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BMJ (Clinical Research Ed.) Apr 2011To evaluate the cardiovascular outcomes and other outcomes associated with angiotensin receptor blockers. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To evaluate the cardiovascular outcomes and other outcomes associated with angiotensin receptor blockers.
DESIGN
Systematic review of randomised controlled trials with meta-analysis and trial sequential analysis (TSA).
DATA SOURCES AND STUDY SELECTION
Pubmed, Embase, and CENTRAL searches for randomised clinical trials, until August 2010, of angiotensin receptor blockers compared with controls (placebo/active treatment) that enrolled at least 100 participants and had a follow-up of at least one year.
DATA EXTRACTION
Myocardial infarction, death, cardiovascular death, angina pectoris, stroke, heart failure, and new onset diabetes.
RESULTS
37 randomised clinical trials included 147,020 participants and had a total follow-up of 485,166 patient years. When compared with controls (placebo/active treatment), placebo, or active treatment, angiotensin receptor blockers were not associated with an increase in the risk of myocardial infarction (relative risk 0.99, 95% confidence interval 0.92 to 1.07), death, cardiovascular death, or angina pectoris. Compared with controls, angiotensin receptor blockers were associated with a reduction in the risk of stroke (0.90, 0.84 to 0.98), heart failure (0.87, 0.81 to 0.93), and new onset diabetes (0.85, 0.78 to 0.93), with similar results when compared with placebo or with active treatment. Based on trial sequential analysis, there is no evidence even for an average 5.0-7.5% (upper confidence interval 5-11%) relative increase in myocardial infarction (absolute increase of 0.3%), death, or cardiovascular death with firm evidence for relative risk reduction of stroke (at least 1%, average 10%) (compared with placebo only), heart failure (at least 5%, average 10%), and new onset diabetes (at least 4%, average 10%) with angiotensin receptor blockers compared with controls.
CONCLUSIONS
This large and comprehensive analysis produced firm evidence to refute the hypothesis that angiotensin receptor blockers increase the risk of myocardial infarction (ruling out even a 0.3% absolute increase). Compared with controls, angiotensin receptor blockers reduce the risk of stroke, heart failure, and new onset diabetes.
Topics: Adult; Aged; Angiotensin Receptor Antagonists; Diabetes Mellitus; Heart Failure; Humans; Hypertension; Middle Aged; Myocardial Infarction; Prognosis; Randomized Controlled Trials as Topic; Risk Factors; Stroke
PubMed: 21521728
DOI: 10.1136/bmj.d2234 -
International Journal of Molecular... Jul 2023Despite recent advances in heart failure (HF) therapy, the risk of cardiovascular (CV) mortality, morbidity, and HF hospitalization (HFH) are major challenges in HF... (Review)
Review
Despite recent advances in heart failure (HF) therapy, the risk of cardiovascular (CV) mortality, morbidity, and HF hospitalization (HFH) are major challenges in HF treatment. We aimed to review the potential of vericiguat as a treatment option for HF. A systematic literature review was performed using the PubMed database and ClinicalTrials.gov. Four randomized controlled trials were identified, which study the safety and efficacy of vericiguat in HF patients. Vericiguat activates soluble guanylate cyclase (sGC) by binding to the beta-subunit, bypassing the requirement for NO-induced activation. The nitric oxide (NO)-sGC-cyclic guanosine monophosphate (cGMP) pathway plays an essential role in cardiovascular (CV) regulation and the protection of healthy cardiac function but is impaired in HF. Vericiguat reduced the risk of CV death and HFH in HF patients with reduced ejection fraction (HFrEF) but showed no therapeutic effect on HF with preserved ejection fraction (HFpEF). The trials demonstrated a favorable safety profile with most common adverse events such as hypotension, syncope, and anemia. Therefore, vericiguat is recommended for patients with HFrEF and a minimum systolic blood pressure of 100 mmHg. Treatment with vericiguat is considered when the individual patient experiences decompensation despite being on guideline-recommended medication, e.g., angiotensin-converting inhibitor/AT1 receptor antagonist, beta-adrenoceptor antagonist, spironolactone, and sodium-glucose transporter 2 inhibitors. Furthermore, larger studies are required to investigate any potential effect of vericiguat in HFpEF patients. Despite the limitations, vericiguat can be recommended for patients with HFrEF, where standard-of-care is insufficient, and the disease worsens.
