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Drugs for treating severe hypertension in pregnancy: a network meta-analysis and trial sequential analysis of randomized clinical trials.

ABSTRACT: AIMS:Several antihypertensive drugs are used in the treatment of severe hypertension in pregnancy. The present study is a network meta-analysis comparing the efficacy and safety of these drugs. METHODS:Electronic databases were searched for randomized clinical trials comparing drugs used in the treatment of severe hypertension in pregnancy. The number of women achieving the target blood pressure (BP) was the primary outcome. Doses required and time taken for achieving the target BP, failure rate, and incidences of maternal tachycardia, palpitation, hypotension, headache, and neonatal death and stillbirth were the secondary outcomes. Mixed treatment comparison pooled estimates were generated using a random-effects model. Odds ratios for the categorical and mean difference for the numerical outcomes were the effect estimates. RESULTS:Fifty-one studies were included in the systematic review and 46 in the meta-analysis. No significant differences in the number of patients achieving target BP was observed between any of the drugs. Diazoxide [-15 (-20.6, -9.4)], nicardipine [-11.8 (-22.3, -1.2)], nifedipine/celastrol [-19.3 (-27.4, -11.1)], nifedipine/vitamin D [-17.1 (-25.7, -9.7)], nifedipine/resveratrol [-13.9 (-22.6, -5.2)] and glyceryl trinitrate [-33.8 (-36.7, -31)] were observed to achieve the target BP (in minutes) more rapidly than hydralazine. Nifedipine required fewer doses than hydralazine for achieving the target BP. Glyceryl trinitrate and labetalol were associated with fewer incidences of tachycardia and palpitation respectively than hydralazine. Trial sequential analysis concluded adequate evidence for hydralazine and nifedipine compared with labetalol. Moderate quality of evidence was observed for direct comparison estimate between labetalol and hydralazine but was either low or very low for other comparisons. CONCLUSION:The present evidence suggests similar efficacy between nifedipine, hydralazine and labetalol in the treatment of severe hypertension in pregnancy. Subtle differences may exist in their safety profile. The evidence is inadequate for other drugs.

SUBMITTER: Sridharan K

PROVIDER: S-EPMC6089822 | biostudies-other | 2018 Sep

REPOSITORIES: biostudies-other

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Drugs for treating severe hypertension in pregnancy: a network meta-analysis and trial sequential analysis of randomized clinical trials.

Sridharan Kannan K Sequeira Reginald P RP

British journal of clinical pharmacology 20180708 9

<h4>Aims</h4>Several antihypertensive drugs are used in the treatment of severe hypertension in pregnancy. The present study is a network meta-analysis comparing the efficacy and safety of these drugs.<h4>Methods</h4>Electronic databases were searched for randomized clinical trials comparing drugs used in the treatment of severe hypertension in pregnancy. The number of women achieving the target blood pressure (BP) was the primary outcome. Doses required and time taken for achieving the target B ...[more]

