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Journal of Clinical Hypertension... Mar 2013Many hypertensive patients require ≥2 drugs to achieve blood pressure targets. This study aims to review and analyze the clinical studies conducted with dual or triple... (Meta-Analysis)
Meta-Analysis Review
Many hypertensive patients require ≥2 drugs to achieve blood pressure targets. This study aims to review and analyze the clinical studies conducted with dual or triple combination of angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), and diuretics. Medical literature between January 1990 and April 2012 was reviewed systematically and data from eligible studies were abstracted. Data were analyzed using random-effects models. Of the 224 studies screened, 7563 eligible patients from 11 studies were included. Triple combinations of ARBs (olmesartan or valsartan), CCBs (amlodipine), and diuretics (hydrochlorothiazide) at any dose provided more blood pressure reduction in office and 24-hour ambulatory measurements than any dual combination of these molecules (P<.0001 for both). Significantly more patients achieved blood pressure targets with triple combinations (odds ratio, 2.16; P<.0001). Triple combinations did not increase adverse event risk (odds ratio, 0.96; P=.426). Triple combinations at any dose seem to decrease blood pressure more effectively than dual combination of the same molecules without any remarkable risk elevation for adverse events. Further prospective studies evaluating the efficacy and safety of triple combinations, especially in the form of single pills, are required.
Topics: Angiotensin Receptor Antagonists; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Diuretics; Drug Therapy, Combination; Humans; Hypertension; Treatment Outcome
PubMed: 23458592
DOI: 10.1111/jch.12040 -
International Journal of Molecular... Mar 2022Stroke is the primary cause of disability in the adult population. Hypertension represents the leading risk factor being present in almost half the patients. The... (Review)
Review
Stroke is the primary cause of disability in the adult population. Hypertension represents the leading risk factor being present in almost half the patients. The renin-angiotensin system is involved in the physiopathology of stroke and has an essential impact on hypertension as a risk factor. This article targeted the role of the renin-angiotensin system in stroke neuroprotection by reviewing the current literature available. The mechanism of action of the renin-angiotensin system was observed through the effects on AT1, AT2, and Mas receptors. The neuroprotective properties ascertained by angiotensin in stroke seem to be independent of the blood pressure reduction mechanism, and include neuroregeneration, angiogenesis, and increased neuronal resistance to hypoxia. The future relationship of stroke and the renin-angiotensin system is full of possibilities, as new agonist molecules emerge as potential candidates to restrict the impairment caused by stroke.
Topics: Humans; Hypertension; Neuroprotection; Renin-Angiotensin System; Stroke
PubMed: 35409237
DOI: 10.3390/ijms23073876 -
International Journal of Cardiology.... Dec 2020Animal studies suggested that angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARB) facilitate the inoculation of potentially leading...
OBJECTIVE
Animal studies suggested that angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARB) facilitate the inoculation of potentially leading to a higher risk of infection and/or disease severity. We aimed to systematically evaluate the risk of COVID-19 infection and the risk of severe COVID-19 disease associated with previous exposure to (ACEi) and/or ARB).
METHODS
MEDLINE, CENTRAL, PsycINFO, Web of Science Core Collection were searched in June 2020 for controlled studies. Eligible studies were included and random-effects meta-analyses were performed. The estimates were expressed as odds ratios (OR) and 95% confidence intervals (95%CI). Heterogeneity was assessed with I test. The confidence in the pooled evidence was appraised using the GRADE framework.
RESULTS
Twenty-seven studies were included in the review. ACEi/ARB exposure did not increase the risk of having a positive test for COVID-19 infection (OR 0.99, 95%CI 0.89-1.11; I = 36%; 5 studies, GRADE confidence moderate). The exposure to ACEi/ARB did not increase the risk of all-cause mortality among patients with COVID-19 (OR 0.91, 95%CI 0.74-1.11; I = 20%; 17 studies; GRADE confidence low) nor severe/critical COVID-19 disease (OR 0.90, 95%CI 0.74-1.11; I = 55%; 17 studies; GRADE confidence very low). Exploratory analyses in studies enrolling hypertensive patients showed a association of ACEi/ARB with a significant decrease of mortality risk.