Topics: Humans; Heart Failure; Treatment Outcome; Stroke Volume; Soluble Guanylyl Cyclase; Cardiotonic Agents; Diuretics
PubMed: 37511587
DOI: 10.3390/ijms241411826 -
BMJ Clinical Evidence Mar 2012Among people with diabetes, about 40% of those aged 45 years, and more than 60% of those aged 75 years or over, will have a blood pressure over 140/90 mmHg. Major... (Review)
Review
INTRODUCTION
Among people with diabetes, about 40% of those aged 45 years, and more than 60% of those aged 75 years or over, will have a blood pressure over 140/90 mmHg. Major cardiac events occur in approximately 5% of people with diabetes and untreated hypertension each year, and the risk is higher in those with other risk factors, such as diabetic nephropathy.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of antihypertensives in people with diabetes and hypertension? What are the effects of different blood pressure targets in people with diabetes and hypertension? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 24 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: alpha-blockers, angiotensin II receptor antagonists, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, blood pressure targets (lower or higher), calcium-channel blockers, and diuretics.
Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Humans; Hypertension
PubMed: 22456232
DOI: No ID Found -
European Heart Journal. Cardiovascular... Mar 2021Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) share their target receptor site with the SARS-CoV-2 virus, that may cause ACE2... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) share their target receptor site with the SARS-CoV-2 virus, that may cause ACE2 receptor up-regulation which raised concerns regarding ACEI and ARB use in COVID-19 patients. However, many medical professional societies recommended their continued use given the paucity of clinical evidence, but there is a need for an updated systematic review and meta-analysis of the latest clinical studies.
METHODS AND RESULTS
A search was conducted on PubMed, Google Scholar, EMBASE, and various preprint servers for studies comparing clinical outcomes and mortality in COVID-19 patients on ACEIs and/or ARBs, and a meta-analysis was performed. A total of 16 studies were included for the review and meta-analysis. There were conflicting findings reported in the rates of severity and mortality in several studies. In a pooled analysis of four studies, there was a statistically non-significant association of ACEI/ARB use with lower odds of developing severe disease vs. non-users [odds ratio (OR) = 0.81, 95% confidence interval (CI): 0.41-1.58, I2=50.52, P-value = 0.53). In a pooled analysis of six studies, there was a statistically non-significant association of ACEI/ARB use with lower odds of mortality as compared with non-users (OR = 0.86, 95% CI = 0.53-1.41, I2 = 79.12, P-value = 0.55).
CONCLUSION
It is concluded that ACEIs and ARBs should be continued in COVID-19 patients, reinforcing the recommendations made by several medical societies. Additionally, the individual patient factors such as ACE2 polymorphisms which might confer higher risk of adverse outcomes need to be evaluated further.
Topics: Adult; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; COVID-19; Humans; Middle Aged; SARS-CoV-2; Severity of Illness Index
PubMed: 32542337
DOI: 10.1093/ehjcvp/pvaa064 -
Oncotarget Feb 2016Emerging evidence suggests that renin-angiotensin system (RAS) may act as a molecular and therapeutic target for treating site-specific cancers, including prostate... (Meta-Analysis)
Meta-Analysis Review
Emerging evidence suggests that renin-angiotensin system (RAS) may act as a molecular and therapeutic target for treating site-specific cancers, including prostate cancer. However, previous observational studies regarding the association between RAS inhibitors and prostate cancer risk have reported inconsistent results. We examined this association by performing a systematic review and meta-analysis. A total of 20,267 patients from nine cohort studies were enrolled. Compared with non-users of RAS inhibitors, individuals using RAS inhibitors had a reduced risk of prostate cancer (RR 0.92, 95 % CI 0.87-0.98), without statistically significant heterogeneity among studies (P = 0.118 for heterogeneity, I2 = 37.6 %). In addition, when subgroup analyses by study quality and number of cases, more statistically significant associations were observed in studies of high quality (RR 0.93, 95 % CI 0.88-0.97) and large sample size (RR 0.94, 95 % CI 0.91-0.98). There was no evidence of significant publication bias with Begg's test (P = 0.602) or with Egger's test (P = 0.350). Overall, this study indicates that use of RAS inhibitors may be associated with a decreased risk of prostate cancer. Large-scale well designed studies are needed to further explore this association.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cohort Studies; Humans; Male; Prostatic Neoplasms
PubMed: 26760503
DOI: 10.18632/oncotarget.6837 -
Singapore Medical Journal Nov 2021There are concerns that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may worsen the outcomes of patients with COVID-19. This... (Meta-Analysis)
Meta-Analysis
Impact of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on in-hospital mortality among patients with COVID-19: a systematic review and meta-analysis.
INTRODUCTION
There are concerns that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may worsen the outcomes of patients with COVID-19. This systematic review and meta-analysis aimed to study the in-hospital mortality among COVID-19 patients who were on ACEIs/ARBs as compared to those not on ACEIs/ARBs.
METHODS
We searched PubMed, EMBASE, clinicaltrials.gov and Google Scholar between 1 January 2020 and 30 May 2020 to identify all studies that evaluated the use of ACEIs/ARBs and reported the in-hospital mortality outcomes of COVID-19 patients. Nine non-randomised studies were eligible for inclusion in the analysis. The primary outcome studied was the in-hospital mortality of COVID-19 patients who were on ACEIs/ARBs compared with those not on ACEIs/ARBs.