PMID: 29974489

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Project description:BackgroundPulmonary arterial hypertension (PAH) is a devastating disease and ultimately leads to right heart failure and premature death. A total of four classical targeted drugs, prostanoids, endothelin receptor antagonists (ERAs), phosphodiesterase 5 inhibitors (PDE-5Is), and soluble guanylate cyclase stimulator (sGCS), have been proved to improve exercise capacity and hemodynamics compared to placebo; however, direct head-to-head comparisons of these drugs are lacking. This network meta-analysis was conducted to comprehensively compare the efficacy of these targeted drugs for PAH.MethodsMedline, the Cochrane Library, and other Internet sources were searched for randomized clinical trials exploring the efficacy of targeted drugs for patients with PAH. The primary effective end point of this network meta-analysis was a 6-minute walk distance (6MWD).ResultsThirty-two eligible trials including 6,758 patients were identified. There was a statistically significant improvement in 6MWD, mean pulmonary arterial pressure, pulmonary vascular resistance, and clinical worsening events associated with each of the four targeted drugs compared with placebo. Combination therapy improved 6MWD by 20.94 m (95% confidence interval [CI]: 6.94, 34.94; P=0.003) vs prostanoids, and 16.94 m (95% CI: 4.41, 29.47; P=0.008) vs ERAs. PDE-5Is improved 6MWD by 17.28 m (95% CI: 1.91, 32.65; P=0.028) vs prostanoids, with a similar result with combination therapy. In addition, combination therapy reduced mean pulmonary artery pressure by 3.97 mmHg (95% CI: -6.06, -1.88; P<0.001) vs prostanoids, 8.24 mmHg (95% CI: -10.71, -5.76; P<0.001) vs ERAs, 3.38 mmHg (95% CI: -6.30, -0.47; P=0.023) vs PDE-5Is, and 3.94 mmHg (95% CI: -6.99, -0.88; P=0.012) vs sGCS. There were no significant differences in all-cause mortality and severe adverse events between prostanoids, ERAs, PDE-5Is, sGCS, combination therapy, and placebo.ConclusionAll targeted drugs for PAH are associated with improved clinical outcomes, especially combination therapy. However, all these drugs seem to show less favorable effects on survival in the short-term follow-up, suggesting further clinical trials are required.

Project description:IntroductionDespite the significant morbidity and mortality associated with alcoholic hepatitis, a consensus or generally accepted therapeutic strategy has not yet been reached. The purpose of this analysis was to evaluate the effects of corticosteroids and pentoxifylline on short-term mortality, incidence of hepatorenal syndrome, and sepsis in patients with severe alcoholic hepatitis.Materials and methodsWe conducted a comprehensive search of the Cochrane library, PUBMED, Scopus, EMBASE, and published proceedings from major hepatology and gastrointestinal meetings from January 1970 to June 2015. All relevant articles irrespective of language, year of publication, type of publication, or publication status were included. Two independent reviewers extracted data and scored publications; a third investigator adjudicated discrepancies. The κ scores were measured to assess the agreement between the 2 initial reviewers. The review and meta-analyses were performed following the recommendations of The Cochrane Collaboration. Conventional meta-analysis and Trial sequential analysis were performed. GRADEpro version 3.6 was used to appraise the quality of epidemiologic evidence.ResultsA total of 14 studies satisfied inclusion criteria comparing corticosteroids, pentoxifylline, or placebo. Compared with placebo, corticosteroids reduced 28-day mortality (RR=0.53; 95% CI, 0.33-0.84; P=0.006). There was no statistically significant difference in short-term mortality between pentoxifylline and placebo (RR=0.74; 95% CI, 0.46-1.18; P=0.21). Neither corticosteroids nor pentoxifylline impacted the incidence of hepatorenal syndrome or sepsis. Trial sequential analysis confirmed the results of our conventional meta-analysis.Conclusions and relevanceCorticosteroids demonstrated a decrease in 28-day mortality in patients with severe alcoholic hepatitis. The evidence from this study is insufficient to support any recommendations regarding the mortality benefit of pentoxifylline in severe alcoholic hepatitis.

