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Chloroquine and hydroxychloroquine are associated with reduced cardiovascular risk: a systematic review and meta-analysis.

ABSTRACT: Background and aims:Chloroquine (CQ) and hydroxychloroquine (HCQ) are widely used in patients with rheumatic diseases, but their effects on the cardiovascular system remain unclear. We aimed to assess whether CQ/HCQ could reduce the risk of cardiovascular disease (CVD). Materials and methods:We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, and the ClinicalTrials.gov for studies investigating the association between CQ/HCQ and the risk of CVD from inception to 20 December 2017. We carried out the quality assessment using the Newcastle-Ottawa Quality Assessment Scale (NOS). Random-effects model was used to pool the risk estimates relative ratio (RR), hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) for the outcomes. Results:A total of 19 studies (7 case-control studies, 12 cohort studies, and no clinical trials) involving 19,679 participants were included in the meta-analysis. Pooled results for HRs or RRs showed that CQ/HCQ was associated with a significantly reduced risk of CVD (pooled RR 0.72, 95% CI 0.56-0.94, p=0.013). Results based on ORs showed a similar tendency towards a reduced risk of CVD with CQ/HCQ (pooled OR 0.41, 95% CI 0.25-0.69, p=0.001). Conclusion:Our results suggested that CQ/HCQ was associated with a reduced risk of CVD in patients with rheumatic diseases. Randomized trials are needed to confirm the potential of CQ/HCQ in cardiovascular prevention in patients with and without rheumatic diseases.

SUBMITTER: Liu D

PROVIDER: S-EPMC6001837 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Chloroquine and hydroxychloroquine are associated with reduced cardiovascular risk: a systematic review and meta-analysis.

Liu Dan D Li Xiaodan X Zhang Yonggang Y Kwong Joey Sum-Wing JS Li Ling L Zhang Yiyi Y Xu Chang C Li Qianrui Q Sun Xin X Tian Haoming H Li Sheyu S

Drug design, development and therapy 20180611

<h4>Background and aims</h4>Chloroquine (CQ) and hydroxychloroquine (HCQ) are widely used in patients with rheumatic diseases, but their effects on the cardiovascular system remain unclear. We aimed to assess whether CQ/HCQ could reduce the risk of cardiovascular disease (CVD).<h4>Materials and methods</h4>We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, and the ClinicalTrials.gov for studies investigating the association between CQ/HCQ and the risk of CV ...[more]

PMID: 29928112

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Project description:Background:Chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have recently emerged as potential antiviral and immunomodulatory options for the treatment of 2019 coronavirus disease (COVID-19). To examine the safety profiles of these medications, we systematically evaluated the adverse events (AEs) of these medications from published randomized controlled trials (RCTs). Methods:We systematically searched MEDLINE, the Cochrane library, the Cochrane Central Register of Controlled Trials (CENTRAL), and the ClinicalTrials.gov for all the RCTs comparing CQ or HCQ with placebo or other active agents, published before June 20, 2020. The random-effects or fixed-effects models were used to pool the risk estimates relative ratio (RR) with 95% confidence interval (CI) for the outcomes. Results:The literature search yielded 23 and 19 studies for CQ and HCQ, respectively, that satisfied our inclusion criteria. Of these studies, we performed meta-analysis on 6 studies for CQ and 18 studies for HCQ. We did not limit our analysis to published records involving viral treatment alone; data also included the usage of either CQ or HCQ for the treatment of other diseases. The trials for the CQ consisted of a total of 2,137 participants (n = 1,077 CQ, n = 1,060 placebo), while the trials for HCQ involved 2,675 participants (n = 1,345 HCQ and n = 1,330 control). The overall mild and total AEs were significantly higher in CQ-treated non-COVID-19 patients, HCQ-treated non-COVID-19 patients, and HCQ-treated COVID-19 patients. The AEs were further categorized into four groups and analyses revealed that neurologic, gastrointestinal (GI), dermatologic, and sensory AEs were higher in participants taking CQ compared to placebo, while GI, dermatologic, sensory, and cardiovascular AEs were higher in HCQ-treated COVID-19 patients compared to control patients. Moreover, subgroup analysis suggested higher AEs with respect to dosage and duration in HCQ group. Data were acquired from studies with perceived low risk of bias, so plausible bias is unlikely to seriously affect the main findings of the current study. Conclusions:Taken together, we found that participants taking either CQ or HCQ exhibited more AEs than participants taking placebo or control. Precautionary measures should be taken when using these drugs to treat COVID-19. The meta-analysis was registered on OSF (https://osf.io/jm3d9). Registration:The meta-analysis was registered on OSF (https://osf.io/jm3d9).

