Angiotensin Receptor Blockers 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.

Angiotensin Receptor-Neprilysin Inhibition (Sacubitril/Valsartan) Reduces Structural Arterial Stiffness in Middle-Aged Mice.

Increasing arterial stiffness is a prominent feature of the aging cardiovascular system. Arterial stiffening leads to fundamental alterations in central hemodynamics with widespread detrimental implications for organ function resulting in significant morbidity and death, and specific therapies to address the underlying age-related structural arterial remodeling remain elusive. The present study investigates the potential of the recently clinically available dual angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan (LCZ696) to counteract age-related arterial fibrotic remodeling and stiffening in 1-year-old mice. Treatment of in 1-year-old mice with ARNI (sacubitril/valsartan), in contrast to angiotensin receptor blocker monotherapy (valsartan) and vehicle treatment (controls), significantly decreases structural aortic stiffness (as measured by invivo pulse-wave velocity and exvivo aortic pressure myography). This phenomenon appears, at least partly, independent of (indirect) blood pressure effects and may be related to a direct antifibrotic interference with aortic smooth muscle cell collagen production. Furthermore, we find aortic remodeling and destiffening due to ARNI treatment to be associated with improved parameters of cardiac diastolic function in aged mice. This study provides preclinical mechanistic evidence indicating that ARNI-based interventions may counteract age-related arterial stiffening and may therefore be further investigated as a promising strategy to improve cardiovascular outcomes in the elderly.

Sacubitril-Valsartan (LCZ696) in the Treatment of Systemic Hypertension: An Updated Review of Neprilysin Inhibition Combined with Angiotensin II Receptor Blockade.

Sacubitril-valsartan (LCZ696) has been demonstrated to be a highly effective treatment for heart failure with preserved ejection fraction since its Food and Drug Administration approval in 2015, and a growing body of evidence suggests its emergence as a hypertensive medication. It acts as an inhibitor of both neprilysin and the renin-angiotensin-aldosterone system, approaching the control of a multi-faceted pathology in multiple unique ways. Because 48% of US adults are affected by hypertension, with less than half of patients achieving controlled blood pressure, and the high correlation between uncontrolled hypertension and cardiovascular mortality, it is crucial to investigate new pharmacotherapies for managing this disease. This review discusses the current evidence of sacubitril-valsartan trials in hypertension management, with a focus on distinct populations and hypertension subsets. Asian populations are predisposed to salt-sensitive hypertension and have been shown to benefit from sacubitril-valsartan more than olmesartan, an angiotensin receptor blocker (ARB). Systolic hypertension from stiff, aging arteries commonly affects individuals over the age of 65 years, and responds demonstrably better to sacubitril-valsartan than ARB monotherapy. Patients with treatment-resistant hypertension, especially those with heart failure, also show significantly improved blood pressure when treated with sacubitril-valsartan over ARBs. We conclude with a discussion of sacubitril-valsartan's potential role in managing noncardiac disease.

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.

Highlights of Cardiovascular Disease Prevention Studies Presented at the 2022 American Heart Association Scientific Sessions.

Summarize selected late-breaking science on cardiovascular (CV) disease prevention presented at the 2022 scientific session of the American Heart Association (AHA). The PROMINENT trial compared pemafibrate to a placebo in patients with type 2 diabetes mellitus (DM) and mild-to-moderate hypertriglyceridemia and high-density lipoprotein cholesterol (HDL-C)<40 mg/dL who were already on guideline-directed statin therapy. The RESPECT-EPA trial compared purified eicosapentaenoic acid (EPA) and statin therapy to statin therapy alone for secondary prevention of atherosclerotic CV disease (ASCVD). SPORT compared the efficacy of low-dose statin therapy with a placebo and six commonly used dietary supplements on lipid and inflammatory markers. Data from long-term follow-up of the FOURIER-OLE study was presented to evaluate the efficacy of very low low-density lipoprotein cholesterol (LDL-C) levels with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Patient-level meta-analyses evaluated the association of statin therapy with new-onset DM and worse glycemic control. PROMPT-LIPID evaluated if automated electronic alerts to physicians with guideline-based recommendations improved the management of hyperlipidemia in patients at very high risk. NOTIFY-1 trial evaluated if notifying physicians and patients about coronary artery calcium (CAC) scores in non-ECG gated computed tomography scans led to increased prescription of statin therapy for primary ASCVD prevention. The DCP trial compared hydrochlorothiazide and chlorthalidone for blood pressure control and CV outcomes in hypertension. The CRHCP study compared the effectiveness of a village doctor for hypertension management and CV outcomes in rural areas of China. The QUARTET USA trial compared the effectiveness and safety of 4 antihypertensive medications in ultra-low doses with angiotensin-receptor blocker monotherapy. The late-breaking science presented at the 2022 scientific session of the AHA paves the way for future pragmatic trials and provides meaningful information to guide management strategies in cardiovascular disease prevention.