CONCLUSIONS
ACEi/ARB exposure does not seem to increase the risk of having the SARS-CoV-2 infection or developing severe stages of the disease including mortality. The potential benefits observed in mortality of hypertensive patients reassure safety, but robust studies are required to increase the confidence in the results.
PubMed: 32875060
DOI: 10.1016/j.ijcha.2020.100627 -
ESC Heart Failure Nov 2017Studies with angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) in patients with heart failure with preserved ejection fraction... (Meta-Analysis)
Meta-Analysis Review
Studies with angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) in patients with heart failure with preserved ejection fraction (HFpEF) have yielded inconsistent results. To conduct a systematic review and meta-analysis of all evidence for ACE-I and ARBs in patients with HFpEF, we searched PubMed, Ovid SP, Embase, and Cochrane database to identify randomized trials and observational studies that compared ACE-I or ARBs against placebo or standard therapy in HFpEF patients. Random-effect models were used to pool the data, and I testing was performed to assess the heterogeneity of the included studies. A total of 13 studies (treatment arm = 8676 and control arm = 8608) were analysed. Pooled analysis of randomized trials for ACE-I and ARBs (n = 6) did not show any effect on all-cause mortality [relative risk (RR) = 1.02, 95% confidence interval (CI) = 0.93-1.11, P = 0.68, I = 0%], while results from observational studies showed a significant improvement (RR = 0.91, 95% CI = 0.87-0.95, P = 0.005, I = 81.5%). In pooled analyses of all studies, ACE-I showed a reduction of all-cause mortality (RR = 0.91, 95% CI = 0.87-0.95, P = 0.01). There was no reduction in cardiovascular mortality seen, but in pooled analysis of randomized trials, there was a trend towards reduced HF hospitalization risk (RR = 0.91, 95% CI = 0.83-1.01, I = 0%, P = 0.074). These data suggest that ACE-I and ARBs may have a role in improving outcomes of patients with HFpEF, underscoring the need for future research with careful patient selection, and trial design and conduct.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Heart Failure; Humans; Renin-Angiotensin System; Stroke Volume
PubMed: 28869332
DOI: 10.1002/ehf2.12204 -
European Heart Journal. Cardiovascular... Jan 2024Randomized controlled trials (RCTs) have assessed the effects of renin-angiotensin system (RAS) blockers in adults with coronavirus disease 2019 (COVID-19). This... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Randomized controlled trials (RCTs) have assessed the effects of renin-angiotensin system (RAS) blockers in adults with coronavirus disease 2019 (COVID-19). This meta-analysis provides estimates of the safety and efficacy of treatment with (vs. without) RAS blockers from these trials.
METHODS
PubMed, Web of Science, and ClinicalTrials.gov were searched (1 March-12 April 2023). Event/patient numbers were extracted, comparing angiotensin-converting enzyme (ACE) inhibitor/angiotensin-receptor blocker (ARB) treatment with no treatment, for the outcomes: intensive care unit (ICU) admission, mechanical ventilation, vasopressor use, acute kidney injury (AKI), renal replacement therapy (RRT), acute myocardial infarction, stroke/transient ischaemic attack, heart failure, thromboembolic events, and all-cause death. Fixed-effects meta-analysis estimates were pooled.
RESULTS
Sixteen RCTs including 3492 patients were analysed. Compared with discontinuation of RAS blockers, continuation was not associated with increased risk of ICU [risk ratio (RR) 0.96, 0.66-1.41], ventilation (RR 0.77, 0.55-1.09), vasopressors (RR 0.92, 0.58-1.44), AKI (RR 1.01, 0.40-2.56), RRT (RR 1.01, 0.46-2.21), or thromboembolic events (RR 1.07, 0.36-3.19). RAS blocker initiation was not associated with increased risk of ICU (RR 0.71, 0.47-1.08), ventilation (RR 1.12, 0.91-1.38), AKI (RR 1.28, 0.89-1.86), RRT (RR 1.66, 0.89-3.12), or thromboembolic events (RR 1.20, 0.06-23.70), although vasopressor use increased (RR 1.27, 1.02-1.57). The RR for all-cause death in the continuation/discontinuation trials was 1.24 (0.80-1.92), and 1.22 (0.96-1.55) in the initiation trials. In patients with severe/critical COVID-19, RAS blocker initiation increased the risk of all-cause death (RR 1.31, 1.01-1.72).
