reduction of microalbuminuria in the eplerenone/ramipril combination group (60%) compared with ramipril and eplerenone monotherapy groups (P=0.0001).All groups showed significant reduction of both systolic and diastolic BP with more significant reduction of systolic BP in combination group compared with monotherapy groups (P&lt;0.0001).There was insignificant elevation of serum potassium level among the three groups with slightly higher non significant incidence of sustained hyperkalemia in combination group (P=0.5). All groups showed insignificant changes in serum creatinine and estimated glomerular filtration rate. Conclusion Addition of eplerenone (selective MRA) to an ACE inhibitor may confer further antiproteinuric benefit with low risk of hyperkalemia compared with MRA or ACEI monotherapy. Acknowledgement/Funding None

Clinical and economic implications of therapeutic switching of angiotensin receptor blockers to angiotensin-converting enzyme inhibitors: a population-based study.

To evaluate the clinical and cost impact of switching angiotensin receptor blockers (ARBs) to angiotensin-converting enzyme inhibitors (ACEIs) in patients with hypertension. This study used the UK Clinical Practice Research Datalink, linking with the Hospital Episode Statistics (April 2006 to March 2012). Adults with hypertension (n = 470) were followed from the first ARB prescription date to the switching date (preswitching period); then from the switching date to the date when study ended, patient left the dataset or died (postswitching period). Patients were divided into ACEIs-combined (n = 369) and ACEIs-monotherapy (n = 101) groups by whether additional antihypertensive drugs were prescribed with ACEIs in the postswitching period. Proportion of days covered (PDC), clinical outcomes and costs were compared between the preswitching and postswitching periods using a multilevel regression. Overall, in the postswitching period, there was a significant increase in the proportion of nonadherence (PDC < 80%) (OR: 2.4; 95% CI: 1.6-3.7), but a significant reduction in mean SBP (mean difference: -2.3; 95 CI: -3.4 to 1.2 mmHg) and mean DBP (mean difference: -1.9; 95% CI: -2.6 to -1.2 mmHg). However, these results were only observed in the ACEIs-combined group. There was no postswitching significant difference in either the incidence of individual or composite hypertension-related complications (OR: 0.9; 95% CI: 0.4-2.0). There was a significant reduction in the overall annual medical cost per patient by £329 (95% CI: -534 to -205). Switching of ARBs to ACEIs monotherapy appeared to be clinically effective and a cost-saving strategy. The observed changes in the ACEIs-combined group are assumed to be related to factors other than the ARBs switching.

The Long-Term Impact of Renin-Angiotensin System (RAS) Inhibition on Cardiorenal Outcomes (LIRICO): A Randomized, Controlled Trial.

The comparative effectiveness of treatment with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or their combination in people with albuminuria and cardiovascular risk factors is unclear. In a multicenter, randomized, open label, blinded end point trial, we evaluated the effectiveness on cardiovascular events of ACE or ARB monotherapy or combination therapy, targeting BP<130/80 in patients with moderate or severe albuminuria and diabetes or other cardiovascular risk factors. End points included a primary composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for cardiovascular causes and a revised end point of all-cause mortality. Additional end points included ESRD, doubling of serum creatinine, albuminuria, eGFR, BP, and adverse events. Because of slow enrollment, the trial was modified and stopped 41% short of targeted enrollment of 2100 participants, corresponding to 35% power to detect a 25% reduced risk in the primary outcome. Our analysis included 1243 adults, with median follow-up of 2.7 years. Efficacy outcomes were similar between groups (ACE inhibitor versus ARB, ACE inhibitor versus combination, ARB versus combination) as were rates of serious adverse events. The rate of permanent discontinuation for ARB monotherapy (6.3%) was significantly lower than for ACE inhibitor monotherapy (15.7%) or combined therapy (18.3%). Patients may tolerate ARB monotherapy better than ACE inhibitor monotherapy. However, data from this trial and similar trials, although as yet inconclusive, show no trend suggesting differences in mortality and renal outcomes with ACE inhibitors or ARBs as dual or monotherapy in patients with albuminuria and diabetes or other cardiovascular risk factors.

A Review of ACE Inhibitors and ARBs in Black Patients With Hypertension.

To review current guidelines and recent data evaluating the efficacy and safety of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) in black hypertensive patients. Articles evaluating race-specific outcomes in hypertension were gathered using a MEDLINE search with keywords black, African American, ACE inhibitor, angiotensin receptor blocker, angiotensin system, and hypertension. Studies published from 2000 through April 2018 were reviewed. Six guidelines, 8 monotherapy publications, and 5 combination therapy publications included race-specific results and were included in the review. The authors individually compared and contrasted the results from each publication. Numerous monotherapy trials indicate that black patients may have a reduced blood pressure (BP) response with ACE inhibitors or ARBs compared with white patients. Conversely, additional studies propose that race may not be the primary predictor of BP response. Reduced efficacy is not observed in trials involving combination therapy. Some studies suggest increased cardiovascular and cerebrovascular morbidity and mortality with ACE inhibitor or ARB monotherapy in black patients; however, data are conflicting. Relevance to Patient Care and Clinical Practice: This article clarifies vague guideline statements and informs clinicians on the appropriate use of ACE inhibitors or ARBs for hypertension treatment in black patients through an in-depth look into the evidence. Potentially reduced efficacy and limited outcomes data indicate that ACE inhibitors or ARBs should not routinely be initiated as monotherapy in black hypertensive patients. Use in combination with a calcium channel blocker or thiazide diuretic is efficacious in black patients, and there are no data showing that this increases or decreases cardiovascular or cerebrovascular outcomes.