Project description:BackgroundMany recent studies have investigated the role of drug interventions for coronavirus disease 2019 (COVID-19) infection. However, an important question has been raised about how to select the effective and secure medications for COVID-19 patients. The aim of this analysis was to assess the efficacy and safety of the various medications available for severe and non-severe COVID-19 patients based on randomized placebo-controlled trials (RPCTs).MethodsWe did an updated network meta-analysis. We searched the databases from inception until July 31, 2021, with no language restrictions. We included RPCTs comparing 49 medications and placebo in the treatment of severe and non-severe patients (aged 18 years or older) with COVID-19 infection. We extracted data on the trial and patient characteristics, and the following primary outcomes: all-cause mortality, the ratios of virological cure, and treatment-emergent adverse events. Odds ratio (OR) and their 95% confidence interval (CI) were used as effect estimates.ResultsFrom 3,869 publications, we included 61 articles related to 73 RPCTs (57 in non-severe COVID-19 patients and 16 in severe COVID-19 patients), comprising 20,680 patients. The mean sample size was 160 (interquartile range 96-393) in this study. The median duration of follow-up drugs intervention was 28 days (interquartile range 21-30). For increase in virological cure, we only found that proxalutamide (OR 9.16, 95% CI 3.15-18.30), ivermectin (OR 6.33, 95% CI 1.22-32.86), and low dosage bamlanivimab (OR 5.29, 95% CI 1.12-24.99) seemed to be associated with non-severe COVID-19 patients when compared with placebo, in which proxalutamide seemed to be better than low dosage bamlanivimab (OR 5.69, 95% CI 2.43-17.65). For decrease in all-cause mortality, we found that proxalutamide (OR 0.13, 95% CI 0.09-0.19), imatinib (OR 0.49, 95% CI 0.25-0.96), and baricitinib (OR 0.58, 95% CI 0.42-0.82) seemed to be associated with non-severe COVID-19 patients; however, we only found that immunoglobulin gamma (OR 0.27, 95% CI 0.08-0.89) was related to severe COVID-19 patients when compared with placebo. For change in treatment-emergent adverse events, we only found that sotrovimab (OR 0.21, 95% CI 0.13-0.34) was associated with non-severe COVID-19 patients; however, we did not find any medications that presented a statistical difference when compared with placebo among severe COVID-19 patients.ConclusionWe conclude that marked variations exist in the efficacy and safety of medications between severe and non-severe patients with COVID-19. It seems that monoclonal antibodies (e.g., low dosage bamlanivimab, baricitinib, imatinib, and sotrovimab) are a better choice for treating severe or non-severe COVID-19 patients. Clinical decisions to use preferentially medications should carefully consider the risk-benefit profile based on efficacy and safety of all active interventions in patients with COVID-19 at different levels of infection.

Project description:Background: Severe pneumonia (SP) has a high mortality rate and is responsible for significant healthcare costs. Chinese herbal injections (CHIs) have been widely used in China as a novel and promising treatment option for SP. Therefore, this study assessed and ranked the effectiveness of CHIs to provide more sights for the selection of SP treatment. Method: Seven databases were searched from their inception up to April 1, 2021. The methodological quality of included study was evaluated by the Cochrane risk-of-bias tool. Then, a Bayesian network meta-analysis (NMA) was performed by OpenBUGS 3.2.3 and STATA 14.0 software. The surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the examined treatments. A clustering analysis was utilized to compare the effect of CHIs between two different outcomes. Results: A total of 64 eligible randomized controlled trials (RCTs) involving 5,904 participants were identified for this analysis. Six CHIs including Xuebijing injection (XBJ), Tanreqing injection (TRQ), Reduning injection (RDN), Xiyanping injection (XYP), Shenfu injection (SF), and Shenmai injection (SM) were included. The results of the NMA showed that XBJ [odds ratio (OR) = 0.24, 95% credible interval (CI): 0.19, 0.30], TRQ (OR = 0.22, 95% CI: 0.12, 0.37), RDN (OR = 0.29, 95% CI: 0.04, 0.94), and SM (OR = 0.27, 95% CI: 0.08, 0.63) combined with conventional Western medicine (WM) improved the clinical effective rate more significantly than WM alone. Based on SUCRA values, TRQ + WM (SUCRA: 66.4%) ranked the highest in improving the clinical effective rate, second in four different outcomes, and third in only one. According to the cluster analysis, TRQ + WM exerted a positive effect on improving the efficacy of SP. As for safety, less than 30% (18 RCTs) of the included studies reported adverse drug reactions/adverse drug events (ADRs/ADEs), including 14 RCTs of XBJ, 3 RCTs of TRQ, and 1 RCT of RDN. Conclusion: In conclusion, the study found that the CHIs as co-adjuvant therapy could be beneficial for patients with SP. TRQ + WM showed an outstanding improvement in patients with SP considering both the clinical effective rate and other outcomes. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021244587].

