A meta-analysis of effects of CYP2C9 and CYP2C19 polymorphisms on phenytoin pharmacokinetic parameters

Aim: Phenytoin is metabolized through CYP2C9 and CYP2C19 . Polymorphisms of CYP2C9 and CYP2C19 may increase plasma concentration and side effects. Materials & methods: Systematic review and meta-analysis were performed to evaluate the effects of CYP2C9 and CYP2C19 polymorphism on pharmacokinetic parameters. PubMed, Science Direct, Cochrane library, and Thai databases were systematically searched. Results: Eight observational studies, comprising a total of 633 patients were included. Michaelis–Menten constant was significantly higher in the polymorphism of CYP2C9IM/CYP2C19EM and CYP2C9IM/CYP2C19IM groups as compared with the control groups (CYP2C9EM/CYP2C19EM) at 2.16 and 1.55 mg/l (p < 0.00001, p < 0.0001). The maximum rate of action was significantly lower in the control groups as compared with the polymorphism of CYP2C9IM/CYP2C19EM and CYP2C9IM/CYP2C19IM groups at 3.10 and 3.53 mg/kg/day (p = 0.00001, <0.0001). Conclusion: The dosage regimen for patients in the CYP2C9IM group to achieve phenytoin therapeutic levels was 2.1–3.4 mg/kg/day.

Download Full-text

Indicated preventive interventions for anxiety in children and adolescents: a review and meta-analysis of school based programs

10.31234/osf.io/jadxq ◽

2019 ◽

Author(s):

Siobhan Hugh-Jones ◽

Sophie Beckett ◽

Pavan Mallikarjun

Keyword(s):

Meta Analysis ◽

Child And Adolescent ◽

Sensitivity Analyses ◽

Cochrane Library ◽

Control Groups ◽

Adolescent Anxiety ◽

School Based ◽

Intervention Intensity ◽

Randomised Controlled ◽

And Control

Schools are promising sites for the delivery of prevention and early intervention programs to reduce child and adolescent anxiety. It is unclear whether universal or targeted approaches are most effective. This review and meta-analysis examines the effectiveness of school-based indicated interventions and was registered with PROSPERO [CRD42018087628].MEDLINE, EMBASE, PsycINFO and the Cochrane Library were searched for randomised controlled trials comparing indicated school programs for child and adolescent anxiety to active or inactive control groups. Twenty original studies, with 2076 participants, met the inclusion criteria and 18 were suitable for meta-analysis. Sub-group and sensitivity analyses explored intervention intensity, delivery agent and control type. A small beneficial effect was found for indicated programs compared to controls on self-reported anxiety symptoms at post-test (g = -0.28, CI = -0.50, -0.05, k= 18). The small effect was maintained at 6 (g = -0.35, CI= -0.58, -0.13, k = 9) and 12 months (g = -0.24, CI = -0.48, 0.00, k = 4). Based on two studies, >12 month effects were very small (g = -0.01, CI= -0.38, 0.36). No differences were found based on intervention intensity, delivery agent and control type. There was evidence of publication bias and a relatively high risk of contamination in studies. Findings support the value of school based indicated programs for child and adolescent anxiety. Effects at 12 months outperform many universal programs. High quality, randomised controlled and pragmatic trials are needed, with attention control groups and beyond 12 month diagnostic assessments are needed.

Download Full-text

Prognostic Value of Serum Magnesium in Mortality Risk among Patients on Hemodialysis: A Meta-Analysis of Observational Studies

Kidney Diseases ◽

10.1159/000510513 ◽

2020 ◽

pp. 1-10

Author(s):

Hongwei Wu ◽

Qiang Li ◽

Lijing Fan ◽

Dewang Zeng ◽

Xianggeng Chi ◽

...