Integrated Treatment of Prostaglandin E1 and Angiotensin-Converting Enzyme Inhibitor in Diabetic Kidney Disease Rats: Possible Role of Antiapoptosis in Renal Tubular Epithelial Cells.

To investigate the therapeutic mechanisms underlying prostaglandin E1 (PGE1) and angiotensin-converting enzyme inhibitor (ACEI) on reducing urinary protein in diabetic kidney disease (DKD). DKD rats were established and randomly divided into four groups: PGE1 (10 μg/kg/day) (P group), ACEI (10 mg/kg/day) (A group), combination of PGE1 with ACEI treatment (P + A group), and saline treatment group (DKD group). Untreated rats were used as normal control (N group). Urinary albumin, endothelin-1 (ET-1), angiotensin II (AngII), TUNEL assay, Masson's trichrome staining, and immunohistochemistry staining for CD68 were evaluated in all groups. Ten days after treatment, urinary albumin was significantly decreased in the P and P + A groups (p < 0.01 vs. the DKD group). At the end of 8 weeks, the albumin was still significantly reduced in the P + A group (p < 0.05 vs. the A group). ET-1 and AngII were also significantly decreased in three treatment groups (p < 0.01 vs. the DKD group), especially in the P + A group. Few cells underwent apoptosis in glomerular regions in DKD rats, while amounts of apoptotic cells were seen in tubules regions. Further, apoptosis and the areas of fibrosis in tubulointerstitial were both decreased most in the P + A group compared with the DKD group. Apoptosis of renal tubular epithelial cells may participate in the development and progression of DKD in rats. Combination of PGE1 with AGEI remarkably protects renal function compared with PGE1 or ACEI monotherapy. The potential therapeutic mechanisms of PGE1 and AGEI might be via multiple targets and, at least in part, through inhibiting the apoptosis of renal tubular epithelial cells.

Pharmacological Monotherapy versus Renal Artery Denervation in Controlled Hypertensive Patients

&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;The aim of this prospective observational non-inferiority study was to compare the capacity for control of essential hypertension between renal sympathetic denervation (RSD) and either angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and results&lt;/strong&gt;: Seventy-four previously controlled essential hypertensive patients on ACEI/ARB monotherapy were evaluated; eleven patients agreed to proceed with RSD and had their antihypertensive agent withdrawn on the day of the procedure. During the six months of follow-up, there was no significant change in mean 24-hour ambulatory blood pressure measurements (ABPM) from baseline to three and sixmonths in the ACEI/ARB group (118±8/80±3 &lt;em&gt;vs.&lt;/em&gt; 116±8/79±3 and 115±8/79±4 mmHg, respectively). No change was also observed in the RSD group (117±8/81±2 &lt;em&gt;vs.&lt;/em&gt; 115±6/80±2 and 114±7/79±3 mmHg, respectively). There were no differences between groups at interval time points. There were also no changes in renal function or echocardiographic parameters, during follow-up.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; For the first time, this study reports possible non-inferiority of RSD when compared to ACEI or ARB monotherapy in the control of essential hypertension. A randomized trial with appropriate concealment of treatment, more patients and an extended follow-up period is needed to evaluate the potential benefits of RSD in comparison to ACEI/ARB use in patients with controlled hypertension.&lt;/p&gt;

Renoprotective Effect of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Diabetic Patients with Proteinuria

Background/Aims: Limited evidence exists on the choice of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in diabetic patients with nephropathy. We aim to assess the renal effectiveness and safety of these drugs among diabetic nephropathy patients. Methods: This retrospective cohort study was conducted with diabetic nephropathy patients who initiated ACEI or ARB monotherapy. The primary outcome was a composite of end stage of renal disease and renal transplantation, and the secondary outcome was all-cause mortality. The safety endpoint was hyperkalemia. Results: Three thousand seven hundred and thirty-nine ACEI users and 3,316 ARB users were identified. ARBs seemed to be inferior to ACEIs given their poorer renal outcome (HR 1.31; 95% CI, 1.15-1.50) and higher risk of hyperkalemia (HR 1.17; 95% CI, 1.04-1.32). Among the four ACEIs compared, captopril was an inferior treatment choice given its poorer renal outcomes (HR 1.42; 95% CI, 1.05-1.93) and higher mortality rate (HR 1.25; 95% CI, 1.01-1.55). Irbesartan appeared to be a poorer treatment choice among the three ARBs compared, given its inferior renal protective effect (HR 1.35; 95% CI, 1.03-1.78). Conclusions: Our findings suggest ACEIs as a relatively more renoprotective and safer treatment as compared to ARBs. Captopril and irbesartan may be inferior to the other ACEIs and ARBs respectively.