CONCLUSION
ACE inhibitors and ARBs may be continued in non-severe COVID-19 infection, where indicated. Conversely, initiation of RAS blockers may be harmful in critically ill patients.PROSPERO registration number: CRD42023408926.
Topics: Adult; Humans; Acute Kidney Injury; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; COVID-19; Randomized Controlled Trials as Topic; Renin-Angiotensin System
PubMed: 37740450
DOI: 10.1093/ehjcvp/pvad067 -
Annals of Internal Medicine Aug 2020The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in coronavirus disease 2019 (COVID-19) susceptibility, severity,...
BACKGROUND
The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in coronavirus disease 2019 (COVID-19) susceptibility, severity, and treatment is unclear.
PURPOSE
To evaluate, on an ongoing basis, whether use of ACEIs or ARBs either increases risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or is associated with worse COVID-19 disease outcomes, and to assess the efficacy of these medications for COVID-19 treatment.
DATA SOURCES
MEDLINE (Ovid) and Cochrane Database of Systematic Reviews from 2003 to 4 May 2020, with planned ongoing surveillance for 1 year; the World Health Organization database of COVID-19 publications and medRxiv.org through 17 April 2020; and ClinicalTrials.gov to 24 April 2020, with planned ongoing surveillance.
STUDY SELECTION
Observational studies and trials in adults that examined associations and effects of ACEIs or ARBs on risk for SARS-CoV-2 infection and COVID-19 disease severity and mortality.
DATA EXTRACTION
Single-reviewer abstraction confirmed by another reviewer, independent evaluation by 2 reviewers of study quality, and collective assessment of certainty of evidence.
DATA SYNTHESIS
Two retrospective cohort studies found that ACEI and ARB use was not associated with a higher likelihood of receiving a positive SARS-CoV-2 test result, and 1 case-control study found no association with COVID-19 illness in a large community (moderate-certainty evidence). Fourteen observational studies, involving a total of 23 565 adults with COVID-19, showed consistent evidence that neither medication was associated with more severe COVID-19 illness (high-certainty evidence). Four registered randomized trials plan to evaluate ACEIs and ARBs for treatment of COVID-19.
LIMITATION
Half the studies were small and did not adjust for important confounding variables.
CONCLUSION
High-certainty evidence suggests that ACEI or ARB use is not associated with more severe COVID-19 disease, and moderate-certainty evidence suggests no association between use of these medications and positive SARS-CoV-2 test results among symptomatic patients. Whether these medications increase the risk for mild or asymptomatic disease or are beneficial in COVID-19 treatment remains uncertain.
PRIMARY FUNDING SOURCE
None. (PROSPERO: registration number pending).
Topics: Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Betacoronavirus; COVID-19; Coronavirus Infections; Humans; Observational Studies as Topic; Pandemics; Pneumonia, Viral; Risk Factors; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 32422062
DOI: 10.7326/M20-1515 -
Journal of the... Sep 2011Candesartan is a relatively novel antihypertensive agent of the angiotensin receptor blocker (ARB). Several clinical trials have compared candesartan with losartan in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Candesartan is a relatively novel antihypertensive agent of the angiotensin receptor blocker (ARB). Several clinical trials have compared candesartan with losartan in the management of essential hypertension. However, systematic assessment of efficacy and safety between candesartan and losartan is still lacking.
METHODS
We reviewed randomised controlled trials (RCTs) comparing candesartan with losartan for net reduction in blood pressure from baseline, response and control rates, and incidences of common and serious adverse events.Weighted mean differences (WMD), and relative risk (RR) with 95% confidence intervals (CI) were calculated for continuous and dichotomous data, respectively.
RESULTS
A total of 12 RCTs with 3644 patients were included in this meta-analysis. When comparing the efficacy of candesartan and losartan in reducing systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the end of the follow-up period, results with candesartan were superior to losartan in the reduction SBP and DBP (WMD, -2.97; 95% CI, -4.18 - -1.77; p < 0.001; WMD, -1.76; 95% CI, -2.57 - -0.96; p < 0.001; respectively). Candesartan had better response and control rates than losartan. (RR, 1.12; 95% CI, 1.06-1.18; p < 0.01; RR, 1.26; 95% CI, 1.06-1.50; p = 0.008). Reported common adverse events for the two agents were not significantly different (RR, 0.98; 95% CI, 0.86-1.12; p = 0.78). The incidence of serious adverse events for candesartan was lower than for losartan (RR, 0.48; 95% CI, 0.25-0.92; p = 0.03). The net reduction of DBP showed negative correlation with baseline DBP in both candesartan and losartan groups (regression coefficient -1.81, p = 0.03 and regression coefficient -1.56, p = 0.02, respectively).