Keyword(s):

Mortality Risk ◽

Cardiovascular Mortality ◽

Observational Studies ◽

Prognostic Value ◽

Meta Analysis ◽

Serum Magnesium ◽

Cochrane Library ◽

Lower Serum ◽

All Cause Mortality ◽

End Stage

Background: Previous studies have reported that serum magnesium (Mg) deficiency is involved in the development of heart failure, particularly in patients with end-stage kidney disease. The association between serum Mg levels and mortality risk in patients receiving hemodialysis is controversial. We aimed to estimate the prognostic value of serum Mg concentration on all-cause mortality and cardiovascular mortality in patients receiving hemodialysis. Methods: We did a systematic literature search in PubMed, EMBASE, Cochrane Library, and Web of Science to identify eligible studies that reported the prognostic value of serum Mg levels in mortality risk among patients on hemodialysis. We performed a meta-analysis by pooling and analyzing hazard ratios (HRs) and 95% confidence intervals (CIs). Results: We identified 13 observational studies with an overall sample of 42,967 hemodialysis patients. Higher all-cause mortality (adjusted HR 1.58 [95% CI: 1.31–1.91]) and higher cardiovascular mortality (adjusted HR 3.08 [95% CI: 1.27–7.50]) were found in patients with lower serum Mg levels after multivariable adjustment. There was marked heterogeneity (I2 = 79.6%, p < 0.001) that was partly explained by differences in age stratification and study area. In addition, subgroup analysis showed that a serum Mg concentration of ≤1.1 mmol/L might be the vigilant cutoff value. Conclusion: A lower serum Mg level was associated with higher all-cause mortality and cardiovascular mortality in patients receiving hemodialysis.

Download Full-text

Therapeutic outcome and related predictors of stereotactic body radiotherapy for small liver-confined HCC: a systematic review and meta-analysis of observational studies

Radiation Oncology ◽

10.1186/s13014-021-01761-1 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Yanyan Long ◽

Yan Liang ◽

Shujie Li ◽

Jing Guo ◽

Ying Wang ◽

...

Keyword(s):

Treatment Outcome ◽

Radiation Dose ◽

Tumor Size ◽

Stereotactic Body Radiotherapy ◽

Observational Studies ◽

Meta Analysis ◽

Local Treatment ◽

Cochrane Library ◽

Tumor Control ◽

Comparison Results

Abstract Background and purpose Stereotactic body radiotherapy (SBRT) is a promising ablative modality for hepatocellular carcinoma (HCC) especially for those with small-sized or early-stage tumors. This study aimed to synthesize available data to evaluate efficacy and explore related predictors of SBRT for small liver-confined HCC (≤ 3 lesions with longest diameter ≤ 6 cm). Materials and methods A systematic search were performed of the PubMed and Cochrane Library databases. Primary endpoints were overall survival (OS) and local control (LC) of small HCC treated with SBRT, meanwhile, to evaluate clinical parameters associated with treatment outcome by two methods including subgroup comparisons and pooled HR meta-analysis. The secondary endpoint was treatment toxicity. Results After a comprehensive database review, 14 observational studies with 1238 HCC patients received SBRT were included. Pooled 1-year and 3-year OS rates were 93.0% (95% confidence interval [CI] 88.0–96.0%) and 72.0% (95% CI 62.0–79.0%), respectively. Pooled 1-year and 3-year LC rates were 96.0% (95% CI 91.0–98.0%) and 91.0% (95% CI 85.0–95.0%), respectively. Subgroup comparisons regarding Child–Pugh class (stratified by CP-A percentage 100%, 75–100%, 50–75%) showed there were statistically significant differences for both 1-year and 3-year OS rate (p < 0.01), while that regarding number of lesions, pretreatment situation, age (median/mean age of 65), macrovascular invasion, tumor size, and radiation dose (median BED10 of 100 Gy), there were no differences. In subgroup comparisons for LC rate, it showed number of lesions (1 lesion vs. 2–3 lesions) was significantly associated with 1-year LC rate (p = 0.04), though not associated with 3-year LC rate (p = 0.72). In subgroup comparisons categorized by other factors including pretreatment situation, age, CP-A percentage, macrovascular invasion, tumor size, and radiation dose, there were no significant differences for 1- or 3-year LC rate. To further explore the association between CP class and OS, the second method was applied by combining HR and 95% CIs. Results indicated CP-A was predictive of better OS (p = 0.001) with pooled HR 0.31 (95% CIs 0.11–0.88), which was consistent with subgroup comparison results. Concerning adverse effect of SBRT, pooled rates of grade ≥ 3 hepatic complications and RILD were 4.0% (95% CI 2.0–8.0%) and 14.7% (95% CI 7.4–24.7%), respectively. Conclusion The study showed that SBRT was a potent local treatment for small liver-confined HCC conferring excellent OS and LC persisting up to 3 years, even though parts of included patients were pretreated or with macrovascular invasion. CP-A class was a significant predictor of optimal OS, while number of lesions might affect short term tumor control (1-year LC). Tumor size and radiation dose were not vital factors impacting treatment outcome for such small-sized HCC patients. Because of the low quality of observational studies and heterogeneous groups of patients treated with SBRT, further clinical trials should be prospectively investigated in large sample sizes.