RESULTS
Of the 8,313 patients in the nine studies, 7,622 (91.7%) were from studies with all-comers, while 691 (8.3%) were from studies involving only patients with hypertension. 577 (14.6%) in-hospital deaths were observed out of a total of 3,949 patients with an outcome in the nine studies. Overall, no significant difference was observed in the in-hospital mortality between patients on ACEIs/ARBs and those not on ACEIs/ARBs (odds ratio [OR] 1.06, 95% confidence interval [CI] 0.75-1.50; p = 0.73). Further sensitivity analysis in the hypertension group and the all-comers group showed similar results (OR 0.88, 95% CI 0.58-1.32; p = 0.53 and OR 1.85, 95% CI 1.00-3.43; p = 0.05, respectively).
CONCLUSION
We observed that ACEIs/ARBs had no significant impact on the in-hospital mortality of COVID-19 patients and can be used safely in patients with indications.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; COVID-19; Hospital Mortality; Humans; Hypertension; SARS-CoV-2
PubMed: 33256355
DOI: 10.11622/smedj.2020159 -
Journal of the American Heart... Jun 2022Background Renin-angiotensin aldosterone system (RAAS) inhibitor-COVID-19 studies, observational in design, appear to use biased methods that can distort the interaction... (Meta-Analysis)
Meta-Analysis Review
Background Renin-angiotensin aldosterone system (RAAS) inhibitor-COVID-19 studies, observational in design, appear to use biased methods that can distort the interaction between RAAS inhibitor use and COVID-19 risk. This study assessed the extent of bias in that research and reevaluated RAAS inhibitor-COVID-19 associations in studies without critical risk of bias. Methods and Results Searches were performed in MEDLINE, EMBASE, and CINAHL databases (December 1, 2019 to October 21, 2021) identifying studies that compared the risk of infection and/or severe COVID-19 outcomes between those using or not using RAAS inhibitors (ie, angiotensin-converting enzyme inhibitors or angiotensin II type-I receptor blockers). Weighted hazard ratios (HR) and 95% CIs were extracted and pooled in fixed-effects meta-analyses, only from studies without critical risk of bias that assessed severe COVID-19 outcomes. Of 169 relevant studies, 164 had critical risks of bias and were excluded. Ultimately, only two studies presented data relevant to the meta-analysis. In 1 351 633 people with uncomplicated hypertension using a RAAS inhibitor, calcium channel blocker, or thiazide diuretic in monotherapy, the risk of hospitalization (angiotensin-converting enzyme inhibitor: HR, 0.76; 95% CI, 0.66-0.87; <0.001; angiotensin II type-I receptor blockers: HR, 0.86; 95% CI, 0.77-0.97; =0.015) and intubation or death (angiotensin-converting enzyme inhibitor: HR, 0.64; 95% CI, 0.48-0.85; =0.002; angiotensin II type-I receptor blockers: HR, 0.74; 95% CI, 0.58-0.95; =0.019) with COVID-19 was lower in those using a RAAS inhibitor. However, these protective effects are probably not clinically relevant. Conclusions This study reveals the critical risk of bias that exists across almost an entire body of COVID-19 research, raising an important question: Were research methods and/or peer-review processes temporarily weakened during the surge of COVID-19 research or is this lack of rigor a systemic problem that also exists outside pandemic-based research? Registration URL: www.crd.york.ac.uk/prospero/; Unique identifier: CRD42021237859.
Topics: Aldosterone; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; COVID-19; Humans; Hypertension; Renin; Renin-Angiotensin System; SARS-CoV-2
PubMed: 35624081
DOI: 10.1161/JAHA.122.025289 -
Frontiers in Immunology 2023The incidence and risk factors of acute kidney injury (AKI) in patients with malignancies receiving immune checkpoint inhibitors (ICIs) are being extensively reported... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The incidence and risk factors of acute kidney injury (AKI) in patients with malignancies receiving immune checkpoint inhibitors (ICIs) are being extensively reported with their widespread application.
OBJECTIVE
This study aimed to quantify the incidence and identify risk factors of AKI in cancer patients treated with ICIs.
METHODS
We searched the electronic databases of PubMed/Medline, Web of Science, Cochrane and Embase before 1 February 2023 on the incidence and risk factors of AKI in patients receiving ICIs and registered the protocol in PROSPERO (CRD42023391939). A random-effect meta-analysis was performed to quantify the pooled incidence estimate of AKI, identify risk factors with pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) and investigate the median latency period of ICI-AKI in patients treated with ICIs. Assessment of study quality, meta-regression, and sensitivity and publication bias analyses were conducted.
