Dual antiplatelet therapy following percutaneous coronary intervention: protocol for a systematic review

Abstract

IntroductionDual antiplatelet therapy (DAPT) is routinely given to patients after percutaneous coronary intervention (PCI) with stenting; however, there is ongoing debate about the optimal duration, especially in specific patient groups. In the proposed systematic review, we intend to assess the optimal duration of DAPT following PCI with stenting, with a focus on clinically relevant patient subgroups.Methods and analysisWe will perform a comprehensive search of the published literature for randomised controlled trials (RCTs) assessing the benefits and harms of extended DAPT (>12 months) compared with short-term DAPT (6–12 months) following PCI with stenting (bare metal or drug eluting). ClinicalTrials.gov and ICTRP will also be searched to identify ongoing and completed clinical trials. Two independent reviewers will select studies for inclusion, and the risk of bias will be assessed by use of Cochrane’s Risk of Bias tool. The primary outcome of interest is death (all-cause, cardiovascular, non-cardiovascular). Secondary outcomes are bleeding (major, minor, gastrointestinal), urgent target vessel revascularisation, major adverse cardiovascular events, myocardial infarction, stroke and stent thrombosis. Subgroup data will be sought for patients with prior myocardial infarction, acute coronary syndrome at presentation and diabetes, and based on smoking status and age group. Data will be analysed by random-effects meta-analysis, and separate analyses will be performed for patient subgroups. Bayesian network meta-analysis will be performed to investigate the effect of individual P2Y12 inhibitors at different DAPT durations longer than 6 months.Ethics and disseminationThis review will provide a comprehensive overview of the available evidence of the benefits and harms associated with extending DAPT beyond 12 months following PCI with stenting and the effects on clinically important subgroups. The results of this review will inform clinical and policy decisions regarding the optimal treatment duration of DAPT following PCI with stenting.Systematic review registrationPROSPERO no. CRD42018082587

Association of Testosterone Treatment With Alleviation of Depressive Symptoms in Men

“…The between-study heterogeneity was of considerable size only when 1 outlying study was included, suggesting the presence of either bias or moderating design factors. In agreement with Elliot et al, we conclude that, based on the Cochrane Risk of Bias assessment of the 27 RCTs, most testosterone treatment studies were at high or unclear risk of bias (see Turner et al, who suggest a publication bias in reporting of antidepressant trials that may lead to a 32% inflation of effect size for antidepressant treatments).…”

“…To our knowledge, the present meta-analysis is the largest examination to date of the association of testosterone treatment with depressive symptoms in men, including 27 RCTs comprising 1890 men. Replicating and extending previous work, we show evidence for a moderate antidepressant association of testosterone treatment compared with placebo, identifying an effect size of the overall analysis of Hedges g of 0.21. Based on reference ranges for depressive symptoms, this effect is translatable into a clinically relevant symptom reduction by 2.2 points on the BDI-II.…”

“…Two of us (A.W. and J.B.) further cross-validated candidate studies based on previous meta-analyses and systematic reviews to check whether there existed candidate studies that had not been identified by the systematic search …”

“…Although testosterone treatment emerged as a potent therapy for various disorders in hypogonadal men, defined as men with total testosterone levels of 345.82 ng/dL or less (to convert to nanomoles per liter, multiply by 0.0347), randomized placebo-controlled clinical trials (RCTs) of testosterone treatment in hypogonadal men that examine depressive symptoms have yielded inconsistent results . Results of RCTs investigating testosterone administration to men with MDD do not support this intervention as an effective antidepressant treatment .…”

“…Previous meta-analyses of RCTs have identified beneficial associations between testosterone treatment and reduced depressive symptoms in men, with subgroup analyses suggesting that testosterone treatment is most effective in middle-aged, hypogonadal, or HIV-positive men and men with mild depressive illness . A recently conducted meta-analysis examining testosterone treatment’s association with depression, quality of life, libido, and erectile function in hypogonadal men also identified a beneficial association for testosterone treatment for all 4 domains . Still, testosterone treatment is not recommended as an antidepressant treatment by clinical practice guidelines for depression treatment (National Institute for Health and Care Excellence) or by Endocrine Society clinical practice guidelines for testosterone therapy owing to prevailing uncertainty about its efficacy, age criteria, dosage, ideal duration, and method of application …”