Download Full-text

Intraosseous versus intravenous vascular access during cardiopulmonary resuscitation for out-of-hospital cardiac arrest: a systematic review and meta-analysis of observational studies

Scandinavian Journal of Trauma Resuscitation and Emergency Medicine ◽

10.1186/s13049-021-00858-6 ◽

2021 ◽

Vol 29 (1) ◽

Author(s):

Yu-Lin Hsieh ◽

Meng-Che Wu ◽

Jon Wolfshohl ◽

James d’Etienne ◽

Chien-Hua Huang ◽

...

Keyword(s):

Cardiac Arrest ◽

Cardiopulmonary Resuscitation ◽

Hospital Discharge ◽

Vascular Access ◽

Subgroup Analysis ◽

Observational Studies ◽

Primary Outcome ◽

Meta Analysis ◽

Cochrane Library ◽

Hospital Cardiac Arrest

Abstract Introduction This study is aimed to investigate the association of intraosseous (IO) versus intravenous (IV) route during cardiopulmonary resuscitation (CPR) with outcomes after out-of-hospital cardiac arrest (OHCA). Methods We systematically searched PubMed, Embase, Cochrane Library and Web of Science from the database inception through April 2020. Our search strings included designed keywords for two concepts, i.e. vascular access and cardiac arrest. There were no limitations implemented in the search strategy. We selected studies comparing IO versus IV access in neurological or survival outcomes after OHCA. Favourable neurological outcome at hospital discharge was pre-specified as the primary outcome. We pooled the effect estimates in random-effects models and quantified the heterogeneity by the I2 statistics. Time to intervention, defined as time interval from call for emergency medical services to establishing vascular access or administering medications, was hypothesized to be a potential outcome moderator and examined in subgroup analysis with meta-regression. Results Nine retrospective observational studies involving 111,746 adult OHCA patients were included. Most studies were rated as high quality according to Newcastle-Ottawa Scale. The pooled results demonstrated no significant association between types of vascular access and the primary outcome (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.27–1.33; I2, 95%). In subgroup analysis, time to intervention was noted to be positively associated with the pooled OR of achieving the primary outcome (OR: 3.95, 95% CI, 1.42–11.02, p: 0.02). That is, when the studies not accounting for the variable of “time to intervention” in the statistical analysis were pooled together, the meta-analytic results between IO access and favourable outcomes would be biased toward inverse association. No obvious publication bias was detected by the funnel plot. Conclusions The meta-analysis revealed no significant association between types of vascular access and neurological outcomes at hospital discharge among OHCA patients. Time to intervention was identified to be an important outcome moderator in this meta-analysis of observation studies. These results call for the need for future clinical trials to investigate the unbiased effect of IO use on OHCA CPR.

