Efficacy of early treatment with hydroxychloroquine in people with mild to moderate COVID-19: A systematic review and meta-analysis

IntroductionNo early treatment intervention for COVID-19 has proven effective to date. We systematically reviewed the efficacy of hydroxychloroquine as early treatment for COVID-19.Material and methodsRandomized controlled trials (RCTs) evaluating hydroxychloroquine for early treatment of COVID-19 were searched in five engines and preprint websites until September 14, 2021. Primary outcomes were hospitalization and all-cause mortality. Secondary outcomes included COVID-19 symptom resolution, viral clearance, and adverse events. Inverse variance random-effects meta-analyses were performed and quality of evidence (QoE) per outcome was assessed with GRADE methods.ResultsFive RCTs (n=1848) were included. The comparator was placebo in four RCTs and usual care in one RCT. The RCTs used hydroxychloroquine total doses between 1,600 and 4,400 mg and had follow up times between 14 and 90 days. Compared to the controls, early treatment with hydroxychloroquine did not reduce hospitalizations (RR 0.80, 95%CI 0.47-1.36, I2=2%, 5 RCTs, low QoE), all-cause mortality (RR 0.77, 95%CI 0.16-3.68, I2=0%, 5 RCTs, very low QoE), symptom resolution (RR 0.94, 95%CI 0.77-1.16, I2=71%, 3 RCTs, low QoE) or viral clearance at 14 days (RR 1.02, 95%CI 0.82-1.27, I2=65%, 2 RCTs, low QoE). There was a higher non-significant increase of adverse events with hydroxychloroquine vs. controls (RR 2.17, 95%CI 0.86-5.45, I2=92%, 5 RCTs, very low QoE).ConclusionsHydroxychloroquine was not efficacious as early treatment for COVID-19 infections in RCTs with low to very low quality of evidence for all outcomes. More RCTs are needed to elucidate the efficacy of hydroxychloroquine as early treatment intervention.

Download Full-text

Acupuncture for post-stroke depression: a systematic review and meta-analysis

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-021-03277-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ran Liu ◽

Kun Zhang ◽

Qiu-yu Tong ◽

Guang-wei Cui ◽

Wen Ma ◽

...

Keyword(s):

Adverse Events ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Quality Of Evidence ◽

Post Stroke ◽

Assessment Development ◽

Significant Difference ◽

Post Stroke Depression ◽

Meta Analyses

Abstract Background Acupuncture for post-stroke depression (PSD) has been evolving, but uncertainty remains. To assess the existing evidence from randomized clinical trials (RCTs) of acupuncture for PSD, we sought to draw conclusions by synthesizing RCTs. Methods An exhaustive literature search was conducted in seven electronic databases from their inception dates to April 19, 2020, to identify systematic reviews (SRs) and meta-analyses (MAs) on this topic. The primary RCTs included in the SRs/MAs were identified. We also conducted a supplementary search for RCTs published from January 1, 2015, to May 12, 2020. Two reviewers extracted data separately and pooled data using RevMan 5.3 software. The quality of evidence was critically appraised with the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system. Results A total of 17 RCTs involving 1402 patients were included. Meta-analysis showed that participants who received a combination of acupuncture and conventional treatments exhibited significantly lower scores on the HAM-D17, HAM-D24 and HAM-D (MD, − 5.08 [95% CI, − 6.48 to − 3.67], I2 = 0%), (MD, − 9.72 [95% CI, − 14.54 to − 4.91], I2 = 65%) and (MD, − 2.72 [95% CI, − 3.61 to − 1.82], respectively) than those who received conventional treatment. However, there was no significant difference in acupuncture versus antidepressants in terms of the 17-item, 24-item and HAM-D scales (MD, − 0.43 [95% CI, − 1.61 to 0.75], I2 = 51%), (MD, − 3.09 [95% CI, − 10.81 to 4.63], I2 = 90%) and (MD, − 1.55 [95% CI, − 4.36 to 1.26], I2 = 95%, respectively). For adverse events, acupuncture was associated with fewer adverse events than antidepressants (RR, 0.16 [95% CI, 0.07 to 0.39], I2 = 35%), but there was no significant difference in the occurrence of adverse events between the combination of acupuncture and conventional treatments versus conventional treatments (RR, 0.63 [95% CI, 0.21 to 1.83], I2 = 38%). The quality of evidence was low to very low due to the substantial heterogeneity among the included studies. Conclusions The current review indicates that acupuncture has greater effect on PSD and better safety profile than antidepressants, but high-quality evidence evaluating acupuncture for PSD is still needed.

