-
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 -
Phytomedicine : International Journal... Jan 2023The therapeutic benefits of Niaoduqing granules (NDQG) in kidney diseases has been comprehensively studied, but its adverse drug reactions remain unexplored. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The therapeutic benefits of Niaoduqing granules (NDQG) in kidney diseases has been comprehensively studied, but its adverse drug reactions remain unexplored.
OBJECTIVE
To evaluate the safety of NDQG in kidney disease treatment.
METHODS
The literature was searched in Embase, Medline via PubMed, Cochrane Library database, Wanfang database, Chinese National Knowledge Infrastructure, SinoMed, and Chinese VIP Database from inception to January 15, 2022, for randomized controlled trials (RCTs) and observational studies. The ClinicalTrials.gov website was searched for ongoing trials. The frequency and characteristics of adverse drug reactions (ADRs) were the primary and secondary outcomes, respectively. Subgroup analysis were conducted to explore the effects of clinical trial types, different kidney diseases, drug combinations and dosage on the safety of NDQG.
RESULTS
This review included 132 trials comprising 115 RCTs and 17 cohort studies. Additionally, 118 studies reported ADR rates with complete data, including 10381 participants. Regarding ADR frequency, no significant difference was observed between NDQG (7.26%) and control (8.39%) groups (RR = 0.890, 95% confidence interval (CI): 0.788-1.007); with no heterogeneity among the studies (I = 0.0%, P = 0.958). ADR frequency in patients with chronic kidney disease (65 trials, n = 5823) was significantly lower in the NDQG treatment group than in the control group (RR = 0.810, 95% CI: 0.67-0.969, I = 0.0%, P = 0.993); however, for patients with diabetic nephropathy there was no difference between both groups (26 trials, n = 2166, RR = 1.077, 95% CI: 0.802-1.446, I = 0.0%, P = 0.611). Similarly, the incidence of ADR in patients on dialysis and patients with pyelonephritis and nephrotic syndrome was the same for both groups, with 95% CI overlapping the line. For different interventions, including NDQG monotherapy or its combination with other commonly used drugs (including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statin drugs, and compound α-keto acid) or dialysis, the incidence of ADR showed no significant difference between the experimental and control arms. The ADR in the NDQG group primarily affected the gastrointestinal system (64.74%), central and peripheral nervous system (9.07%), whole body (5.79%), and skin and appendages (4.53%). The most common clinical manifestations were diarrhea, nausea, and vomiting.
CONCLUSIONS
Our meta-analysis showed that compared with supportive therapy, the incidence of ADR was similar when NDQG was added. However, current evidence is not definitive and more well-designed and conducted RCTs are warranted to definitively establish the reliable evidence.
PROTOCOL REGISTRATION NUMBER
PROSPERO CRD 42018104227.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Renal Insufficiency, Chronic; Nephrotic Syndrome; Skin; Drug-Related Side Effects and Adverse Reactions
PubMed: 36610168
DOI: 10.1016/j.phymed.2022.154535 -
Renin-Angiotensin-Aldosterone System Inhibitors and COVID-19: A Meta-Analysis and Systematic Review.Cureus Feb 2021Introduction Increased virulence, the severity of illness, and mortality have all been hypothesized with respect to angiotensin-converting enzyme inhibitor...
Introduction Increased virulence, the severity of illness, and mortality have all been hypothesized with respect to angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) use in coronavirus disease 2019 (COVID-19) infection. Our study aims to assess whether ACEi/ARB use in patients with COVID-19 conferred worsened severity of illness or increased mortality. Additionally, we explore the possibility of an unearthed protective benefit due to their interruption of the RAS signaling pathway as observed in cardiovascular diseases. Methods The Cochrane Library, MEDLINE, and EMBASE were searched for studies relevant to COVID-19 severity, mortality, and inflammation in the context of ACEi/ARB use. Eight studies were included with a total of 17,943 patients, 4,292 (23.9%) of which were taking an ACEi or an ARB. The study population was 47.9% female and the average age across all studies was 65. The studies chosen had a sample size of at least 100 patients. Results Mortality outcomes were assessed in six studies and showed no significant difference in mortality among the ACEi/ARB and control groups (odds ratio [OR]: 0.99, 95%CI: 0.48-2.04). Seven studies assessed the severity of COVID-19 and showed no statistically significant difference in disease severity when comparing the ACEi/ARB group to the control group (odds ratio [OR]: 1.30, 95% CI 0.87-1.94). Four studies reported the length of stay with no significant difference between the ACEi/ARB groups as compared to non-users. Four studies included inflammatory markers C-reactive protein (CRP) and D-Dimer, which were noted to be consistently lower in the ACEi/ARB groups when compared to control groups, however, this was not statistically significant. Conclusion Our study found no significant difference in mortality, severity of illness, or length of stay between ACEi/ARB users and non-users with COVID-19 infection. These results support the continuation of ACEi and ARBs in the setting of COVID-19 as advised by the American College of Cardiology (ACC)/American Heart Association (AHA). The decrease in CRP and D-dimer suggests a possible protective effect related to ACEi/ARB use in COVID-19, however, more studies with larger sample sizes are needed to establish this effect.