Download Full-text

Systematic literature review and network Meta-analysis of sulodexide and other drugs in chronic venous disease

Phlebology The Journal of Venous Disease ◽

10.1177/02683555211015020 ◽

2021 ◽

pp. 026835552110150

Author(s):

Giuseppe Pompilio ◽

Andrew Nicolaides ◽

Stavros K Kakkos ◽

Davide Integlia

Keyword(s):

Ulcer Healing ◽

Observational Studies ◽

Meta Analysis ◽

Relative Effectiveness ◽

Lower Leg ◽

Chronic Venous Disease ◽

Cochrane Library ◽

Horse Chestnut ◽

Venous Disease ◽

Calcium Dobesilate

Objective To assess the clinical efficacy of sulodexide, including a comparison with venoactive drugs (VAD) (micronized purified flavonoid fraction, MPFF; hydroxy-ethyl-rutosides, HR; calcium dobesilate;Ruscus extract combined with hesperidin methyl chalcone and vitamin C, Ruscus+HMC+VitC; horse chestnut seed extract, HCSE) and pentoxifylline in patients with chronic venous disease. Methods We performed a literature search in MEDLINE, Embase, and Cochrane Library for randomized controlled trials (RCTs) and observational studies. Proportion of patients with complete venous ulcer healing was the primary outcome and lower leg volume, foot volume, ankle circumference and symptoms were the secondary outcomes. Bayesian network meta-analysis (NMA) was perfomed with random effects models using only RCTs. A meta-analysis of observational studies was performed for sulodexide because no RCT could be included in NMA for symptoms or signs. Results Forty-five RCTs and eighteen observational studies were identified. Sulodexide was included only in a single NMA for the proportion of patients with complete ulcer healing and it showed to have the highest probability of being the best treatment (48%) compared with pentoxifylline (37%) and MPFF (16%). MPFF was the most effective treatment in reducing lower leg volume, CIVIQ-20 score and pain VAS scale while calcium dobesilate and Ruscus+HMC+VitC were the most effective in reducing foot volume and ankle circumference respectively. Meta-analyses of observational studies for sulodexide showed that it improves significantly the scoring of pain, feeling of swelling, heaviness and parasthesiae measured by Likert scales. Conclusions Sulodexide is at least as effective as pentoxifylline and more effective than MPFF in improving the rate of ulcer healing in patients with CVD. VADs are effective in improving venous symptoms and signs, as was also shown by sulodexide in the meta-analysis of observational studies. The relative effectiveness of sulodexide and VADs needs to be evaluated by an RCT in order to better inform clinical practice.

Download Full-text

Abstract P111: Comparative Efficacy Of Bisoprolol Compared To Other Selective Beta-1 Blockers In Patients With Hypertension - A Systematic Review And Meta-analysis Of Observational Studies

Hypertension ◽

10.1161/hyp.78.suppl_1.p111 ◽

2021 ◽

Vol 78 (Suppl_1) ◽

Author(s):

Uday M Jadhav ◽

Tiny Nair ◽

SANDEEP BANSAL ◽

Saumitra Ray

Keyword(s):

