Dataset Information

Allopurinol for Secondary Prevention in Patients with Cardiovascular Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

ABSTRACT:

Background

The effects of allopurinol in patients with cardiovascular disease are not well defined; therefore, the latest evidence is summarized in this study.

Methods

PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for randomized controlled trials (RCTs) of allopurinol in patients with cardiovascular disease published up to 11 February 2023. The primary outcome was cardiovascular death.

Results

We combined the results of 21 RCTs that included 22,806 patients. Compared to placebo/usual care, allopurinol treatment was not associated with a significant reduction in cardiovascular death (RR 0.60; 95% CI 0.33-1.11) or all-cause death (RR 0.90; 95% CI 0.72-1.12). However, evidence from earlier trials and studies with small sample sizes indicated that allopurinol might confer a protective effect in decreasing cardiovascular death (RR 0.34; 95% CI 0.15-0.76) across patients undergoing coronary artery bypass grafting (CABG) or having acute coronary syndrome (ACS). In comparisons between allopurinol and febuxostat, we observed no difference in cardiovascular death (RR 0.92; 95% CI 0.69-1.24) or all-cause death (RR 1.02; 95% CI 0.75-1.38).

Conclusion

Allopurinol could not reduce cardiovascular (CV) death or major adverse CV outcomes significantly in patients with existing cardiovascular diseases. Given the limitations of the original studies, the potential advantages of allopurinol observed in patients undergoing CABG or presenting with ACS necessitate further confirmation through subsequent RCTs. In the comparisons between allopurinol and febuxostat, our analysis failed to uncover any marked superiority of allopurinol in reducing the risk of adverse cardiovascular incidents.

SUBMITTER: Ye Y

PROVIDER: S-EPMC10532321 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Allopurinol for Secondary Prevention in Patients with Cardiovascular Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Ye Yuyang Y Liao Guangzhi G Liu Ting T Hu Xinru X Chen Xuefeng X Bai Lin L Peng Yong Y

Journal of cardiovascular development and disease 20230904 9

<h4>Background</h4>The effects of allopurinol in patients with cardiovascular disease are not well defined; therefore, the latest evidence is summarized in this study.<h4>Methods</h4>PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for randomized controlled trials (RCTs) of allopurinol in patients with cardiovascular disease published up to 11 February 2023. The primary outcome was cardiovascular death.<h4>Results</h4>We combined the results of 21 RCTs that includ ...[more]

PMID: 37754808

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Project description:To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas.We conducted a systematic review and meta-analysis of published studies. We searched PubMed, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the ClinicalTrials.gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes (recurrence of colorectal adenomas, and advanced or "high-risk" adenomas), and rated each trial's risk-of-bias. Between-study heterogeneity was assessed, and pooled risk ratio (RR) estimates with their 95% confidence intervals (95%CI) were calculated using fixed- and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat (NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE.Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas (fixed-effects, RR = 0.89, 95%CI: 0.82-0.96; random-effects, RR = 0.87, 95%CI: 0.77-0.98; high quality of evidence). The NNT was 20 (95%CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance (fixed-effects, RR = 0.92, 95%CI: 0.75-1.13; random-effects, RR = 0.92, 95%CI: 0.71-1.18; moderate quality of evidence).Our results suggest a modest chemopreventive effect of calcium supplements against recurrent colorectal adenomas over a period of 36 to 60 mo. Further research is warranted.

Project description:BackgroundXanthine oxidase inhibitors (XOI), classified as purine-like (allopurinol and oxypurinol) and non-purine (febuxostat and topiroxostat) XOI, present antioxidant properties by reducing the production of reactive oxygen species derived from purine metabolism. Oxidative stress is an important factor related to endothelial dysfunction and ischemia-reperfusion injury, and may be implicated in the pathogenesis of heart failure, hypertension, and ischemic heart disease. However, there is contradictory evidence regarding the possible cardiovascular (CV) protective effect exerted by XOI. Our objective is to compare the incidence of major adverse cardiovascular events (MACE), mortality, total (TCE) and specific CV events in randomized controlled trials (RCTs) testing XOI against placebo or no treatment.MethodsPubMed, EMBASE, Web of Science, Cochrane Central, Lilacs databases were searched from inception to Dec 30 2016, along with hand searching. RCTs including exclusively adult individuals, lasting ≥ 4 weeks, with no language restriction, were eligible. Independent paired researchers selected studies and extracted data. Considering the expected rarity of events, Peto and DerSimonian/Laird odds ratios (OR), the latter in case of heterogeneity, were used for analysis. Random-effects meta-regression was used to explore heterogeneity.ResultsThe analysis of MACE included 81 articles (10,684 patients, 6434 patient-years). XOI did not significantly reduce risk of MACE (ORP = 0.71, 95% CI 0.46-1.09) and death (0.89, 0.59-1.33), but reduced risk of TCE (0.60, 0.44-0.82; serious TCE: 0.64, 0.46 to 0.89), and hypertension (0.54, 0.37 to 0.80). There was protection for MACE in patients with previous ischemic events (0.42, 0.23-0.76). Allopurinol protected for myocardial infarction (0.38, 0.17-0.83), hypertension (0.32, 0.18-0.58), TCE (0.48, 0.31 to 0.75, I2 = 55%) and serious TCE (0.56, 0.36 to 0.86, I2 = 44%). Meta-regression associated increasing dose of allopurinol with higher risk of TCE and serious TCE (P < 0.05). Accordingly, lower doses (≤ 300 mg/day) of allopurinol reduced the risk of TCE, unlike higher doses. Non-purine-like XOI did not significantly reduce or increase the risk of adverse CV events, but confidence intervals were wide. Quality of evidence was generally low to moderate.ConclusionsPurine-like XOI may reduce the incidence of adverse CV outcomes. However, higher doses of allopurinol (> 300 mg/day) may be associated with loss of CV protection.