PubMed: 33728141
DOI: 10.7759/cureus.13124 -
Cureus Aug 2023Amyloid-ß (Aß) plaques and Neurofibrillary tangles are hallmarks of Alzheimer's disease (AD) pathology. Recent advances to find a cure for AD have led to the... (Review)
Review
Comparative Study of Safety and Efficacy of Angiotensin-Receptor Blockers and Anti Amyloid-ß Monoclonal Antibodies for the Treatment of Alzheimer's Disease: A Systematic Review.
Amyloid-ß (Aß) plaques and Neurofibrillary tangles are hallmarks of Alzheimer's disease (AD) pathology. Recent advances to find a cure for AD have led to the exploration of Anti-Aß monoclonal antibodies and angiotensin-receptor blockers (ARBs). The antibodies can decrease plaque formation or remove already formed plaques. ARBs increase angiotensin II (AT2) levels and decrease the effect of AT2 on the AT1 receptor (AT1R). This systematic analysis reviews evidence of monoclonal antibodies (Aducanumab, Lecanemab, Donanemab, and Solanezumab) and ARBs in managing AD. An in-depth methodical search was conducted across PubMed, Science Direct, and Mendeley. PRISMA 2020 guidelines were followed for this study. Randomized control trials for antibodies and ARBs and one retrospective cohort study were included. The comparison was made among studies that shared similar measured outcomes. Antibodies were found to be more effective than ARBs, with Aducanumab and Lecanemab being the most effective. ARBs, on the other hand, were found to be the safer choice. Further trials of longer duration and larger sample sizes are needed to explore both groups' long-term safety and efficacy.
PubMed: 37746412
DOI: 10.7759/cureus.43984 -
Journal of Clinical Hypertension... May 2021Angiotensin-receptor blockers are often considered insufficiently efficacious in reducing blood pressure. However, newer angiotensin-receptor blockers may be more... (Meta-Analysis)
Meta-Analysis
Is the newest angiotensin-receptor blocker azilsartan medoxomil more efficacious in lowering blood pressure than the older ones? A systematic review and network meta-analysis.
Angiotensin-receptor blockers are often considered insufficiently efficacious in reducing blood pressure. However, newer angiotensin-receptor blockers may be more effective than the older ones. A network meta-analysis was performed to compare the efficacy of various angiotensin-receptor blockers in reducing office and ambulatory blood pressure in hypertensive patients. Relevant literature was searched from English and Chinese databases for randomized controlled trials involving angiotensin-receptor blockers in hypertension. Efficacy variables included systolic and diastolic blood pressure either in the office or on ambulatory blood pressure monitoring. Absolute blood pressure reductions at 6-12 weeks of treatment and their credible intervals were reported. A total of 34 publications provided adequate data for analysis (n = 14 859). In 28 studies on office systolic blood pressure (n = 12 731), against the common comparator valsartan 80 mg, the differences in systolic blood pressure were in favor of azilsartan medoxomil (20-80 mg), irbesartan (300 mg), olmesartan (20-40 mg), telmisartan (80 mg), and valsartan (160-320 mg), but not candesartan (8-16 mg), losartan (50-100 mg), irbesartan (150 mg), olmesartan (10 mg), and telmisartan (40 mg). The ranking plot shows that azilsartan medoxomil 80 mg had a possibility of 99% being the best in the class. Similar results were observed for office diastolic blood pressure and from 13 studies for 24-hour ambulatory systolic and diastolic blood pressure. In conclusion, angiotensin-receptor blockers had different blood pressure lowering efficacy. The newest angiotensin-receptor blocker azilsartan medoxomil at the dose of 80 mg seemed to be most efficacious in reducing both systolic and diastolic blood pressure in the office and on ambulatory measurement.
Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensins; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Humans; Hypertension; Network Meta-Analysis; Olmesartan Medoxomil; Oxadiazoles; Tetrazoles
PubMed: 33609077
DOI: 10.1111/jch.14227 -
Archives of Medical Science : AMS 2023Heart failure (HF) is still a major cause of morbidity and mortality all over the world. Aim of the study was to assess the benefits and harms of sacubitril/valsartan... (Review)
Review
Efficacy and safety of sacubitril/valsartan in heart failure compared to renin-angiotensin-aldosterone system inhibitors: a systematic review and meta-analysis of randomised controlled trials.