Project description:BackgroundWe aimed to address which antihypertensives are superior to placebo/no therapy or another antihypertensive for controlling nonsevere pregnancy hypertension and provide future sample size estimates for definitive evidence.MethodsRandomized trials of antihypertensives for nonsevere pregnancy hypertension were identified from online electronic databases, to February 28, 2021 (registration URL: https://www.crd.york.ac.uk/PROSPERO/; unique identifier: CRD42020188725). Our outcomes were severe hypertension, proteinuria/preeclampsia, fetal/newborn death, small-for-gestational age infants, preterm birth, and admission to neonatal care. A Bayesian random-effects model generated estimates of direct and indirect treatment comparisons. Trial sequential analysis informed future trials needed.ResultsOf 1246 publications identified, 72 trials were included; 61 (6923 women) were informative. All commonly prescribed antihypertensives (labetalol, other β-blockers, methyldopa, calcium channel blockers, and mixed/multi-drug therapy) versus placebo/no therapy reduced the risk of severe hypertension by 30% to 70%. Labetalol decreased proteinuria/preeclampsia (odds ratio, 0.73 [95% credible interval, 0.54-0.99]) and fetal/newborn death (odds ratio, 0.54 [0.30-0.98]) compared with placebo/no therapy, and proteinuria/preeclampsia compared with methyldopa (odds ratio, 0.66 [0.44-0.99]) and calcium channel blockers (odds ratio, 0.63 [0.41-0.96]). No other differences were identified, but credible intervals were wide. Trial sequential analysis indicated that 2500 to 10 000 women/arm (severe hypertension or safety outcomes) to >15 000/arm (fetal/newborn death) would be required to provide definitive evidence.ConclusionsIn summary, all commonly prescribed antihypertensives in pregnancy reduce the risk of severe hypertension, but labetalol may also decrease proteinuria/preeclampsia and fetal/newborn death. Evidence is lacking for many other safety outcomes. Prohibitive sample sizes are required for definitive evidence. Real-world data are needed to individualize care.

Project description:BackgroundSevere pneumonia (SP) has a high mortality and is responsible for significant healthcare cost. Chinese herbal injections (CHIs) have been widely used in China as a novel and promising treatment option for SP. Therefore, this study will assess and rank the effectiveness of CHIs to provide more sights for the selection of SP treatment.MethodSeven databases will be searched, including PubMed, the Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Database, and the Chinese Scientific Journal Database (VIP) from their inception up to October, 2021. The literatures screening, data extraction and the quality assessment of included studies will be conducted independently by two reviewers. Then Bayesian network meta-analysis (NMA) will be performed by WinBUGS 14.0 and STATA 14.0 software. Surface under the cumulative ranking curve (SUCRA) probability values will be applied to rank the examined treatments. The risk of bias of each included study will be evaluated using the Revised Cochrane risk-of-bias tool for randomized trials (ROB 2). Publication bias will be reflected by a funnel plot.ResultsThe results of this NMA will be disseminated through a peer-reviewed journal publication.ConclusionOur study findings maybe reveal which CHI or CHIs will be better in the treatment of SP and provide more therapy strategies for clinical practitioners and patients.Prospero registration numberCRD42021244587.Strengths and limitations of this studyBayesian network meta-analysis (NMA) can integrate direct evidence with indirect evidence of severe pneumonia treated by Chinese herbal injections to generate a clinically useful ranking of these regimens. This NMA will address Chinese herbal injections for SP and its findings may help to provide more sights for selection of SP treatment. Evidence drawn from an NMA is limited and should be interpreted with caution. We only included studies in Chinese and English languages, which may increase the publication bias.

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Drugs for treating severe hypertension in pregnancy: a network meta-analysis and trial sequential analysis of randomized clinical trials.

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Drugs for treating severe hypertension in pregnancy: a network meta-analysis and trial sequential analysis of randomized clinical trials.

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