High-sensitivity troponin assays for the early rule-out or diagnosis of acute myocardial infarction in people with acute chest pain: a systematic review and cost-effectiveness analysis.

BACKGROUND: Early diagnosis of acute myocardial infarction (AMI) can ensure quick and effective treatment but only 20% of adults with emergency admissions for chest pain have an AMI. High-sensitivity cardiac troponin (hs-cTn) assays may allow rapid rule-out of AMI and avoidance of unnecessary hospital admissions and anxiety. OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of hs-cTn assays for the early (within 4 hours of presentation) rule-out of AMI in adults with acute chest pain. METHODS: Sixteen databases, including MEDLINE and EMBASE, research registers and conference proceedings, were searched to October 2013. Study quality was assessed using QUADAS-2. The bivariate model was used to estimate summary sensitivity and specificity for meta-analyses involving four or more studies, otherwise random-effects logistic regression was used. The health-economic analysis considered the long-term costs and quality-adjusted life-years (QALYs) associated with different troponin (Tn) testing methods. The de novo model consisted of a decision tree and Markov model. A lifetime time horizon (60 years) was used. RESULTS: Eighteen studies were included in the clinical effectiveness review. The optimum strategy, based on the Roche assay, used a limit of blank (LoB) threshold in a presentation sample to rule out AMI [negative likelihood ratio (LR-) 0.10, 95% confidence interval (CI) 0.05 to 0.18]. Patients testing positive could then have a further test at 2 hours; a result above the 99th centile on either sample and a delta (Δ) of ≥ 20% has some potential for ruling in an AMI [positive likelihood ratio (LR+) 8.42, 95% CI 6.11 to 11.60], whereas a result below the 99th centile on both samples and a Δ of < 20% can be used to rule out an AMI (LR- 0.04, 95% CI 0.02 to 0.10). The optimum strategy, based on the Abbott assay, used a limit of detection (LoD) threshold in a presentation sample to rule out AMI (LR- 0.01, 95% CI 0.00 to 0.08). Patients testing positive could then have a further test at 3 hours; a result above the 99th centile on this sample has some potential for ruling in an AMI (LR+ 10.16, 95% CI 8.38 to 12.31), whereas a result below the 99th centile can be used to rule out an AMI (LR- 0.02, 95% CI 0.01 to 0.05). In the base-case analysis, standard Tn testing was both most effective and most costly. Strategies considered cost-effective depending upon incremental cost-effectiveness ratio thresholds were Abbott 99th centile (thresholds of < £6597), Beckman 99th centile (thresholds between £6597 and £30,042), Abbott optimal strategy (LoD threshold at presentation, followed by 99th centile threshold at 3 hours) (thresholds between £30,042 and £103,194) and the standard Tn test (thresholds over £103,194). The Roche 99th centile and the Roche optimal strategy [LoB threshold at presentation followed by 99th centile threshold and/or Δ20% (compared with presentation test) at 1-3 hours] were extendedly dominated in this analysis. CONCLUSIONS: There is some evidence to suggest that hs-CTn testing may provide an effective and cost-effective approach to early rule-out of AMI. Further research is needed to clarify optimal diagnostic thresholds and testing strategies. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013005939. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Drug-Eluting vs Bare-Metal Stents in Patients with Chronic Kidney Disease and Coronary Artery Disease: Insights from a Systematic Review and Meta-Analysis

BACKGROUND: Most drug-eluting stent (DES) trials have excluded patients with chronic kidney disease (CKD). The efficacy of DES implantation in patients with CKD is therefore not known. OBJECTIVES: To evaluate the outcomes with DES vs bare-metal stent (BMS) implantation in patients with CKD. METHODS AND RESULTS: MEDLINE, EMBASE, and CENTRAL were searched for studies including at least 100 patients with CKD (estimated glomerular filtration rate ≤60 mL/min/1.73 m2 or on dialysis) treated with DES or BMS and followed for at least 1 month and reporting outcomes of all-cause mortality, cardiovascular (CV) mortality, myocardial infarction (MI), target-vessel revascularization (TVR), and stent thrombosis (ST). Thirty-one studies (5 randomized) with 91,817 participants (49,081 DES and 42,736 BMS) fulfilled the inclusion criteria. DES was associated with lower all-cause mortality (relative risk [RR], 0.77; 95% confidence interval [CI], 0.71-0.84), CV mortality (RR, 0.51; 95% CI, 0.38-0.70), MI (RR, 0.90; 95% CI, 0.86-0.95), TVR (RR, 0.61; 95% CI, 0.47-0.80), and numerically lower ST (RR, 0.75; 95% CI, 0.55-1.01) when compared with BMS. Analysis by study type (RCTs vs non-RCTs) showed similar results for most outcomes (Pinteraction\u3e.05) except all-cause mortality, where there was no difference between DES vs BMS in RCTs (Pinteraction≤.04). The effects were greater with 2nd-generation DES vs BMS (for example, ST: RR, 0.38; 95% CI, 0.20-0.72). CONCLUSIONS: In patients with CKD, the available evidence, largely from observational studies, suggests significantly fewer events with DES vs BMS with even a lower ST rate with 2nd-generation DES. These findings should be tested in large, randomized trials