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Supplemental Digital Content is available in the text, Androgen deprivation therapy (ADT) is a cornerstone therapy for advanced prostate cancer (PCa). We hypothesized that cardiovascular (CV) risk is different across the various ADT modalities to compare their effects on CV morbidity and mortality, and all-cause mortality in patients with PCa. To investigate more in depth potential CV risk heterogeneity focusing on coronary (main outcome) and cerebrovascular risk, CV, and overall mortality. We performed a Medline and Embase query, without language restriction, since 1950 up to July 2014. We included randomized controlled trials (RCTs) and observational studies providing that they compared at least 1 ADT modality to another one or to placebo and they gave data on CV event or all-cause mortality. Sixty-eight studies out of 3419 met our eligibility criteria. Eleven observational studies were analyzed. Direct meta-analyses showed that antiandrogen was associated with a 30% decrease risk for myocardial infarction (MI) compared to GnRH agonists (RR, 0.70 [0.54–0.91]); combined androgen blockade (CAB) was associated with a 10% increase risk for stroke when compared to antiandrogen (RR, 1.10 [1.02–1.19]). With regard to RCTs, 57 were included: direct meta-analyses suggested that CAB was associated with a 10% decrease of all-cause mortality when compared to GnRH agonist (RR, 0.90 [0.82–1.00]). Network analysis could only be performed for all-cause mortality and it remains difficult to disentangle benefit (positive impact on cancer survival) and risk (including CV risk). The impact of the ADT modalities on CV morbidity remains difficult to quantify and more detailed prospective collection is required. Registration: PROSPERO, CRD42014010598.

Multiple novel oral anticoagulants (NOACs) and left atrial appendage closure (LAAC) devices have been tested against adjusted dose warfarin (VKA) in randomized controlled trials (RCTs) for stroke prophylaxis in non-valvular atrial fibrillation. No direct comparisons of the efficacy and safety

Hydrochlorothiazide (HCTZ) is widely used for hypertension, and prescriptions for HCTZ outnumber those for chlorthalidone (CTDN) by >20-fold in 2 recent surveys. Some have recently expressed a preference for CTDN. However, head-to-head trials testing the effect of the 2 drugs on cardiovascular events (CVEs) are lacking. We conducted a systematic review of randomized trials in which 1 arm was based on either HCTZ or CTDN followed by 2 types of network meta-analyses, a drug-adjusted analysis and an office systolic blood pressure–adjusted analysis. Nine trials were identified: 3 based on HCTZ and 6 based on CTDN. In the drug-adjusted analysis (n=50946), the percentage of risk reduction in congestive heart failure for CTDN versus HCTZ was 23 (95% CI, 2–39; P =0.032); and in all CVEs was 21 (95% CI, 12–28; P P =0.024). When the reduction in office systolic blood pressure was identical in the 2 arms, the risk for CVEs in HCTZ arms was 19% higher than in its nondiuretic comparator arms ( P =0.021). Relative to HCTZ, the number needed to treat with CTDN to prevent 1 CVE over 5 years was 27. In conclusion, CTDN is superior to HCTZ in preventing cardiovascular events. This cannot be attributed entirely to the lesser effect of HCTZ on office systolic blood pressure but may be attributed to the pleomorphic effects of alternative medications or to the short duration of action of HCTZ.

Meta-analyses that simultaneously compare multiple treatments (usually referred to as network meta-analyses or mixed treatment comparisons) are becoming increasingly common. An important component of a network meta-analysis is an assessment of the extent to which different sources of evidence are compatible, both substantively and statistically. A simple indirect comparison may be confounded if the studies involving one of the treatments of interest are fundamentally different from the studies involving the other treatment of interest. Here, we discuss methods for addressing inconsistency of evidence from comparative studies of different treatments. We define and review basic concepts of heterogeneity and inconsistency, and attempt to introduce a distinction between ‘loop inconsistency’ and ‘design inconsistency’. We then propose that the notion of design-by-treatment interaction provides a useful general framework for investigating inconsistency. In particular, using design-by-treatment interactions successfully addresses complications that arise from the presence of multi-arm trials in an evidence network. We show how the inconsistency model proposed by Lu and Ades is a restricted version of our full design-by-treatment interaction model and that there may be several distinct Lu–Ades models for any particular data set. We introduce novel graphical methods for depicting networks of evidence, clearly depicting multi-arm trials and illustrating where there is potential for inconsistency to arise. We apply various inconsistency models to data from trials of different comparisons among four smoking cessation interventions and show that models seeking to address loop inconsistency alone can run into problems. Copyright © 2012 John Wiley & Sons, Ltd.

e17608 Background: Despite consensus group recommendations for anti-emetic use in patients receiving highly emetogenic anthracycline and cyclophosphamide-based chemotherapy (A and C-CT), clinical e...

Osteoporosis is an under-recognized problem threatening men. Bisphosphonates are the main treatment but their comparative efficacy is unclear for men with osteoporosis. Therefore, we performed this systematic review with network meta-analyses to summarize the evidence of comparative efficacy of bisphosphonates in men with osteoporosis.We completed network meta-analyses with a frequentist model to compare the efficacy of different bisphosphonates. Randomized controlled trials investigating bisphosphonates used in men with osteoporosis were included. The primary outcome was the rate of patients with a new vertebral fracture. The secondary outcome was the rate of patients with a non-vertebral fracture, which was defined as any fractures reported other than vertebral fractures. Pairwise meta-analyses were performed to compare bisphosphonates with placebo. We included open-label studies in the analyses as a sensitivity analysis.Ten trials were included, using alendronate, ibandronate, risedronate, and zoledronic acid. No significant difference was found between any pairs of alendronate, ibandronate, risedronate, and zoledronic acid for both vertebral and non-vertebral fractures. Zoledronic acid ranked as the most effective in preventing vertebral fracture in primary osteoporosis. Risedronate ranked best in preventing non-vertebral fracture in both primary osteoporosis and corticosteroid-induced osteoporosis. In the sensitivity analyses with the open-label studies, the ranking order did not change.The current evidence for bisphosphonates used in men with osteoporosis is inadequate. On the basis of the current evidence, zoledronic acid is most effective at preventing vertebral fractures, while risedronate has the highest possibility to rank the first in preventing non-vertebral fracture in men with primary osteoporosis and corticosteroid-induced osteoporosis. More well-designed studies are needed to test our findings and to better know the comparative efficacy of bisphosphonate to prevent vertebral fracture in men with osteoporosis.

Background In network meta-analyses, several treatments can be compared by connecting evidence from clinical trials that have investigated two or more treatments. The resulting trial network allows estimating the relative effects of all pairs of treatments taking indirect evidence into account. For a valid analysis of the network, consistent information from different pathways is assumed. Consistency can be checked by contrasting effect estimates from direct comparisons with the evidence of the remaining network. Unfortunately, one deviating direct comparison may have side effects on the network estimates of others, thus producing hot spots of inconsistency.

Hydrochlorothiazide (HCTZ) is the thiazide widely prescribed to treat hypertension. (e.g., HCTZ represented 96p of all thiazide prescriptions in the Veterans Administration [Ernst 2010].) Some have recently expressed a preference for chlorthalidone (CTDN). However, no head-to-head randomized