Dual therapy with an angiotensin receptor blocker and a JAK1/2 inhibitor attenuates dialysate-induced angiogenesis and preserves peritoneal membrane structure and function in an experimental CKD rat model.

Peritoneal dialysis (PD) is limited by reduced efficacy over time. We previously showed that a Janus kinase 1/2 inhibitor (JAK1/2i) reduced inflammation, hypervascularity and fibrosis induced by 4.25% dextrose dialysate (4.25%D) intraperitoneally (IP) infused for 10 days in rats with normal kidney function. JAK/STAT signalling mediates inflammatory pathways, including angiotensin signalling. We now tested the effect of long-term JAK1/2i and/or an angiotensin receptor blocker (ARB) on peritoneal membrane (PM) in polycystic kidneys (PCK) rats infused with 4.25%D. Except for controls, all PCK rats had a tunnelled PD catheter: (1) no infusions; (2) 4.25%D; (3) 4.25%D + JAK1/2i (5 mg/kg); (4) 4.25%D +losartan (5 mg/kg); and (5) 4.25%D + losartan +JAK1/2i (5 mg/kg each) IP BID × 16 weeks (N = 5/group). PM VEGFR2 staining areas and submesothelial compact zone (SMCZ) width were morphometrically measured. Peritoneal equilibration testing measured peritoneal ultrafiltration (UF) by calculating dialysate glucose at time 0 and 90 min (D/D0 glucose). 4.25%D caused hypervascularity, SMCZ widening, fibrosis and UF functional decline in PCK rats. Angiogenesis was significantly attenuated by JAK1/2i ± ARB but not by ARB monotherapy. Both treatments reduced SMCZ area. UF was preserved consistently by dual therapy (p < 0.05) but with inconsistent responses by monotherapies. Long-term JAK1/2i ± ARB reduced angiogenesis and fibrosis, and the combination consistently maintained UF. In clinical practice, angiotensin inhibition has been advocated to maintain residual kidney function. Our study suggests that adding JAK1/2i to angiotensin inhibition may preserve PM structure and UF.

Beneficial effects of RAS blockers in prediabetics with a hypertension-An observational cohort study

Hypertensive patients have a high prevalence of prediabetes and type II Diabetes mellitus. As per International Diabetic Federation, it has been estimated that more than 470 million people will have prediabetes by 2030. Approximately 5-10% of prediabetes progresses to overt diabetes mellitus, with the same proportion converting back to normoglycemia. In patients who are on Renin-Angiotensin System [RAS] blockers either an Angiotensin converting enzyme inhibitor (ACEI) or an Angiotensin receptor blocker (ARB) would slow down the progress of prediabetic state to overt or frank diabetes mellitus. This was a prospective, observational cohort study and a total of 125 hypertensive patients with impaired glucose tolerance were included in the study who were either on ACE inhibitor or ARB monotherapy. An oral Glucose Tolerance Test (GTT) was done at baseline for screening prediabetic patients, then a periodical assessment of glycemic indices, (fasting blood sugar, 2 hr postprandial blood sugar, and glycosylated hemoglobin), lipid profile, and complication status during the study period were evaluated every 3 months for18months. At the end of 1½ years, for patients belonging to the age group 18-54 years the FBS, PPBS, and HbA1C levels decreased significantly when the RAS blocking drugs (ACEIs and ARBs) were used continuously for 1 year and then they got stabilized. The beneficial effect was seen more in the younger age group 18-54 years old patients. Male above 54 years and females above 49 were resistant to the beneficial effects. In hypertensive patients with impaired glucose tolerance, the blockade of RAS with either ACE inhibitor or ARB has a significant preventive effect on the progression of Type II DM. It may be concluded from the finding of the present study that younger hypertensive patients (18-54 years) of either sex if found to be pre-diabetic may be administered ACEI or ARB as suitable for them. The treatment should be continued vigorously for one year and then it may be maintained to continue the beneficial effect.

