Dataset Information

The Association between Sulfonylurea Use and All-Cause and Cardiovascular Mortality: A Meta-Analysis with Trial Sequential Analysis of Randomized Clinical Trials.

ABSTRACT:

Background

Sulfonylureas are an effective and inexpensive treatment for type 2 diabetes. There is conflicting data about the safety of these drugs regarding mortality and cardiovascular outcomes. The objective of the present study was to evaluate the safety of the sulfonylureas most frequently used and to use trial sequential analysis (TSA) to analyze whether the available sample was powered enough to support the results.

Methods and findings

Electronic databases were reviewed from 1946 (Embase) or 1966 (MEDLINE) up to 31 December 2014. Randomized clinical trials (RCTs) of at least 52 wk in duration evaluating second- or third-generation sulfonylureas in the treatment of adults with type 2 diabetes and reporting outcomes of interest were included. Primary outcomes were all-cause and cardiovascular mortality. Additionally, myocardial infarction and stroke events were evaluated. Data were summarized with Peto odds ratios (ORs), and the reliability of the results was evaluated with TSA. Forty-seven RCTs with 37,650 patients and 890 deaths in total were included. Sulfonylureas were not associated with all-cause (OR 1.12 [95% CI 0.96 to 1.30]) or cardiovascular mortality (OR 1.12 [95% CI 0.87 to 1.42]). Sulfonylureas were also not associated with increased risk of myocardial infarction (OR 0.92 [95% CI 0.76 to 1.12]) or stroke (OR 1.16 [95% CI 0.81 to 1.66]). TSA could discard an absolute difference of 0.5% between the treatments, which was considered the minimal clinically significant difference. The major limitation of this review was the inclusion of studies not designed to evaluate safety outcomes.

Conclusions

Sulfonylureas are not associated with increased risk for all-cause mortality, cardiovascular mortality, myocardial infarction, or stroke. Current evidence supports the safety of sulfonylureas; an absolute risk of 0.5% could be firmly discarded.

Review registration

PROSPERO CRD42014004330.

SUBMITTER: Varvaki Rados D

PROVIDER: S-EPMC4829174 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Publications

The Association between Sulfonylurea Use and All-Cause and Cardiovascular Mortality: A Meta-Analysis with Trial Sequential Analysis of Randomized Clinical Trials.

Varvaki Rados Dimitris D Catani Pinto Lana L Reck Remonti Luciana L Bauermann Leitão Cristiane C Gross Jorge Luiz JL

PLoS medicine 20160412 4

<h4>Background</h4>Sulfonylureas are an effective and inexpensive treatment for type 2 diabetes. There is conflicting data about the safety of these drugs regarding mortality and cardiovascular outcomes. The objective of the present study was to evaluate the safety of the sulfonylureas most frequently used and to use trial sequential analysis (TSA) to analyze whether the available sample was powered enough to support the results.<h4>Methods and findings</h4>Electronic databases were reviewed fro ...[more]