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Project description:In 2012, the United States Food and Drug Administration (FDA) issued a warning regarding potential adverse effects of HMG-CoA reductase inhibitors (statins) on cognition, based on the Adverse Events Reporting System and a review of the medical literature. We aimed to synthesize randomized clinical trial (RCTs) evidence on the association between statin therapy and cognitive outcomes.We searched MEDLINE, EMBASE, and Cochrane CENTRAL through December 2012, and reviewed published systematic reviews of statin treatment. We sought RCTs that compared statin treatment versus placebo or standard care, and reported at least one cognitive outcome (frequency of adverse cognitive events or measurements using standard neuropsychological cognitive test scores). Studies reporting sufficient information to calculate effect sizes were included in meta-analyses. Standardized and unstandardized mean differences were calculated for continuous outcomes for global cognition and for pre-specified cognitive domains. The main outcome was change in cognition measured by neuropsychological tests; an outcome of secondary interest was the frequency of adverse cognitive events observed during follow-up.We identified 25 RCTs (all placebo-controlled) reporting cognitive outcomes in 46,836 subjects, of which 23 RCTs reported cognitive test results in 29,012 participants. Adverse cognitive outcomes attributable to statins were rarely reported in trials involving cognitively normal or impaired subjects. Furthermore, meta-analysis of cognitive test data (14 studies; 27,643 participants) failed to show significant adverse effects of statins on all tests of cognition in either cognitively normal subjects (standardized mean difference 0.01, 95% confidence interval, CI, -0.01 to 0.03, p?=?0.42) or Alzheimer's disease subjects (standardized mean difference -0.05, 95% CI -0.19 to 0.10, p?=?0.38).Statin therapy was not associated with cognitive impairment in RCTs. These results raise questions regarding the continued merit of the FDA warning about potential adverse effects of statins on cognition.

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Project description:BackgroundThe high prevalence of delirium among postoperative patients has increased morbidity and mortality. The kind of drug that can effectively reduce the incidence of delirium has become the focus of discussion in recent years. However, a consensus in this respect has yet to be reached.MethodsRandomized controlled trials (RCTs) were retrieved from the PubMed, Cochrane Library, ClinicalTrials.gov, and Embase databases from their inception through October 12, 2018. We included RCTs of pharmacological prevention for postoperative delirium in adults (at least 18 years), and the Cochrane risk of bias tool was used to evaluate the methodological quality of trials. The primary outcomes were the risk ratios (RRs) of incidence of postoperative delirium, and the secondary outcomes were the RRs of mortality and adverse events in the intervention and control groups.ResultsThirty-eight trials, which comprised 20302 patients and 18 different drugs, were included in the analysis. Of the 38 studies, 17 were rated as low risk with respect to methodological quality. Dexmedetomidine administration (RR 0.58, 95%CI 0.44-0.76, P<0.01) was associated with a significantly lower incidence of postoperative delirium than the control conditions. However, the findings from the studies with a low risk of bias did not show a significant difference in this beneficial effect (RR 0.64, 95%CI 0.39-1.04, P=0.07). The antipsychotic drugs olanzapine (RR 0.44, 95%CI 0.30- 0.65, P<0.01) and risperidone (RR 0.42, 95%CI 0.19-0.92, P=0.03) had promising effects, but there was a lack of sufficient evidence to obtain a definitive conclusion. The beneficial effect of other drugs, including haloperidol, methylprednisolone, dexamethasone, gabapentin, ketamine, cyproheptadine, donepezil, hypertonic saline, melatonin, nimodipine, ondansetron, pregabalin, rivastigmine, TJ-54, and tryptophan, was not proven on the basis of present evidence.ConclusionAmong the pharmacological prophylactic measures for postoperative delirium, dexmedetomidine, olanzapine, and risperidone showed higher efficacy than other drugs. However, more high-quality evidence is needed to confirm these results.

Dataset Information

Allopurinol for Secondary Prevention in Patients with Cardiovascular Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background

Methods

Results

Conclusion

Publications

Allopurinol for Secondary Prevention in Patients with Cardiovascular Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Similar Datasets

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