Download Full-text

Efficacy and harms of convalescent plasma for treatment of hospitalized COVID-19 patients: a systematic review and meta-analysis

Archives of Medical Science ◽

10.5114/aoms/132492 ◽

2021 ◽

Author(s):

Alejandro Piscoya ◽

Luis Ng-Sueng ◽

Angela Parra del Riego ◽

Renato Cerna-Viacava ◽

Vinay Pasupuleti ◽

...

Keyword(s):

Adverse Events ◽

Clinical Improvement ◽

Meta Analysis ◽

Random Effect ◽

Standard Of Care ◽

Serious Adverse Events ◽

Quality Of Evidence ◽

All Cause Mortality ◽

Grade Methodology

IntroductionWe systematically reviewed benefits and harms of convalescent plasma (CP) in hospitalized COVID-19 patients.Material and methodsRandomized controlled trials (RCTs) and observational studies assessing CP effects on hospitalized, adult COVID-19 patients were searched until November 24, 2020. We assessed risk of bias (RoB) using Cochrane RoB 2.0 and ROBINS-I tools. Inverse variance random effect meta-analyses were performed. Quality of evidence was evaluated using GRADE methodology. Primary outcomes were all-cause mortality, clinical improvement, and adverse events.ResultsFive RCTs (n = 1067) and 6 cohorts (n = 881) were included. Three and 1 RCTs had some concerns and high RoB, respectively; and there was serious RoB in all cohorts. Convalescent plasma did not reduce all-cause mortality in RCTs of severe (RR = 0.60, 95% CI: 0.33–1.10) or moderate (RR = 0.60, 95% CI: 0.09–3.86) COVID-19 vs. standard of care (SOC); CP reduced all-cause mortality vs. SOC in cohorts (RR = 0.66, 95% CI: 0.49–0.91). Convalescent plasma did not reduce invasive ventilation vs. SOC in moderate disease (RR = 0.85, 95% CI: 0.47–1.55). In comparison to placebo + SOC, CP did not affect all-cause mortality (RR = 0.75, 95% CI: 0.48–1.16) or clinical improvement (HR = 1.07, 95% CI: 0.82–1.40) in severe patients. Adverse and serious adverse events were scarce, similar between CP and controls. Quality of evidence was low or very low for most outcomes.ConclusionsIn comparison to SOC or placebo + SOC, CP did not reduce all-cause mortality in RCTs of hospitalized COVID-19 patients. Convalescent plasma did not have an effect on other clinical or safety outcomes. Until now there is no good quality evidence to recommend CP for hospitalized COVID-19 patients.

Download Full-text

Association of Consumption of Sugar-Sweetened Beverages or Artificially Sweetened Beverages with Mortality: A Systematic Review and Dose–Response Meta-Analysis of Prospective Cohort Studies

Advances in Nutrition ◽

10.1093/advances/nmaa110 ◽

2020 ◽

Author(s):

Yan-Bo Zhang ◽

Yi-Wen Jiang ◽

Jun-Xiang Chen ◽

Peng-Fei Xia ◽

An Pan

Keyword(s):