Dyskalemia risk associated with fixed-dose anti-hypertensive medication combinations.

A model-based meta-analysis quantified comparative dyskalemia risk (hyper- or hypo-kalemia) in hypertensive patients treated with angiotensin receptor blockers (ARBs), a calcium channel blocker (CCB) and/or a thiazide diuretic (hydrochlorothiazide; HCTZ) as monotherapy or as fixed-dose combinations. Among 15 randomized controlled trials in a US Food and Drug Administration regulatory review database, dyskalemia events were reported by five trials (24 treatment arms, 11,030 subjects, 8-week median follow up time). The five trials evaluated monotherapy (ARB or HCTZ) alongside dual (ARB + HCTZ, ARB + CCB, or HCTZ + CCB) or triple fixed-dose combinations (ARB + CCB + HCTZ). Hypo- and hyper-kalemia rates were analyzed jointly to account for correlation. Significant drug class, drug, or dose effects were included in the final model. Effect on various drug- and dose combinations on dyskalemia risk were simulated and compared with model-estimated placebo arm dyskalemia risk. After a typical follow-up of 8 weeks, fixed-dose combinations of ARB with a high dose (25 mg) of HCTZ were associated with a higher hypokalemia risk difference (RD) from placebo (e.g.,Valsartan + HCTZ: 2.52%[95%CIs:1.17, 4.38%]). However, when ARB was combined with a lower, 12.5 mg dose of HCTZ, hypokalemia RD from placebo was not significant (Valsartan + HCTZ: -0.03%[-0.80, 0.71%]). ARB monotherapy raised hyperkalemia RD from placebo (1.3%[0.3, 3.6%]). Hyperkalemia risk was not appreciably higher than placebo for any FDC that combined ARB with HCTZ (Valsartan + HCTZ: 0.06%[-1.48, 1.64%]). In uncomplicated hypertensive patients, ARB + 12.5 mg HCTZ fixed-dose combinations are safer with respect to dyskalemia than either ARB or HCTZ monotherapy for initial antihypertensive treatment.

Efficacy of ARB/HCTZ Combination Therapy in Uncontrolled Hypertensive Patients Compared with ARB Monotherapy: A Meta-Analysis.

Objective To evaluate the efficacy of combination of angiotensin receptor blocker (ARB) with hydrochlorothiazide (HCTZ) compared to ARB alone in patients with uncontrolled hypertension via a systematic review and meta-analysis. Methods We searched databases till July 2019 using relevant search terms. We included articles that were randomised controlled trials (RCTs) comparing ARB/HCTZ with ARB for a duration of at least 4 weeks and reported on the efficacy or safety. Meta-analyses for efficacy outcomes were performed. In addition, groups given different concentrations of HCTZ (12.5 and 25 mg) were analysed separately. Results Sixteen RCTs (12,055 participants) were included. Overall, ARB/HCTZ combination therapy (both 12.5 and 25 mg HCTZ combination) resulted in better sitting systolic and diastolic blood pressure control than ARB alone (mean difference (95% confidence interval (CI): −5.69 [−6.66, −4.73] for 12.5 mg and −9.10 [−11.78, −6.42] for 25 mg and mean difference (95% CI): −2.91 [−3.31, −2.51] for 12.5 mg and −4.16 [−4.75, −3.58] for 25 mg). ARB/HCTZ combination therapy resulted in a higher rate of target blood pressure achievement compared to ARB alone (risk ratio (95% CI): 1.50 [1.42, 1.59]). ARB/HCTZ combination therapy had similar rates of total adverse events (AEs) and severe AEs compared to ARB alone. Conclusion ARB/HCTZ combination therapy is more efficacious for controlling blood pressure, and combination with a low concentration of HCTZ has similar AEs compared to ARB alone. Clinicians should consider adding HCTZ in the medication regime of patients with uncontrolled hypertension using ARB, if their clinical profile allows.