RESULTS
In total, 27 studies consisting of 24048 participants were included in this systematic review and meta-analysis. The overall pooled incidence of AKI secondary to ICIs was 5.7% (95% CI: 3.7%-8.2%). Significant risk factors were older age (OR: 1.01, 95% CI: 1.00-1.03), preexisting chronic kidney disease (CKD) (OR: 2.90, 95% CI: 1.65-5.11), ipilimumab (OR: 2.66, 95% CI: 1.42-4.98), combination of ICIs (OR: 2.45, 95% CI: 1.40-4.31), extrarenal immune-related adverse events (irAEs) (OR: 2.34, 95% CI: 1.53-3.59), and proton pump inhibitor (PPI) (OR: 2.23, 95% CI: 1.88-2.64), nonsteroidal anti-inflammatory drug (NSAID) (OR: 2.61, 95% CI: 1.90-3.57), fluindione (OR: 6.48, 95% CI: 2.72-15.46), diuretic (OR: 1.78, 95% CI: 1.32-2.40) and angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) (pooled OR: 1.76, 95% CI: 1.15-2.68) use. Median time from ICIs initiation to AKI was 108.07 days. Sensitivity and publication bias analyses indicated robust results for this study.
CONCLUSION
The occurrence of AKI following ICIs was not uncommon, with an incidence of 5.7% and a median time interval of 108.07 days after ICIs initiation. Older age, preexisting chronic kidney disease (CKD), ipilimumab, combined use of ICIs, extrarenal irAEs, and PPI, NSAID, fluindione, diuretics and ACEI/ARB use are risk factors for AKI in patients receiving ICIs.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023391939.
Topics: Humans; Immune Checkpoint Inhibitors; Ipilimumab; Angiotensin Receptor Antagonists; Incidence; Angiotensin-Converting Enzyme Inhibitors; Neoplasms; Acute Kidney Injury; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 37313406
DOI: 10.3389/fimmu.2023.1173952 -
Nephrology, Dialysis, Transplantation :... Oct 2023Dual renin-angiotensin-aldosterone system (RAAS) blockade involves dual therapy with a combination of angiotensin-converting enzyme inhibitors (ACEis),... (Meta-Analysis)
Meta-Analysis
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.
BACKGROUND AND OBJECTIVES
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 chronic kidney disease (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.
DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS
This is a systematic review and meta-analysis of the randomized controlled trials (RCT) published from 1 January 2006 to 30 May 2022. The study population included adult patients with DKD receiving dual RAAS blockade. A total of 31 RCTs and 33 048 patients were included in the systematic review. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random effects.
RESULTS
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 five events in 248 at risk in monotherapy (pooled RR 5.42 95% CI: 2.15-13.67).
CONCLUSION
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.
Topics: Adult; Humans; Renin-Angiotensin System; Diabetic Nephropathies; Hyperkalemia; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Acute Kidney Injury; Diabetes Mellitus
PubMed: 37309038
DOI: 10.1093/ndt/gfad101 -
American Journal of Ophthalmology Nov 2023We synthesized the literature on the association between systemic antihypertensive medications with intraocular pressure (IOP) and glaucoma. Antihypertensive medications... (Review)
Review
PURPOSE
We synthesized the literature on the association between systemic antihypertensive medications with intraocular pressure (IOP) and glaucoma. Antihypertensive medications included β-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and diuretics.
DESIGN
Systematic review and meta-analysis.
METHODS
Databases were searched for relevant articles until December 5, 2022. Studies were eligible if they examined (1) the association between systemic antihypertensive medications with glaucoma or (2) the association between systemic antihypertensive medications with IOP in those without glaucoma or ocular hypertension. The protocol was registered at PROSPERO (International Prospective Register of Systematic Reviews; registration ID: CRD42022352028).
RESULTS
A total of 11 studies were included in the review and 10 studies in the meta-analysis. The 3 studies on IOP were cross-sectional, whereas the 8 studies on glaucoma were primarily longitudinal. In the meta-analysis, β-blockers were associated with a lower odds of glaucoma (odds ratio: 0.83, 95% CI: 0.75-0.92, 7 studies, n = 219,535) and lower IOP (β: -0.53, 95% CI: -1.05 to -0.02, 3 studies, n = 28,683). Calcium channel blockers were associated with a higher odds of glaucoma (odds ratio: 1.13, 95% CI: 1.03-1.24, 7 studies, n = 219,535) but not with IOP (β: -0.11, 95% CI: -0.25 to 0.03, 2 studies, n = 20,620). There were no consistent associations between angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or diuretics with glaucoma or IOP.
CONCLUSIONS
Systemic antihypertensive medications have heterogeneous effects on glaucoma and IOP. Clinicians should be aware that systemic antihypertensive medications may mask elevated IOP or positively or negatively affect the risk of glaucoma.
PubMed: 36966883
DOI: 10.1016/j.ajo.2023.03.014