Thirty Years of Evidence on the Efficacy of Drug Treatments for Chronic Heart Failure With Reduced Ejection Fraction: A Network Meta-Analysis.

Treatments that reduce mortality and morbidity in patients with heart failure with reduced ejection fraction, including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), β-blockers (BB), mineralocorticoid receptor antagonists (MRA), and angiotensin receptor-neprilysin inhibitors (ARNI), have not been studied in a head-to-head fashion. This network meta-analysis aimed to compare the efficacy of these drugs and their combinations regarding all-cause mortality in patients with heart failure with reduced ejection fraction. A systematic literature review identified 57 randomized controlled trials published between 1987 and 2015, which were compared in terms of study and patient characteristics, baseline risk, outcome definitions, and the observed treatment effects. Despite differences identified in terms of study duration, New York Heart Association class, ejection fraction, and use of background digoxin, a network meta-analysis was considered feasible and all trials were analyzed simultaneously. The random-effects network meta-analysis suggested that the combination of ACEI+BB+MRA was associated with a 56% reduction in mortality versus placebo (hazard ratio 0.44, 95% credible interval 0.26-0.66); ARNI+BB+MRA was associated with the greatest reduction in all-cause mortality versus placebo (hazard ratio 0.37, 95% credible interval 0.19-0.65). A sensitivity analysis that did not account for background therapy suggested that ARNI monotherapy is more efficacious than ACEI or ARB monotherapy. The network meta-analysis showed that treatment with ACEI, ARB, BB, MRA, and ARNI and their combinations were better than the treatment with placebo in reducing all-cause mortality, with the exception of ARB monotherapy and ARB plus ACEI. The combination of ARNI+BB+MRA resulted in the greatest mortality reduction.

Combined use of renin-angiotensin-aldosterone system-acting agents: a cross-sectional study.

Background Due to recent EU warnings and restrictions on the combined use of renin-angiotensin-aldosterone system (RAAS)-acting agents, and the seriousness of the associated harm, we analyzed the prescription of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) as dual therapy or associated with spironolactone. Setting An administrative claims database of a regional hospital in Romania. Methods We retrospectively included all adult patients hospitalized during 18months in 2013-2014, discharged with a prescription of a RAAS-acting agent. Main outcome measures Counts of ACEIs and ARBs co-prescription, of ACEIs or ARBs combined with spironolactone, co-morbidities, co-medication, creatinine, and electrolytes assessment and values. Results Out of 1697 patients with a prescription of a RAAS-acting agent, 24 (1.4%) were co-prescribed ACEIs and ARBs, and 416 (24.5%) ACEIs or ARBs with spironolactone. Patients prescribed dual ACEI/ARB therapy and the ones with ACEI or ARB-spironolactone combination had significantly higher prevalence of increased creatinine level before discharge, compared to the ACEI and ARB monotherapy groups (48 and 31% compared to 17 and 27%). Subjects with diabetes, heart failure, ischaemic heart disease, or urea ≥40mg/dL had higher odds of having ACEI or ARB-spironolactone combination compared to monotherapy, while hypertension and renal disease subjects had lower odds. Similar findings were comparing dual ACEI/ARB therapy to monotherapy except heart failure (not statistically significant). Conclusion Overall, the prevalence of use of dual therapy was low. The combined use of RAAS-acting agents was higher in patients with known risk factors for further renal function deterioration, compared to the ones without.

Persistence and compliance with newly initiated antihypertensive drug treatment in patients with chronic kidney disease.

BackgroundPatients with chronic kidney disease initiating an antihypertensive drug (AH) treatment must persist and comply with it to slow disease progression and benefit from the reduction of cardiovascular morbidity and mortality.ObjectivesThis study evaluates the persistence and compliance with AH treatment and identifies the associated factors among chronic kidney disease patients who initiated AH treatment.MethodsA population-based cohort study using Quebec administrative data was conducted. Patients who still take any AH 1 year after initiation were considered persistent. Of these patients, those who had ≥80% of days covered with an AH in the year after initiation were considered compliant. Factors associated with persistence and compliance were identified using a modified Poisson regression.ResultsOf the 7,119 eligible patients, 78.8% were persistent, 87.7% of whom were compliant with their AH treatment. Compared with patients on diuretic monotherapy, those who initially used angiotensin-converting enzyme inhibitor monotherapy, angiotensin II receptor blocker monotherapy, calcium channel blocker monotherapy, β-blocker monotherapy, or multidrug therapy were more likely to be persistent. In contrast, individuals who visited their physicians ≥17 times were less likely to be persistent than those who visited between 0 and 8 times. The patients who were more likely to be compliant had initially used an angiotensin-converting enzyme inhibitor, β-blocker, calcium channel blocker, or multitherapy as opposed to a diuretic.ConclusionA year after initiating AH treatment, nearly a third of chronic kidney disease patients were either not taking an AH or had not been compliant. Factors associated with persistence and compliance could help identify patients who need help in managing their AH treatment.