Renin–angiotensin system blockers and susceptibility to COVID-19: an international, open science, cohort analysis

SummaryBackgroundAngiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been postulated to affect susceptibility to COVID-19. Observational studies so far have lacked rigorous ascertainment adjustment and international generalisability. We aimed to determine whether use of ACEIs or ARBs is associated with an increased susceptibility to COVID-19 in patients with hypertension.MethodsIn this international, open science, cohort analysis, we used electronic health records from Spain (Information Systems for Research in Primary Care [SIDIAP]) and the USA (Columbia University Irving Medical Center data warehouse [CUIMC] and Department of Veterans Affairs Observational Medical Outcomes Partnership [VA-OMOP]) to identify patients aged 18 years or older with at least one prescription for ACEIs and ARBs (target cohort) or calcium channel blockers (CCBs) and thiazide or thiazide-like diuretics (THZs; comparator cohort) between Nov 1, 2019, and Jan 31, 2020. Users were defined separately as receiving either monotherapy with these four drug classes, or monotherapy or combination therapy (combination use) with other antihypertensive medications. We assessed four outcomes: COVID-19 diagnosis; hospital admission with COVID-19; hospital admission with pneumonia; and hospital admission with pneumonia, acute respiratory distress syndrome, acute kidney injury, or sepsis. We built large-scale propensity score methods derived through a data-driven approach and negative control experiments across ten pairwise comparisons, with results meta-analysed to generate 1280 study effects. For each study effect, we did negative control outcome experiments using a possible 123 controls identified through a data-rich algorithm. This process used a set of predefined baseline patient characteristics to provide the most accurate prediction of treatment and balance among patient cohorts across characteristics. The study is registered with the EU Post-Authorisation Studies register, EUPAS35296.FindingsAmong 1 355 349 antihypertensive users (363 785 ACEI or ARB monotherapy users, 248 915 CCB or THZ monotherapy users, 711 799 ACEI or ARB combination users, and 473 076 CCB or THZ combination users) included in analyses, no association was observed between COVID-19 diagnosis and exposure to ACEI or ARB monotherapy versus CCB or THZ monotherapy (calibrated hazard ratio [HR] 0·98, 95% CI 0·84–1·14) or combination use exposure (1·01, 0·90–1·15). ACEIs alone similarly showed no relative risk difference when compared with CCB or THZ monotherapy (HR 0·91, 95% CI 0·68–1·21; with heterogeneity of >40%) or combination use (0·95, 0·83–1·07). Directly comparing ACEIs with ARBs demonstrated a moderately lower risk with ACEIs, which was significant with combination use (HR 0·88, 95% CI 0·79–0·99) and non-significant for monotherapy (0·85, 0·69–1·05). We observed no significant difference between drug classes for risk of hospital admission with COVID-19, hospital admission with pneumonia, or hospital admission with pneumonia, acute respiratory distress syndrome, acute kidney injury, or sepsis across all comparisons.InterpretationNo clinically significant increased risk of COVID-19 diagnosis or hospital admission-related outcomes associated with ACEI or ARB use was observed, suggesting users should not discontinue or change their treatment to decrease their risk of COVID-19.FundingWellcome Trust, UK National Institute for Health Research, US National Institutes of Health, US Department of Veterans Affairs, Janssen Research & Development, IQVIA, South Korean Ministry of Health and Welfare Republic, Australian National Health and Medical Research Council, and European Health Data and Evidence Network.

Renin–angiotensin system inhibitors and COVID-19: overwhelming evidence against an association

Renin–angiotensin system inhibitors and COVID-19: overwhelming evidence against an association

Hypertension, renin–angiotensin–aldosterone system inhibition, and COVID-19

Hypertension, renin–angiotensin–aldosterone system inhibition, and COVID-19

Effect of angiotensin receptor blockers on blood pressure and renal function in patients with concomitant hypertension and chronic kidney disease: a systematic review and meta-analysis