INTRODUCTION
Heart failure (HF) is still a major cause of morbidity and mortality all over the world. Aim of the study was to assess the benefits and harms of sacubitril/valsartan (S/V) compared to angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) in patients with HF.
MATERIAL AND METHODS
We systematically searched for randomised controlled trials (RCTs) evaluating S/V vs. ACEI or ARB in acute or chronic HF in August 2021. Primary outcomes were HF hospitalisations and cardiovascular (CV) mortality; secondary outcomes included all-cause mortality, biomarkers, and renal function.
RESULTS
We selected 11 RCTs ( = 18766) with 2-48 months follow-up. Five RCTs had ACEIs as control, 5 RCTs had ARBs as control, and one RCT had both ACEI and ARB as control. Compared to ACEI or ARB, S/V reduced HF hospitalisations by 20% (HR = 0.80, 95% CI: 0.68-0.94; 3 RCTs; = 65%; high CoE), CV mortality by 14% (HR = 0.86, 95% CI: 0.73-1.01; 2 RCTs; = 57%; high CoE), and all-cause mortality by 11% (HR = 0.89, 95% CI: 0.78-1.00; 3 RCTs; = 36%; high CoE). S/V reduced NTproBNP (SMD = -0.34, 95% CI: -0.52 to -0.16; 3 RCTs; = 62%) and hs-TNT (ratio of differences = 0.84, 95% CI: 0.79-0.88; 2 RCTs; = 0%), and caused a decline in renal function by 33% (HR = 0.67, 95% CI: 0.39-1.14; 2 RCTs; = 78%; high CoE). S/V increased hypotension (RR = 1.69, 95% CI: 1.33-2.15; 9 RCTs; = 65%; high CoE). Hyperkalaemia and angioedema events were similar. Effects were in the same direction when stratified by type of control (ACEI vs. ARB).
CONCLUSIONS
Sacubitril/valsartan had better clinical, intermediate, and renal outcomes in HF in comparison to ACEI or ARB. There was no difference in angioedema and hyperkalaemia events, but there were more hypotension events.
PubMed: 37313196
DOI: 10.5114/aoms/159113 -
Journal of Personalized Medicine Sep 2021COVID-2019 pandemic lead to a raised interest on the development of new treatments through Artificial Intelligence (AI). (Review)
Review
BACKGROUND
COVID-2019 pandemic lead to a raised interest on the development of new treatments through Artificial Intelligence (AI).
AIM
to carry out a systematic review on the development of repurposed drugs against COVID-2019 through the application of AI.
METHODS
The Systematic Reviews and Meta-Analyses (PRISMA) checklist was applied.
KEYWORDS
["Artificial intelligence" and (COVID or SARS) and (medicine or drug)]. Databases: PubMed, DOAJ and SciELO. Cochrane Library was additionally screened to identify previous published reviews on the same topic.
RESULTS
From the 277 identified records [PubMed (n = 157); DOAJ ( = 119) and SciELO ( = 1)], 27 studies were included. Among other, the selected studies on new treatments against COVID-2019 were classified, as follows: studies with in-vitro and/or clinical data; association of known drugs; and other studies related to repurposing of drugs.
CONCLUSION
Diverse potentially repurposed drugs against COVID-2019 were identified. The repurposed drugs were mainly from antivirals, antibiotics, anticancer, anti-inflammatory, and Angiotensin-converting enzyme 2 (ACE2) groups, although diverse other pharmacologic groups were covered. AI was a suitable tool to quickly analyze large amounts of data or to estimate drug repurposing against COVID-2019.
PubMed: 34575703
DOI: 10.3390/jpm11090926 -
Gene Nov 2022The COVID-19 pandemic has spawned global health crisis of unprecedented magnitude, claiming millions of lives and pushing healthcare systems in many countries to the... (Meta-Analysis)
Meta-Analysis Review
The COVID-19 pandemic has spawned global health crisis of unprecedented magnitude, claiming millions of lives and pushing healthcare systems in many countries to the brink. Among several factors that contribute to an increased risk of COVID-19 and progression to exacerbated manifestations, host genetic landscape is increasingly being recognized as a critical determinant of susceptibility/resistance to infection and a prognosticator of clinical outcomes in infected individuals. Recently, several case-control association studies investigated the influence of human gene variants on COVID-19 susceptibility and severity to identify the culpable mutations. However, a comprehensive synthesis of the recent advances in COVID-19 host genetics research was lacking, and the inconsistent findings of the association studies required reliable evaluation of the strength of association with greater statistical power. In this study, we embarked on a systematic search of all possible reports of genetic association with COVID-19 till April 07, 2022, and performed meta-analyses of all the genetic polymorphisms that were examined in at least three studies. After identifying a total of 84 studies that investigated the association of 130 polymorphisms in 61 genes, we performed meta-analyses of all the eligible studies. Seven genetic polymorphisms involving 15,550 cases and 444,007 controls were explored for association with COVID-19 susceptibility, of which, ACE1 I/D rs4646994/rs1799752, APOE rs429358, CCR5 rs333, and IFITM3 rs12252 showed increased risk of infection. Meta-analyses of 11 gene variants involving 6702 patients with severe COVID-19 and 8640 infected individuals with non-severe manifestations revealed statistically significant association of ACE2 rs2285666, ACE2 rs2106809, ACE2 rs2074192, AGTR1 rs5186, and TNFA rs1800629 with COVID-19 severity. Overall, our study presents a synthesis of evidence on all the genetic determinants implicated in COVID-19 to date, and provides evidence of correlation between the above polymorphisms with COVID-19 susceptibility and severity.