Meta Analysis ◽

Cochrane Library ◽

Sugar Sweetened Beverage ◽

Quality Of Evidence ◽

Sweetened Beverage ◽

Sweetened Beverages ◽

All Cause Mortality ◽

Meta Analyses ◽

Cvd Mortality

ABSTRACT Sugar-sweetened beverage (SSB) and artificially sweetened beverage (ASB) intakes have been reported to be associated with mortality; however, conclusions have been inconsistent. This review synthesized the evidence on the associations of SSB and ASB intakes with mortality from all causes, cardiovascular disease (CVD), and cancer among all populations (including general, diseased, or occupational populations, etc.). PubMed, EMBASE, Web of Science, Cochrane Library, ProQuest, ClinicalTrials.gov, and the International Clinical Trials Registry Platform were searched up to March 2020. Fifteen studies including 17 cohorts were included in meta-analyses. Each serving (12 fluid ounces or 355 mL) increase in daily SSB consumption was associated with higher risks of all-cause (HR: 1.08; 95% CI: 1.04, 1.12; 11 cohorts with 965,851 participants) and CVD (HR: 1.08; 95% CI: 1.04, 1.12; 13 cohorts with 898,005 participants) mortality. The associations of ASB intakes with all-cause and CVD mortality were J-shaped, and HRs (95% CI) across different doses (0, 1, 1.5, 2, and 2.5 servings/d) were 1.00, 1.01 (0.99, 1.03), 1.04 (1.02, 1.07), 1.08 (1.05, 1.11), and 1.13 (1.09, 1.18) for all-cause mortality and 1.00, 1.01 (0.96, 1.07), 1.07 (1.01, 1.13), 1.15 (1.08, 1.23), and 1.25 (1.14, 1.37) for CVD mortality. No significant association was found for cancer mortality. According to the NutriGrade scoring system, the quality of evidence on the associations of SSB intakes with all-cause and CVD mortality was high, and the quality of evidence on other associations was low to moderate. In summary, higher SSB and ASB intakes were associated with higher risks of all-cause mortality and CVD mortality. Given the limited evidence, future studies should further investigate the association between ASB intakes and cause-specific mortality.

Download Full-text

Effectiveness of e-cigarettes in smoking cessation: a systematic review and meta-analysis

European Journal of Public Health ◽

10.1093/eurpub/ckaa166.1226 ◽

2020 ◽

Vol 30 (Supplement_5) ◽

Author(s):

M Oberndorfer ◽

I Grabovac ◽

S Haider ◽

T E Dorner

Keyword(s):

Systematic Review ◽

Smoking Cessation ◽

Meta Analysis ◽

Current Evidence ◽

Promising Alternative ◽

Quality Of Evidence ◽

Different Populations ◽

Meta Analyses

Abstract Background Reports of the effectiveness of e-cigarettes (ECs) for smoking cessation vary across different studies making implementation recommendations hard to attain. We performed a systematic review and meta-analysis to synthesise the current evidence regarding the effectiveness of ECs for smoking cessation. Methods PubMed, PsycInfo and Embase databases were searched for randomized controlled trials comparing nicotine ECs with non-nicotine ECs or with established smoking cessation interventions (nicotine replacement therapy (NRT) and or counselling) published between 01/01/2014 and 01/05/2019. Data from eligible studies were extracted and used for random-effects meta-analyses. Results Our literature review yielded 13190 publications with 10 studies being identified as eligible for systematic review, covering 8362 participants, and 8 for meta-analyses (n = 30 - 6006). Using the last follow-up of eligible studies, the proportion of smokers achieving abstinence was 1.67 [95CI:0.99 - 2.81] times higher in nicotine EC users compared to non-nicotine EC users. The proportion of abstinent smokers was 1.69 [95CI:1.25 - 2.27] times higher in EC users compared to participants receiving NRT. EC users showed a 2.70 [95CI:1.15 - 6.30] times higher proportion of abstinent smokers in comparison to participants solely receiving counselling. Conclusions Our analysis showed modest effects of nicotine-ECs compared to non-nicotine ECs. When compared to NRT or counselling, results suggest that nicotine EC may be more effective for smoking cessation. As ECs also help maintaining routinized behaviour and social aspects of smoking, we hypothesise that this may explain their advantage as a tool for smoking cessation. However, given the small number of included studies, different populations, heterogeneous designs, and the overall moderate to low quality of evidence, it is not possible to offer clear recommendations. More comparable data is needed to strengthen confidence in the quality of evidence. Key messages The number of previous studies assessing the effectiveness of ECs for smoking cessation is limited. Further, comparability of these studies is restricted, weakening the quality of evidence. Although current evidence on the effectiveness of ECs for smoking cessation is inconclusive, our meta-analyses suggest that ECs could be a promising alternative tool in attempts to achieve abstinence.