Lipid Profile ◽

Observational Studies ◽

Clinical Decision Making ◽

Meta Analysis ◽

Hdl Cholesterol ◽

Clinical Decision ◽

Cochrane Library ◽

Favourable Effect ◽

Pooled Data ◽

Cholesterol Levels

Introduction: Selective beta-1 blockers (s-BBs) are used in the management of hypertension (HT) in specific subsets. Studies comparing the potency of blood pressure (BP) lowering with different s-BBs are sparse. The objective of this meta-analysis was to evaluate the efficacy of bisoprolol compared to other s-BBs (Atenolol, Betaxolol, Esmolol, Acebutolol, Metoprolol, Nebivolol) in HT patients by examining their effect on BP, heart rate (HR) and metabolic derangements, by examining the evidences reported in observational studies. Methods: Electronic databases like PubMed, EMBASE, Cochrane Library, Clinicaltrials.gov, Surveillance, Epidemiology and End Results Program and 12 PV databases were systematically searched from inception to October 2019. Observational studies that compared bisoprolol with other s-BBs in patients with HT were evaluated in accordance with the PRISMA guidelines. Pooled data were calculated using random-effects model for meta-analysis in terms of mean difference (MD) and 95% confidence interval (95% CI) for each outcome. Outcomes of interest were BP, HR and lipid profile. Results: Four observational studies which compared bisoprolol with other s-BBs (nebivolol and atenolol) were included in this meta-analysis. Significant reduction was observed in office diastolic BP [MD: -1.70; 95% CI: -2.68,-0.72; P <0.01] among arterial HT patients treated with bisoprolol for 26 weeks (w) compared to those treated with other s-BBs. HT patients treated with bisoprolol for 26 w showed significant reduction in HR [MD: -2.20; 95% CI: -3.57,-0.65; P <0.01] and office HR [MD: -2.55; 95% CI: -3.57,-1.53; P <0.01] than other s-BBs. HDL cholesterol levels increased significantly in essential HT patients treated with bisoprolol at 26 w [MD: 7.17; 95% CI: 1.90,12.45; P <0.01], 78 w [MD: 11.70; 95% CI: 4.49,18.91; P <0.01] and 104 w [MD: 10.20, 95% CI: 4.49,18.91; P <0.01] compared to other s-BBs. Conclusion: Our results suggests that bisoprolol is superior to other s-BBs in reducing BP and HR. Bisoprolol also had a favourable effect on lipid profile shown by increase in HDL cholesterol. This meta-analysis emphasizes the efficacy of bisoprolol over other s-BBs, which aids clinical decision making in treatment of patients with HT.

Download Full-text

Physiotherapy and Pelvic Floor Muscle Exercises for the Prevention and Treatment of Pregnancy-Related Pelvic Floor Dysfunctions: A Systematic Review and Meta-analysis

International Journal of Women s Health and Reproduction Sciences ◽

10.15296/ijwhr.2020.20 ◽

2019 ◽

Vol 8 (2) ◽

pp. 125-132

Author(s):

Fahime Khorasani ◽

Fariba Ghaderi ◽

Parvin Sarbakhsh ◽

Parisa Ahadi ◽

Elahe Khorasani ◽

...

Keyword(s):

Systematic Review ◽

Pelvic Floor ◽

Pelvic Floor Muscle ◽

Meta Analysis ◽

Cochrane Library ◽

Control Groups ◽

Pelvic Floor Muscle Exercises ◽

Significant Difference ◽

Prevention And Treatment ◽

Pfm Strength

Objectives: The present systematic review focused on the prevention or treatment of three main types of pelvic floor dysfunctions (PFDs) specifically pelvic organ prolapse (POP), urinary incontinence (UI), and fecal incontinence (FI) using physiotherapy and pelvic floor muscle exercises (PFMEs). With regard to the breadth of the problem, there is not much evidence grounded on the best management. The main purpose of this systematic review was to evaluate the effects of physiotherapy and PFMEs on the prevention and treatment of pregnancy-related PFDs; namely, POP, FI, and UI. Therefore, this review incorporated studies comparing the use of physiotherapy and PFMEs with every other existing interventions. Methods: This systematic review and meta-analysis was conducted on randomized-controlled-trial (RCT) articles and quasi-RCT designs through a search in the studies published with no time limits until December 2017 in the databases of PubMed (Medline), Web of Science, Scopus, Embase, Cochrane Library, and ProQuest. The meta-analysis was also applied for data synthesis. Moreover, heterogeneity was assessed using Cochran’s Q test and I2 index. Results: A total number of 26 RCTs were examined in this review in which the outcome variables were related to POP, UI, and FI prevalence; POP, UI, and FI severity, as well as pelvic floor muscle (PFM) strength and endurance. In most articles, UI prevalence or severity in intervention groups had significantly improved compared with those in controls. The number of studies examining POP and FI was also relatively low. In two studies, FI severity or prevalence in intervention groups had significantly enhanced in comparison with those in control groups; however, FI prevalence in two articles had been reported lower in intervention groups than that in control groups although no significant difference had been observed. There was also no significant improvement in intervention groups in two other studies in this respect. Besides, three articles had not reported traces of improvement in POP, as well as a significant difference between intervention and control groups. Nevertheless, two studies had found a significant improvement in POP in this regard. Based on meta-analysis results for the variable of PFM strength, Cochran’s Q test (P<0.001) and I2 index (90.02) indicated heterogeneity between studies; so, a random-effect meta-analysis was applied to estimate overall effect sizes. The overall mean differences following intervention between the study groups were also equal to 6.94, with a 95% CI (1.36 to 12.52). Conclusions: It was concluded that physiotherapy and PFMEs might have effects on pregnancy-related UI, but they had not consistently reduced FI severity or prevalence and failed to constantly improve POP.