CONCLUSIONS
Candesartan is superior to losartan in reducing blood pressure. Candesartan also causes fewer serious adverse events than losartan.
Topics: Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Humans; Hypertension; Losartan; Publication Bias; Regression Analysis; Tetrazoles; Treatment Outcome
PubMed: 21421652
DOI: 10.1177/1470320310391503 -
ESC Heart Failure Feb 2024Guideline-directed medical therapy (GDMT) has improved outcomes in patients with heart failure, including the use of renin-angiotensin-aldosterone system inhibitors,... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of new potassium binders on renin-angiotensin-aldosterone system inhibitor optimization in heart failure patients: a systematic review and meta-analysis.
Guideline-directed medical therapy (GDMT) has improved outcomes in patients with heart failure, including the use of renin-angiotensin-aldosterone system inhibitors, which can hinder the excretion of potassium, resulting in hyperkalaemia. New potassium binders (NPBs) can prevent this adverse effect; however, the efficacy and safety of NPB for this indication have not been fully established. We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, Scopus, and Cochrane through 26 April 2023. The risk of bias assessment was conducted, following Cochrane's updated Risk of Bias 2 assessment tool. We used the fixed-effects model to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI) (PROSPERO ID: CRD42023426113). We included six RCTs with a total of 1432 patients. NPB was significantly associated with successful mineralocorticoid receptor antagonist (MRA) optimization [RR: 1.13 with 95% CI (1.02-1.25), P = 0.02], decreased patients with MRA at less than the target dose [RR: 0.72 with 95% CI (0.57-0.90), P = 0.004], and decreased hyperkalaemic episodes [RR: 0.42 with 95% CI (0.24-0.72), P = 0.002]. However, there was no difference between NPB and placebo regarding angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/angiotensin receptor/neprilysin inhibitor (ANRi) optimization [RR: 1.02 with 95% CI (0.89-1.17), P = 0.76] and serum potassium change [MD: -0.31 with 95% CI (-0.61 to 0.00), P = 0.05], with an acceptable safety profile except for the increased incidence of hypokalaemia with NPB [RR: 1.57 with 95% CI (1.12-2.21), P = 0.009]. NPB has been shown to improve GDMT outcomes by enhancing MRA optimization and reducing hyperkalaemic episodes. However, there are limited data on the effects of NPB on ACEi/ARB/ANRi optimization. Future RCTs should investigate ACEi/ARB/ANRi optimization and conduct head-to-head comparisons of NPB (patiromer and sodium zirconium cyclosilicate).
Topics: Humans; Aldosterone; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Heart Failure; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Potassium; Renin-Angiotensin System
PubMed: 38012095
DOI: 10.1002/ehf2.14588 -
The Cochrane Database of Systematic... Jun 2014Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are widely used in peritoneal dialysis (PD) patients, yet controversy exists... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are widely used in peritoneal dialysis (PD) patients, yet controversy exists about their impact on residual kidney function.
OBJECTIVES
This review aimed to evaluate the benefits and harms of ACEis and ARBs for preserving residual kidney function in PD patients.
SEARCH METHODS
The Cochrane Renal Group's specialised register, Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE (OvidSP interface), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI) and other resources were searched by applying a prespecified comprehensive search strategy. Date of last search: 01 May 2014.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs comparing ACEis or ARBs with placebo, other antihypertensive drugs or each other in PD patients were included.
DATA COLLECTION AND ANALYSIS
Screening, selection, data extraction and quality assessments for each retrieved article were carried out by two authors using standardised forms. Authors were contacted when published data were incomplete. Statistical analyses were performed using the random effects model and results expressed as risk ratio (RR) with 95% confidence intervals (CI). Heterogeneity among studies was explored using the Cochran Q statistic and the I² test, subgroup analyses and random effects meta-regression.