Download Full-text

The effectiveness of serious games in improving memory among elderly people with cognitive impairment: A systematic review and meta-analysis (Preprint)

10.2196/preprints.35202 ◽

2021 ◽

Author(s):

Alaa Abd-alrazaq ◽

Dari Alhuwail ◽

Eiman Al-Jafar ◽

Arfan Ahmed ◽

Shuja Mohd Reagu ◽

...

Keyword(s):

Systematic Review ◽

Working Memory ◽

Cognitive Impairment ◽

Verbal Memory ◽

Serious Games ◽

Meta Analysis ◽

The Elderly ◽

Quality Of Evidence ◽

Meta Analyses

BACKGROUND Memory, one of the main cognitive functions, is known to decline by age. Serious games have been used for improving memory among the elderly. The effectiveness of serious games in improving memory has been investigated by several systematic reviews; however, they are limited by design and methodological weaknesses. OBJECTIVE This study aims to assess the effectiveness of serious games in improving memory among the elderly with cognitive impairment. METHODS A systematic review of randomized controlled trials (RCTs) was carried out. The search sources included searching 8 databases, screening reference lists of the included studies and relevant reviews, and checking studies that cited the included studies. Two reviewers independently carried out the study selection, data extraction, risk of bias assessment, and quality of evidence appraisal. Extracted data were synthesized using a narrative approach and a statistical approach (i.e., meta-analysis), as appropriate. RESULTS Out of 466 citations retrieved, 18 studies met the eligibility criteria of this review. Of those, 15 RCTs were eventually included in 10 meta-analyses. We found that serious games are more effective than no or passive interventions in improving non-verbal memory (P=0.002) and working memory (P=0.02), but not verbal memory (P=0.13). The review also showed that serious games are more effective than conventional exercises in improving verbal memory (P=0.004), but not for non-verbal memory (P=0.12) and working memory (P=0.49). Serious games were as effective as conventional cognitive activities in improving verbal memory (P=0.07), non-verbal memory (P=0.94), and working memory (P=0.08) among the elderly with cognitive impairment. Lastly, the effect of adaptive serious games on working memory was comparable to non-adaptive serious games (P=0.08). CONCLUSIONS Serious games have the potential to improve verbal, non-verbal, and working memory among elderly people with cognitive impairment. However, our findings should be interpreted cautiously given that most meta-analyses were based on a few studies (≤3) and judged to have a low quality of evidence. Therefore, serious games should be offered as supplemental to existing proven and safe interventions, rather than a complete substitute until further, more robust evidence is available. Future studies should investigate the short and long-term effects of serious games on memory and other cognitive abilities among people from different age groups with or without cognitive impairment.

Download Full-text

Technology-assisted rehabilitation following total knee or hip replacement for people with osteoarthritis: a systematic review and meta-analysis

BMC Musculoskeletal Disorders ◽

10.1186/s12891-019-2900-x ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 8

Author(s):

Xia Wang ◽

David J. Hunter ◽

Giovana Vesentini ◽

Daniel Pozzobon ◽

Manuela L. Ferreira

Keyword(s):