PMID: 27071029

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Project description:BackgroundGuidelines recommend metformin as the first-line oral treatment for type 2 diabetes. We conducted a systematic review to assess whether the use of second- and third-generation sulfonylurea agents is associated with benefits and harms in terms of patient-important outcomes compared with metformin.MethodsWe searched several electronic databases and other sources for randomized clinical trials published to August 2011. We included trials that compared sulfonylurea versus metformin monotherapy among patients 18 years or older with type 2 diabetes and that had an intervention period of at least 24 weeks. We assessed risk of bias and extracted data related to interventions and outcomes. The risk of random errors was assessed by trial sequential analysis.ResultsWe included 14 trials (4560 participants). All trials were judged to be at high risk of bias. Data on patient-important outcomes were sparse. Compared with metformin, sulfonylurea did not significantly affect all-cause mortality (relative risk [RR] 0.98, 95% confidence interval [CI] 0.61 to 1.58) or cardiovascular mortality (RR 1.47, 95% CI 0.54 to 4.01). Sulfonylurea significantly decreased the risk of nonfatal macrovascular outcomes (RR 0.67, 95% CI 0.48 to 0.93). However, the definition of this outcome varied among trials, and trial sequential analysis showed that more trials are needed before reliable conclusions can be drawn. No differences between sulfonylurea and metformin were found for change in fasting blood glucose level or glycosylated hemoglobin concentration in the random-effects model. Sulfonylurea resulted in greater weight gain compared with metformin, a finding confirmed in the trial sequential analysis. Significantly more patients in the sulfonylurea arm than in the metformin arm had mild hypoglycemia (RR 2.95, 95% CI 2.13 to 4.07) and severe hypoglycemia (RR 5.64, 95% CI 1.22 to 26.00).InterpretationSome evidence suggests that, compared with metformin, second- and third-generation sulfonylureas may not affect all-cause or cardiovascular mortality but may decrease the risk of nonfatal macrovascular outcomes among patients with type 2 diabetes. They may also increase the risk of hypoglycemia. In general, the available data were too few and inconsistent to provide firm evidence concerning patient-important outcomes in relation to the benefits and harms of sulfonylurea versus metformin monotherapy.

Project description:ImportanceMortality is a common outcome in trials comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG). Controversy exists regarding whether all-cause mortality or cardiac mortality is preferred as a study end point, because noncardiac mortality should be unrelated to the treatment.ObjectiveTo evaluate the difference in all-cause and cause-specific mortality in randomized clinical trials (RCTs) comparing PCI with CABG for the treatment of patients with coronary artery disease.Data sourcesMEDLINE (1946 to the present), Embase (1974 to the present), and the Cochrane Library (1992 to the present) databases were searched on November 24, 2019. Reference lists of included articles were also searched, and additional studies were included if appropriate.Study selectionArticles were considered for inclusion if they were in English, were RCTs comparing PCI with drug-eluting or bare-metal stents and CABG for the treatment of coronary artery disease, and reported mortality and/or cause-specific mortality. Trials of PCI involving angioplasty without stenting were excluded. For each included trial, the publication with the longest follow-up duration for each outcome was selected.Data extraction and synthesisFor data extraction, all studies were reviewed by 2 independent investigators, and disagreements were resolved by a third investigator in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline. Data were pooled using fixed- and random-effects models.Main outcomes and measuresThe primary outcomes were all-cause and cause-specific (cardiac vs noncardiac) mortality. Subgroup analyses were performed for PCI trials using drug-eluting vs bare-metal stents and for trials involving patients with left main disease.ResultsTwenty-three unique trials were included involving 13 620 unique patients (6829 undergoing PCI and 6791 undergoing CABG; men, 39.9%-99.0% of study populations; mean age range, 60.0-71.0 years). The weighted mean (SD) follow-up was 5.3 (3.6) years. Compared with CABG, PCI was associated with a higher rate of all-cause (incidence rate ratio, 1.17; 95% CI, 1.05-1.29) and cardiac (incidence rate ratio, 1.24; 95% CI, 1.05-1.45) mortality but also noncardiac mortality (incidence rate ratio, 1.19; 95% CI, 1.00-1.41).Conclusions and relevancePercutaneous coronary intervention was associated with higher all-cause, cardiac, and noncardiac mortality compared with CABG at 5 years. The significantly higher noncardiac mortality associated with PCI suggests that even noncardiac deaths after PCI may be procedure related and supports the use of all-cause mortality as the end point for myocardial revascularization trials.

Dataset Information

The Association between Sulfonylurea Use and All-Cause and Cardiovascular Mortality: A Meta-Analysis with Trial Sequential Analysis of Randomized Clinical Trials.

Background

Methods and findings

Conclusions

Review registration

Publications

The Association between Sulfonylurea Use and All-Cause and Cardiovascular Mortality: A Meta-Analysis with Trial Sequential Analysis of Randomized Clinical Trials.

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