Objective: Angiotensin receptor blockers (ARB) are among the recommended first-line treatment options in patients with hypertension and chronic kidney disease (CKD). This meta-analysis evaluated the effect of ARB on blood pressure (BP) and renal function in patients with concomitant hypertension and CKD with or without diabetes.Methods: Literature search was performed in PubMed/MEDLINE, EMBASE and BIOSIS to identify parallel-group, randomized controlled trials (≥8 weeks) reporting the effects of ARB on office systolic/diastolic BP (SBP/DBP), estimated glomerular filtration rate (eGFR), serum creatinine (SCr), creatinine clearance (CrCl) or proteinuria in adults with hypertension and CKD. Mean difference (MD, generic inverse variance) with 95% confidence intervals (CIs) was used to report an outcome.Results: Among the 24 studies identified, 19 evaluated ARB as monotherapy, 4 evaluated ARB as combination therapy and one evaluated ARB both as monotherapy and combination therapy. Median (range) duration of the studies was 12 (1.84–54.0) months. ARB monotherapy significantly (p < 0.01) reduced BP (treatment ≥1 year: SBP [MD: −14.84 mmHg; 95% CI: −17.82 to −11.85]/DBP [−10.27 mmHg; −12.26 to −8.27]) and proteinuria (≥1 year [−0.90 g/L; −1.22 to −0.59]). Results were consistent for combination therapy. In these studies, non-significant changes were observed for eGFR, CrCl and SCr. The impact of SBP changes on eGFR was not significant; however, studies were of a relatively short duration.Conclusion: ARB had a favorable impact on BP and renal parameters such as proteinuria with monotherapy as well as with combination therapy, highlighting their potential benefits in patients with hypertension and CKD. During the short follow-up of these studies, no significant change in eGFR was observed.

Angiotensin-converting enzyme inhibitors or angiotensin receptor blocker monotherapy retard deterioration of renal function in Taiwanese chronic kidney disease population

It remains unclear how different uses of angiotensin-converting inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) influence the progression of chronic kidney disease (CKD). This study explored CKD progression in a multicentre, longitudinal cohort study that included 2639 patients with CKD stage 1–5 and hypertension. Patients treated with ACEI or ARB for ≥90 days during a 6-mo period comprised the study group, or no treatment, comprised the control group. The study group was subdivided on the basis of treatment: ACEI monotherapy or ARB monotherapy. Progression of renal deterioration was defined by an average eGFR decline of more than 5 mL/min/1.73 m2/yr or the commencement of dialysis. With at least 1-year follow up, a progression of renal deterioration was demonstrated in 29.70% of the control group and 25.09% of the study group. Patients in the study group had significantly reduced progression of CKD with adjusted odds ratio 0.79 (95% confidence interval: 0.63–0.99). However, when ACEI monotherapy and ARB monotherapy were analyzed separately, none of their associations with CKD progression was statistically significant. In conclusion, ACEI or ARB monotherapy may retard the deterioration of renal function among patients with CKD and hypertension.

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.

Correction: Aliskiren therapy in hypertension and cardiovascular disease: a systematic review and a meta-analysis.

[This corrects the article DOI: 10.18632/oncotarget.19382.].

Aliskiren therapy in hypertension and cardiovascular disease: a systematic review and a meta-analysis.

The efficacy and safety of aliskiren combination therapy with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in patients with hypertension and cardiovascular disease remains attractive attention. We searched the Cochrane Central Register, the Clinical Trials Registry, EMBASE, MEDLINE and PubMed for relevant literatures up to January 2017. A total of 13 randomized controlled trials (RCTs) with 12222 patients were included in this study, and the combined results indicated that aliskiren in combination therapy with ACEIs or ARBs had remarkable effects in reducing systolic blood pressure (SBP) [weighted mean differences (WMD), -4.20; 95% confidential intervals (CI) -5.44 to -2.97; I2, 29.7%] and diastolic blood pressure (DBP: WMD, -2.09; 95% CI -2.90 to -1.27; I2, 0%) when compared with ACEIs or ARBs monotherapy, but with significantly increased the risk of hyperkalaemia [relative risk (RR), 1.45; 95% CI 1.28 to 1.64; I2,10.6 %] and kidney injury ( RR, 1.92; 95% CI 1.14 to 3.21; I2, 0%). Besides, there was no significant difference in the incidence of major cardiovascular events (RR, 0.95; 95% CI 0.89 to 1.02; I2, 0%) between the combined therapy and ACEIs or ARBs monotherapy. In conclusion, this meta-analysis demonstrated that aliskiren in combination therapy with ACEs/ARBs could control BP effectively, but is associated with increasing risks of hyperkalaemia and kidney injury, and have no benefit in preventing of major cardiovascular events.

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;