Adverse Events ◽

Usual Care ◽

Meta Analysis ◽

Hospital Readmissions ◽

Functional Mobility ◽

Cochrane Library ◽

Timed Up And Go ◽

Quality Of Evidence ◽

Evaluation Approach

Abstract Background To evaluate the effectiveness and safety of technology-assisted rehabilitation following total hip/knee replacement (THR/TKR). Methods Six electronic databases were searched without language or time restrictions for relevant studies: MEDLINE, EMBASE, Cochrane Library, CINAHL, SPORTDiscus, Physiotherapy Evidence Database (PEDro); from inception to November 7th, 2018. Two reviewers independently applied inclusion criteria to select eligible randomised controlled trials (RCTs) that investigated the effectiveness of technology-based interventions, compared with usual care or no intervention for people undergoing THR/TKR. Two reviewers independently extracted trial details (e.g. patients’ profile, intervention, outcomes, attrition and adverse events). Study methodological quality was assessed using the PEDro scale. Quality of evidence was critically appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. Results We identified 21 eligible studies assessing telerehabilitation, game- or web-based therapy. There were 17 studies (N = 2188) in post-TKR rehabilitation and 4 studies (N = 783) in post-THR rehabilitation. Compared to usual care, technology-based intervention was more effective in reducing pain (mean difference (MD): − 0.25; 95% confidence interval (CI): − 0.48, − 0.02; moderate evidence) and improving function measured with the timed up-and-go test (MD: -7.03; 95% CI: − 11.18, − 2.88) in people undergoing TKR. No between-group differences were observed in rates of hospital readmissions or treatment-related adverse events (AEs) in those studies. Conclusion There is moderate-quality of evidence showed technology-assisted rehabilitation, in particular, telerehabilitation, results in a statistically significant improvement in pain; and low-quality of evidence for the improvement in functional mobility in people undergoing TKR. The effects were however too small to be clinically significant. For THR, there is very limited low-quality evidence shows no significant effects.

Download Full-text

Effectiveness of Electronic Cigarettes in Smoking Cessation: A Systematic Review and Meta-analysis

Nicotine & Tobacco Research ◽

10.1093/ntr/ntaa181 ◽

2020 ◽

Cited By ~ 4

Author(s):

Igor Grabovac ◽

Moritz Oberndorfer ◽

Jismy Fischer ◽

Winfried Wiesinger ◽

Sandra Haider ◽

...

Keyword(s):

Systematic Review ◽

Smoking Cessation ◽

Random Effects ◽

Electronic Cigarettes ◽

Meta Analysis ◽

Current Evidence ◽

Quality Of Evidence ◽

Registration Number ◽

Meta Analyses

Abstract Introduction Reports of the effectiveness of e-cigarettes (ECs) for smoking cessation vary across different studies making implementation recommendations hard to attain. We performed a systematic review and meta-analysis to assess the current evidence regarding effectiveness of ECs for smoking cessation. Methods PubMed, PsycInfo, and Embase databases were searched for randomized controlled trials comparing nicotine ECs with non-nicotine ECs or with established smoking cessation interventions (nicotine replacement therapy [NRT] and or counseling) published between 1 January 2014 and 27 June 2020. Data from eligible studies were extracted and used for random-effects meta-analyses (PROSPERO registration number: CRD42019141414). Results The search yielded 13 950 publications with 12 studies being identified as eligible for systematic review (N = 8362) and 9 studies for random-effects meta-analyses (range: 30–6006 participants). The proportion of smokers achieving abstinence was 1.71 (95 CI: 1.02–2.84) times higher in nicotine EC users compared with non-nicotine EC users. The proportion of abstinent smokers was 1.69 (95 CI: 1.25–2.27) times higher in EC users compared with participants receiving NRT. EC users showed a 2.04 (95 CI: 0.90–4.64) times higher proportion of abstinent smokers in comparison with participants solely receiving counseling. Conclusions Our results suggest that nicotine ECs may be more effective in smoking cessation when compared with placebo ECs or NRT. When compared with counseling alone, nicotine ECs are more effective short term, but its effectiveness appears to diminish with later follow-ups. Given the small number of studies, heterogeneous design, and the overall moderate to low quality of evidence, it is not possible to offer clear recommendations. Implications The results of this study do not allow for a conclusive argument. However, pooling current evidence points toward a potential for ECs as a smoking cessation tool. Though, given the overall quality of evidence, future studies should aim for more clarity in terms of interventions and larger study populations.