Download Full-text

The effect of eye protection on SARS-CoV-2 transmission: a systematic review

10.1101/2021.08.08.21261770 ◽

2021 ◽

Author(s):

Oyungerel Byambasuren ◽

Elaine Beller ◽

Justin Clark ◽

Peter Collignon ◽

Paul Glasziou

Keyword(s):

Observational Studies ◽

Healthcare Workers ◽

Meta Analysis ◽

Cochrane Library ◽

Eye Protection ◽

Before And After ◽

Retrospective Cohort Studies ◽

The One ◽

General Populations ◽

The Cochrane Library

Background: The effect of eye protection to prevent SARS-CoV-2 infection in the real-world remains uncertain. We aimed to synthesize all available research on the potential impact of eye protection on transmission of SARS-CoV-2. Methods: We searched PROSPERO, PubMed, Embase, The Cochrane Library for clinical trials and comparative observational studies in CENTRAL, and Europe PMC for pre-prints. We included studies that reported sufficient data to estimate the effect of any form of eye protection including face shields and variants, goggles, and glasses, on subsequent confirmed infection with SARS-CoV-2. Findings: We screened 898 articles and included 6 reports of 5 observational studies from 4 countries (USA, India, Columbia, and United Kingdom) that tested face shields, googles and wraparound eyewear on 7567 healthcare workers. The three before-and-after and one retrospective cohort studies showed statistically significant and substantial reductions in SARS-CoV-2 infections favouring eye protection with odds ratios ranging from 0.04 to 0.6, corresponding to relative risk reductions of 96% to 40%. These reductions were not explained by changes in the community rates. However, the one case-control study reported odds ratio favouring no eye protection (OR 1.7, 95% CI 0.99, 3.0). The high heterogeneity between studies precluded any meaningful meta-analysis. None of the studies adjusted for potential confounders such as other protective behaviours, thus increasing the risk of bias, and decreasing the certainty of evidence to very low. Interpretation: Current studies suggest that eye protection may play a role in prevention of SARS-CoV-2 infection in healthcare workers. However, robust comparative trials are needed to clearly determine effectiveness of eye protections and wearability issues in both healthcare and general populations.

Download Full-text

The association of fracture risk in atrial fibrillation patients and long-term anticoagulant therapy category: a systematic review and meta-analysis

PeerJ ◽

10.7717/peerj.10683 ◽

2021 ◽

Vol 9 ◽

pp. e10683

Author(s):

Jun Chen ◽

Lingchun Lyu ◽

Jiayi Shen ◽

Chunlai Zeng ◽

Cheng Chen ◽

...