Project description:Repurposed drugs like hydroxycloroquine (HCQ) and chloroquine (CQ) are being tested for potential therapeutic role in COVID-19. We aimed to evaluate efficacy and safety of HCQ and CQ in COVID-19. Using PubMed, EMBASE, medRxiv, Google Scholar, clinicaltrials.gov, electronic search was carried out to identify relevant articles till June 2020 with re-evaluation in last week of November 2020. Observational and interventional clinical studies comparing efficacy of CQ or HCQ to standard management or other drug/s for SARS-CoV-2 infection patients were included. Cochrane review manager version 5.3 was used for synthesis of meta-analysis results. For randomized controlled trials, risk of bias was assessed using Cochrane Collaboration risk of bias assessment tool, version 2.0 (ROB-2). ROBINS-I was used for quality assessment of observational studies. Overall evidence quality generated by review was graded as per GRADE Recommendation. A total of 903 studies were screened. Nineteen studies were included in synthesis of meta-analysis with total of 4,693, 1,626, and 6,491 patients in HCQ/CQ, HCQ/CQ + AZ and control groups, respectively. HCQ/CQ treatment was associated with significantly increased rates of virological cure (OR = 2.08, 95%CI = 1.36-3.17; P = 0.0007) and radiological cure (OR = 3.89, 95%CI = 1.35 - 11.23; P = 0.01) compared to control. HCQ/CQ had no difference in unadjusted mortality rate (unadjusted OR = 0.98 95% CI = 0.70-1.37, P = 0.89, random effect model) and adjusted hazard ratio for mortality (adjusted HR = 1.05, 95%CI = 0.86--1.29; P = 0.64). However, a significant increase in odds of disease progression (OR = 1.77, 95%CI = 1.46-2.13; P < 0.00001) and QT prolongation (OR = 11.15, 95%CI = 3.95-31.44; P < 0.00001) was noted. The results with HCQ/CQ and azithromycin combination were similar to HCQ/CQ mono-therapy. In the light of contemporary evidence on effectiveness of HCQ/CQ, judicious and monitored use of HCQ/CQ for treatment of COVID-19 patients is recommended in low to middle income countries with emphasis on no mortality benefit. Registration number of Systematic review. Register in PROSPERO database: cRD42020187710.

Project description:Cardiovascular adverse events (CVAE) with carfilzomib in patients with multiple myeloma can be potentially life-threatening and remain incompletely characterized. We performed the first systematic review and meta-analysis of carfilzomib-associated CVAE.To determine the incidence of carfilzomib-associated CVAE and to compare the rates of carfilzomib CVAE among different doses and companion therapies.PubMed, EMBASE, Web of Science, and clinicaltrials.gov were queried for the keywords "carfilzomib," "Kyprolis," and "PX-171" through January 1, 2017.Phase 1 to 3 prospective clinical trials of carfilzomib in patients with multiple myeloma with evaluable toxic effects data were eligible for meta-analysis.Data were independently extracted by 2 reviewers following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Pooled incidence rates and relative risks (for randomized trials) and 95% confidence intervals were calculated using a random effects model. Subgroup analyses were performed to assess study-level characteristics associated with CVAE.Cardiovascular adverse events were defined as heart failure, hypertension, ischemia, and arrhythmia. All-grade and grades 3 or higher AEs and study characteristics were recorded.A total of 514 studies were assessed for eligibility. Of those, 24 studies were eligible, including a total of 2594 patients with multiple myeloma. All-grade and grades 3 and higher CVAE were seen in 617 (18.1%) and 274 (8.2%), respectively. Phase 2 or 3 studies and carfilzomib doses of 45 mg/m2 or higher were associated with high-grade CVAE. Median age older than 65 years, prior myeloma therapies, and concurrent myeloma therapies were not associated with CVAE. For the 3 randomized clinical trials, the summary relative risk of all-grade and grade 3 or higher CVAE for patients receiving carfilzomib compared with noncarfilzomib-receiving control patients were 1.8 and 2.2, respectively.Carfilzomib was associated with a significant incidence of CVAE, with higher rates seen with higher doses of carfilzomib. Phase 1 studies may be underdetecting CVAE. Future studies are needed to identify patients at high risk for CVAE, develop optimal monitoring strategies, and explore strategies to mitigate these risks.

Dataset Information

Chloroquine and hydroxychloroquine are associated with reduced cardiovascular risk: a systematic review and meta-analysis.

Publications

Chloroquine and hydroxychloroquine are associated with reduced cardiovascular risk: a systematic review and meta-analysis.

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