Download Full-text

Efficacy and safety of colchicine in COVID-19: a meta-analysis of randomised controlled trials

RMD Open ◽

10.1136/rmdopen-2021-001746 ◽

2021 ◽

Vol 7 (3) ◽

pp. e001746

Author(s):

Kedar Gautambhai Mehta ◽

Tejas Patel ◽

Paragkumar D Chavda ◽

Parvati Patel

Keyword(s):

Adverse Events ◽

Supportive Care ◽

Meta Analysis ◽

Ventilatory Support ◽

Length Of Hospital Stay ◽

Efficacy And Safety ◽

Serious Adverse Events ◽

Quality Of Evidence ◽

Randomised Controlled

BackgroundColchicine, an anti-inflammatory drug is prescribed nowadays for COVID-19. In this meta-analysis, we evaluated efficacy and safety of colchicine in patients with COVID-19.MethodsWe searched databases for randomised controlled studies evaluating efficacy and/or safety of colchicine as compared with supportive care in patients with COVID-19. The efficacy outcomes were mortality, ventilatory support, intensive care unit (ICU) admission and length of hospital stay. The safety outcomes were adverse events, serious adverse events and diarrhoea. A meta-analytical summary was estimated using random effects model through Mantle-Hanzle method. An I2 test was used to assess heterogeneity. The Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used to assess quality of evidence for each outcome.ResultsOut of 69 full texts assessed, 6 studies (16148 patients with COVID-19) were included in meta-analysis. Patients receiving colchicine did not show significant reduction in mortality (risk difference, RD −0.00 (95% CI −0.01 to 0.01), I2=15%), ventilatory support (risk ratio, RR 0.67 (95% CI 0.38 to 1.21), I2=47%), ICU admission (RR 0.49 (95% CI 0.19 to 1.25), I2=34%), length of hospital stay (mean difference: −1.17 (95% CI −3.02 to 0.67), I2=77%) and serious adverse events (RD −0.01 (95% CI −0.02 to 0.00), I2=28%) than those who received supportive care only. Patients receiving colchicine had higher rates of adverse events (RR 1.58 (95% CI 1.07 to 2.33), I2=81%) and diarrhoea (RR 1.93 (95% CI 1.62 to 2.29), I2=0%) than supportive care treated patients. The GRADE quality of evidence was moderate for most outcomes.ConclusionThe moderate quality evidence suggests no benefit of addition of colchicine to the standard care regimen in patients with COVID-19.

Download Full-text

Efficacy and harms of remdesivir for the treatment of COVID-19: a systematic review and meta-analysis

10.1101/2020.05.26.20109595 ◽

2020 ◽

Cited By ~ 1

Author(s):

Alejandro Piscoya ◽

Luis Fernando Ng-Sueng ◽

Angela Parra del Riego ◽

Renato Cerna-Viacava ◽

Vinay Pasupuleti ◽

...

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Clinical Improvement ◽

Meta Analysis ◽

Case Series ◽

Length Of Hospital Stay ◽

Invasive Ventilation ◽

Serious Adverse Events ◽

All Cause Mortality ◽

Meta Analyses

AbstractBackgroundWe evaluated the efficacy and safety of remdesivir for the treatment of COVID-19.MethodsSystematic review in five engines, pre-print webpages and RCT registries until May 22, 2020 for randomized controlled trials (RCTs) and observational studies evaluating remdesivir on confirmed, COVID-19 adults with pneumonia and/or respiratory insufficiency. Primary outcomes were all-cause mortality, clinical improvement or recovery, need for invasive ventilation, and serious adverse events (SAE). Secondary outcomes included length of hospital stay, progression of pneumonia, and adverse events (AE). Inverse variance random effects meta-analyses were performed.ResultsTwo placebo-controlled RCTs (n=1300) and two case series (n=88) were included. All studies used remdesivir 200mg IV the first day and 100mg IV for 9 more days, and followed up until 28 days. Wang et al. RCT was stopped early due to AEs; ACTT-1 was preliminary reported at 15-day follow up. Time to clinical improvement was not decreased in Wang et al. RCT, but median time to recovery was decreased by 4 days in ACTT-1. Remdesivir did not decrease all-cause mortality (RR 0.71, 95%CI 0.39 to 1.28) and need for invasive ventilation at 14 days (RR 0.57, 95%CI 0.23 to 1.42), but had fewer SAEs (RR 0.77, 95%CI 0.63 to 0.94). AEs were similar between remdesivir and placebo arms. Risk of bias ranged from some concerns to high risk in RCTs.InterpretationThere is paucity of adequately powered and fully reported RCTs evaluating effects of remdesivir in adult, hospitalized COVID-19 patients. Remdesivir should not be recommended for the treatment of severe COVID-19.