Topics: Angiotensin-Converting Enzyme 2; COVID-19; Genetic Predisposition to Disease; Human Genetics; Humans; Membrane Proteins; Pandemics; RNA-Binding Proteins; SARS-CoV-2
PubMed: 35987511
DOI: 10.1016/j.gene.2022.146790 -
Shock (Augusta, Ga.) Jun 2024While non-norepinephrine vasopressors are increasingly used as a rescue therapy in cases of norepinephrine-refractory shock, data on their efficacy are limited. This...
BACKGROUND
While non-norepinephrine vasopressors are increasingly used as a rescue therapy in cases of norepinephrine-refractory shock, data on their efficacy are limited. This systematic review and meta-analysis aims to synthesize existing literature on the efficacy of Angiotensin II (ATII) in distributive shock.
METHODS
We pre-registered our meta-analysis with PROSPERO (CRD42023456136). We searched PubMed, Scopus, and gray literature for studies presenting outcomes on ATII use in distributive shock. The primary outcome of the meta-analysis was all-cause mortality. We used a random effects model to calculate pooled risk ratio (RR) and 95% confidence intervals (CI).
RESULTS
By incorporating data from 1555 patients included in 10 studies, we found that however all-cause mortality was similar among patients receiving ATII and controls (RR 1.02, 95% CI 0.89 to 1.16, p = 0.81), the reduction in norepinephrine or norepinephrine-equivalent dose at 3 h after treatment initiation was greater among patients receiving ATII (MD -0.06, 95% CI -0.11 to -0.02, p = 0.008), while there were no higher rates of adverse events reported among ATII patients.
CONCLUSIONS
While ATII did not reduce mortality among distributive shock patients, it allowed for significant adjunctive vasopressor reduction at 3 h without an increase in reported adverse events, deeming it a viable alternative for the increasingly adopted multimodal vasopressor for minimizing catecholamine exposure and its adverse events.
PubMed: 38888542
DOI: 10.1097/SHK.0000000000002384 -
Neurology, Psychiatry, and Brain... Sep 2020To describe the main neurological manifestations related to coronavirus infection in humans. (Review)
Review
OBJECTIVE
To describe the main neurological manifestations related to coronavirus infection in humans.
METHODOLOGY
A systematic review was conducted regarding clinical studies on cases that had neurological manifestations associated with COVID-19 and other coronaviruses. The search was carried out in the electronic databases PubMed, Scopus, Embase, and LILACS with the following keywords: "coronavirus" or "Sars-CoV-2" or "COVID-19" and "neurologic manifestations" or "neurological symptoms" or "meningitis" or "encephalitis" or "encephalopathy," following the Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
Seven studies were included. Neurological alterations after CoV infection may vary from 17.3% to 36.4% and, in the pediatric age range, encephalitis may be as frequent as respiratory disorders, affecting 11 % and 12 % of patients, respectively. The Investigation included 409 patients diagnosed with CoV infection who presented neurological symptoms, with median age range varying from 3 to 62 years. The main neurological alterations were headache (69; 16.8 %), dizziness (57, 13.9 %), altered consciousness (46; 11.2 %), vomiting (26; 6.3 %), epileptic crises (7; 1.7 %), neuralgia (5; 1.2 %), and ataxia (3; 0.7 %). The main presumed diagnoses were acute viral meningitis/encephalitis in 25 (6.1 %) patients, hypoxic encephalopathy in 23 (5.6 %) patients, acute cerebrovascular disease in 6 (1.4 %) patients, 1 (0.2 %) patient with possible acute disseminated encephalomyelitis, 1 (0.2 %) patient with acute necrotizing hemorrhagic encephalopathy, and 2 (1.4 %) patients with CoV related to Guillain-Barré syndrome.
CONCLUSION
Coronaviruses have important neurotropic potential and they cause neurological alterations that range from mild to severe. The main neurological manifestations found were headache, dizziness and altered consciousness.
PubMed: 32834527
DOI: 10.1016/j.npbr.2020.05.008