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Hip Fracture ◽

Fracture Risk ◽

Hip Fractures ◽

Observational Studies ◽

Meta Analysis ◽

Cochrane Library ◽

Hip Fracture Risk ◽

Significant Difference

Objective Our study aimed to assess the risk of all fractures and hip fractures in patients with atrial fibrillation (AF) who took non-vitamin K antagonist oral anticoagulants (NOACs) compared to warfarin. Methods We searched PubMed, Embase, and Cochrane Library and Clinical Trials.gov Website. Reviewed related researches up to January 31, 2020, to identify studies with more than 12 months of follow-up data. The protocol for this systematic review and meta-analysis has been registered in the International Prospective Register of Systematic Reviews (PROSPERO Number: CRD42020156893). Results We included five RCT studies, and five observational studies that contained a total of 326,846 patients in our meta-analysis. Our meta-analysis showed that patients taken NOACs had no significant all fracture risk (RR = 0.91, 95% CI [0.81–1.01]) and hip fracture risk (RR = 0.92, 95% CI [0.82–1.03]) compared with those taken warfarin. Subanalysis showed that the risk of all fractures and hip fractures treated by NOACs were significant lower compared with warfarin in observational studies compared with RCT studies. Also, a subanalysis across the duration of anticoagulation showed the NOACs users have lower all fracture risk than warfarin users when the duration of anticoagulation ≤2 years (RR = 0.89, 95% CI [0.80–0.99]). Further analysis, significant lower all fracture risk in the rivaroxaban therapy (RR = 0.81; 95% CI [0.76–0.86]) compared with warfarin but no statistical significance in hip fracture. There were no significant difference of all fracture risk and hip fracture risk in dabigatran, apixaban, and edoxaban therapy compared with warfarin. Conclusion The meta-analysis demonstrated that NOACs associated with a significantly lower all fracture risk compared with warfarin when the duration of anticoagulation more than 2 years. Rivaroxaban users had lower risk of all fracture than warfarin users in AF patients. But there was no evidence to verify apixaban, edoxaban, and dabigatranin could decrease all fracture and hip fracture risk compared with warfarin.

Download Full-text

Associations Between the Use of Renin–Angiotensin System Inhibitors and the Risks of Severe COVID-19 and Mortality in COVID-19 Patients With Hypertension: A Meta-Analysis of Observational Studies

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.609857 ◽

2021 ◽

Vol 8 ◽

Author(s):

Xiao-Ce Dai ◽

Zhuo-Yu An ◽

Zi-Yang Wang ◽

Zi-Zhen Wang ◽

Yi-Ren Wang

Keyword(s):

Angiotensin Converting Enzyme ◽

Observational Studies ◽

Meta Analysis ◽

Severe Disease ◽

Host Cells ◽

Cochrane Library ◽

Converting Enzyme ◽

Significant Difference ◽

Duration Of Hospitalization ◽

The Impact

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) share a target receptor with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The use of ACEIs/ARBs may cause angiotensin-converting enzyme 2 receptor upregulation, facilitating the entry of SARS-CoV-2 into host cells. There is concern that the use of ACEIs/ARBs could increase the risks of severe COVID-19 and mortality. The impact of discontinuing these drugs in patients with COVID-19 remains uncertain. We aimed to assess the association between the use of ACEIs/ARBs and the risks of mortality and severe disease in patients with COVID-19. A systematic search was performed in PubMed, EMBASE, Cochrane Library, and MedRxiv.org from December 1, 2019, to June 20, 2020. We also identified additional citations by manually searching the reference lists of eligible articles. Forty-two observational studies including 63,893 participants were included. We found that the use of ACEIs/ARBs was not significantly associated with a reduction in the relative risk of all-cause mortality [odds ratio (OR) = 0.87, 95% confidence interval (95% CI) = 0.75–1.00; I2 = 57%, p = 0.05]. We found no significant reduction in the risk of severe disease in the ACEI subgroup (OR = 0.95, 95% CI = 0.88–1.02, I2 = 50%, p = 0.18), the ARB subgroup (OR = 1.03, 95% CI = 0.94–1.13, I2 = 62%, p = 0.48), or the ACEI/ARB subgroup (OR = 0.83, 95% CI = 0.65–1.08, I2 = 67%, p = 0.16). Moreover, seven studies showed no significant difference in the duration of hospitalization between the two groups (mean difference = 0.33, 95% CI = −1.75 to 2.40, p = 0.76). In conclusion, the use of ACEIs/ARBs appears to not have a significant effect on mortality, disease severity, or duration of hospitalization in COVID-19 patients. On the basis of the findings of this meta-analysis, there is no support for the cessation of treatment with ACEIs or ARBs in patients with COVID-19.

Download Full-text