Download Full-text

Ivabradine added to usual care in patients with heart failure: a systematic review with meta-analysis and trial sequential analysis

BMJ evidence-based medicine ◽

10.1136/bmjebm-2021-111724 ◽

2021 ◽

pp. bmjebm-2021-111724

Author(s):

Mathias Maagaard ◽

Emil Eik Nielsen ◽

Naqash Javaid Sethi ◽

Ning Liang ◽

Si-Hong Yang ◽

...

Keyword(s):

Heart Failure ◽

Adverse Events ◽

Usual Care ◽

Sequential Analysis ◽

Meta Analysis ◽

Risk Of Bias ◽

Trial Sequential Analysis ◽

Serious Adverse Events ◽

All Cause Mortality

ObjectivesTo assess the beneficial and harmful effects of adding ivabradine to usual care in participants with heart failure.DesignA systematic review with meta-analysis and trial sequential analysis.Eligibility criteriaRandomised clinical trials comparing ivabradine and usual care with usual care (with or without) placebo in participants with heart failure.Information sourcesMedline, Embase, CENTRAL, LILACS, CNKI, VIP and other databases and trial registries up until 31 May 2021.Data extractionPrimary outcomes were all-cause mortality, serious adverse events and quality of life. Secondary outcomes were cardiovascular mortality, myocardial infarction and non-serious adverse events. We performed meta-analysis of all outcomes. We used trial sequential analysis to control risks of random errors, the Cochrane risk of bias tool to assess the risks of systematic errors and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of the evidence.ResultsWe included 109 randomised clinical trials with 26 567 participants. Two trials were at low risk of bias, although both trials were sponsored by the company that developed ivabradine. All other trials were at high risk of bias. Meta-analyses and trial sequential analyses showed that we could reject that ivabradine versus control reduced all-cause mortality (risk ratio (RR)=0.94; 95% CI 0.88 to 1.01; p=0.09; high certainty of evidence). Meta-analysis and trial sequential analysis showed that ivabradine seemed to reduce the risk of serious adverse events (RR=0.90; 95% CI 0.87 to 0.94; p<0.00001; number needed to treat (NNT)=26.2; low certainty of evidence). This was primarily due to a decrease in the risk of ‘cardiac failure’ (RR=0.83; 95% CI 0.71 to 0.97; p=0.02; NNT=43.9), ‘hospitalisations’ (RR=0.89; 95% CI 0.85 to 0.94; p<0.0001; NNT=36.4) and ‘ventricular tachycardia’ (RR=0.59; 95% CI 0.43 to 0.82; p=0.001; NNT=212.8). However, the trials did not describe how these outcomes were defined and assessed during follow-up. Meta-analyses showed that ivabradine increased the risk of atrial fibrillation (RR=1.19; 95% CI 1.04 to 1.35; p=0.008; number needed to harm (NNH)=116.3) and bradycardia (RR=3.95; 95% CI 1.88 to 8.29; p=0.0003; NNH=303). Ivabradine seemed to increase quality of life on the Kansas City Cardiomyopathy Questionnaire (KCCQ) (mean difference (MD)=2.92; 95% CI 1.34 to 4.50; p=0.0003; low certainty of evidence), but the effect size was small and possibly without relevance to patients, and on the Minnesota Living With Heart Failure Questionnaire (MLWHFQ) (MD=−5.28; 95% CI −6.60 to −3.96; p<0.00001; very low certainty of evidence), but the effects were uncertain. Meta-analysis showed no evidence of a difference between ivabradine and control when assessing cardiovascular mortality and myocardial infarction. Ivabradine seemed to increase the risk of non-serious adverse events.Conclusion and relevanceHigh certainty evidence shows that ivabradine does not seem to affect the risks of all-cause mortality and cardiovascular mortality. The effects on quality of life were small and possibly without relevance to patients on the KCCQ and were very uncertain for the MLWHFQ. The effects on serious adverse events, myocardial infarction and hospitalisation are uncertain. Ivabradine seems to increase the risk of atrial fibrillation, bradycardia and non-serious adverse events.PROSPERO registration number: CRD42018112082.

Download Full-text