MAIN RESULTS
Six open-label studies (257 patients) were identified. One study compared ACEi with other antihypertensive drugs, three compared ARBs with other antihypertensive drugs, and two studies compared an ARB with an ACEi. Long-term use (≥ 12 months) of an ARB showed significantly benefit of preserving residual kidney function in continuous ambulatory PD (CAPD) patients (MD 1.11 mL/min/1.73 m², 95% CI 0.38 to 1.83), although there was no significant benefit when an ARB were used short-term (≤ six months). One study showed that compared with other antihypertensive drugs, long-term use (12 months) of the ACEi ramipril showed a significant reduction in the decline of residual kidney function in patients on CAPD (MD -0.93 mL/min/1.73m², 95% CI -0.75 to -0.11), and delayed the progression to complete anuria (RR 0.64, 95% CI 0.41 to 0.99). There was no significant difference in serum potassium, urinary protein excretion, Kt/V, weekly creatinine clearance and blood pressure for ARBs versus other antihypertensive drugs. Compared with other antihypertensive drugs, ramipril showed no difference in mortality and cardiovascular events. Compared with an ACEi, ARBs did not show any difference in residual kidney function.The selection bias assessment was low in four studies and unclear in two. Five studies were open-label; however the primary outcome (residual kidney function) was obtained objectively from laboratory tests, and were not likely to be influenced by the lack of blinding. Reporting bias was unclear in all six studies.
AUTHORS' CONCLUSIONS
Compared with other antihypertensive drugs, long-term use (≥ 12 months) of ACEis or ARBs showed additional benefits of preserving residual kidney function in CAPD patients. There was no significant difference on residual kidney function preservation between ARBs and ACEis. However, limited by the small number of RCTs enrolling small number of participants, there is currently insufficient evidence to support the use of an ACEi or an ARB as first line antihypertensive therapy in PD patients.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Disease Progression; Humans; Kidney; Kidney Failure, Chronic; Peritoneal Dialysis; Randomized Controlled Trials as Topic
PubMed: 24953826
DOI: 10.1002/14651858.CD009120.pub2 -
British Journal of Clinical Pharmacology Aug 2022To update our previously reported systematic review and meta-analysis of observational studies on cardiovascular drug exposure and COVID-19 clinical outcomes by focusing... (Meta-Analysis)
Meta-Analysis Review
AIMS
To update our previously reported systematic review and meta-analysis of observational studies on cardiovascular drug exposure and COVID-19 clinical outcomes by focusing on newly published randomized controlled trials (RCTs).
METHODS
More than 500 databases were searched between 1 November 2020 and 2 October 2021 to identify RCTs that were published after our baseline review. One reviewer extracted data with other reviewers verifying the extracted data for accuracy and completeness.
RESULTS
After screening 22 414 records, we included 24 and 21 RCTs in the qualitative and quantitative syntheses, respectively. The most investigated drug classes were angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blocker (ARBs) and anticoagulants, investigated by 10 and 11 studies respectively. In meta-analyses, ACEI/ARBs did not affect hospitalization length (mean difference -0.42, 95% confidence interval [CI] -1.83; 0.98 d, n = 1183), COVID-19 severity (risk ratio/RR 0.90, 95% CI 0.71; 1.15, n = 1661) or mortality (risk ratio [RR] 0.92, 95% CI 0.58; 1.47, n = 1646). Therapeutic anticoagulation also had no effect (hospitalization length mean difference -0.29, 95% CI -1.13 to 0.56 d, n = 1449; severity RR 0.86, 95% CI 0.70; 1.04, n = 2696; and, mortality RR 0.93, 95% CI 0.77; 1.13, n = 5689). Other investigated drug classes were antiplatelets (aspirin, 2 trials), antithrombotics (sulodexide, 1 trial), calcium channel blockers (amlodipine, 1 trial) and lipid-modifying drugs (atorvastatin, 1 trial).
CONCLUSION
Moderate- to high-certainty RCT evidence suggests that cardiovascular drugs such as ACEIs/ARBs are not associated with poor COVID-19 outcomes, and should therefore not be discontinued. These cardiovascular drugs should also not be initiated to treat or prevent COVID-19 unless they are needed for an underlying currently approved therapeutic indication.
Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiovascular Agents; Humans; Observational Studies as Topic; Randomized Controlled Trials as Topic; COVID-19 Drug Treatment
PubMed: 35322889
DOI: 10.1111/bcp.15331