PCI and CABG for Treating Stable Coronary Artery Disease: JACC Review Topic of the Week.

Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are considered revascularization procedures, but only CABG can prolong life in stable coronary artery disease. Thus, PCI and CABG mechanisms may differ. Viability and/or ischemia detection to guide revascularization have been unable to accurately predict treatment effects of CABG or PCI, questioning a revascularization mechanism for improving survival. By contrast, preventing myocardial infarction may save lives. However, the majority of infarcts are generated by non-flow-limiting stenoses, but PCI is solely focused on treating flow-limiting lesions. Thus, PCI cannot be expected to significantly limit new infarcts, but CABG may do so through providing flow distal to vessel occlusions. All comparisons of CABG to PCI or medical therapy that demonstrate survival effects with CABG also demonstrate infarct reduction. Thus, CABG may differ from PCI by providing "surgical collateralization," prolonging life by preventing myocardial infarctions. The evidence is reviewed here.

Statistical Primer: heterogeneity, random- or fixed-effects model analyses?

Heterogeneity in meta-analysis describes differences in treatment effects between trials that exceed those we may expect through chance alone. Accounting for heterogeneity drives different statistical methods for summarizing data and, if heterogeneity is anticipated, a random-effects model will be preferred to the fixed-effects model. Random-effects models assume that there may be different underlying true effects estimated in each trial which are distributed about an overall mean. The confidence intervals (CIs) around the mean include both within-study and between-study components of variance (uncertainty). Summary effects provide an estimation of the average treatment effect, and the CI depicts the uncertainty around this estimate. There are 5 statistics that are computed to identify and quantify heterogeneity. They have different meaning and give complementary information: Q statistic and its P-value simply test whether effect sizes depart from homogeneity, T2 and T quantify the amount of heterogeneity, and I2 expresses the proportion of dispersion due to heterogeneity. The point estimate and CIs for random-effects models describe the practical implications of the observed heterogeneity and may usefully be contrasted with the fixed-effects estimates.

The flaws in the detail of an observational study on transcatheter aortic valve implantation versus surgical aortic valve replacement in intermediate-risks patients.

The PARTNER group recently published a comparison between the latest generation SAPIEN 3 transcatheter aortic valve implantation (TAVI) system (Edwards Lifesciences, Irvine, CA, USA) and surgical aortic valve replacement (SAVR) in intermediate-risk patients, apparently demonstrating superiority of the TAVI and suggesting that TAVI might be the preferred treatment method in this risk class of patients. Nonetheless, assessment of the non-randomized methodology used in this comparison reveals challenges that should be addressed in order to elucidate the validity of the results. The study by Thourani and colleagues showed several major methodological concerns: suboptimal methods in propensity score analysis with evident misspecification of the propensity scores (PS; no adjustment for the most significantly different covariates: left ventricular ejection fraction, moderate-severe mitral regurgitation and associated procedures); use of PS quintiles rather than matching; inference on not-adjusted Kaplan-Meier curves, although the authors correctly claimed for the need of balancing score adjusting for confounding factors in order to have unbiased estimates of the treatment effect; evidence of poor fit; lack of data on valve-related death.These methodological flaws invalidate direct comparison between treatments and cannot support authors' conclusions that TAVI with SAPIEN 3 in intermediate-risk patients is superior to surgery and might be the preferred treatment alternative to surgery.

Incidence, Characteristics, Predictors, and Outcomes of Repeat Revascularization After Percutaneous Coronary Intervention and Coronary Artery Bypass Grafting: The SYNTAX Trial at 5 Years.

OBJECTIVES: The study sought to determine the incidence, predictors, characteristics, and outcomes of repeat revascularization during 5-year follow-up of the SYNTAX (Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery) trial. BACKGROUND: Limited in-depth long-term data on repeat revascularization are available from randomized trials comparing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). METHODS: Incidence and timing of repeat revascularization and its relation to the long-term composite safety endpoint of death, stroke, and myocardial infarction were analyzed in the SYNTAX trial (n = 1,800) using Kaplan-Meier analysis. RESULTS: At 5 years, repeat revascularization occurred more often after initial PCI than after initial CABG (25.9% vs. 13.7%, respectively; p < 0.001), and more often consisted of multiple repeat revascularizations (9.0% vs. 2.8%, respectively; p = 0.022). Significantly more repeat PCI procedures were performed on de novo lesions in patients after initial PCI than initial CABG (33.3% vs. 13.4%, respectively; p < 0.001). At 5-year follow-up, patients who underwent repeat revascularization versus patients not undergoing repeat revascularization had significantly higher rates of the composite safety endpoint of death, stroke, and myocardial infarction after initial PCI (33.8% vs. 16.6%, respectively; p < 0.001), and a trend was found after initial CABG (22.4% vs. 15.8%, respectively; p = 0.07). After multivariate adjustment, repeat revascularization was an independent predictor of the composite safety endpoint after both initial PCI (hazard ratio [HR]: 2.2; 95% confidence interval [CI]: 1.6 to 3.0; p < 0.001) and initial CABG (HR: 1.8; 95% CI: 1.2 to 2.9; p = 0.011). CONCLUSIONS: Repeat revascularization rates are significantly higher after initial PCI than after initial CABG for complex coronary disease. Repeat revascularization is an independent predictor of death, stroke, and myocardial infarction for myocardial revascularization.

Is transcatheter aortic valve implantation (TAVI) a cost-effective treatment in patients who are ineligible for surgical aortic valve replacement? A systematic review of economic evaluations.

OBJECTIVES: Health Technology Assessment (HTA) agencies often undertake a review of economic evaluations of an intervention during an appraisal in order to identify published estimates of cost-effectiveness, to elicit comparisons with the results of their own model, and to support local reimbursement decision-making. The aim of this research is to determine whether Transcatheter Aortic Valve Implantation (TAVI) compared to medical management (MM) is cost-effective in patients ineligible for surgical aortic valve replacement (SAVR), across different jurisdictions and country-specific evaluations. METHODS: A systematic review of the literature from 2007-2012 was performed in the MEDLINE, MEDLINE in-process, EMBASE, and UK NHS EED databases according to standard methods, supplemented by a search of published HTA models. All identified publications were reviewed independently by two health economists. The British Medical Journal (BMJ) 35-point checklist for economic evaluations was used to assess study reporting. To compare results, incremental cost effectiveness ratios (ICERs) were converted to 2012 dollars using purchasing power parity (PPP) techniques. RESULTS: Six studies were identified representing five reimbursement jurisdictions (England/Wales, Scotland, the US, Canada, and Belgium) and different modeling techniques. The identified economic evaluations represent different willingness-to-pay thresholds, discount rates, medical costs, and healthcare systems. In addition, the model structures, time horizons, and cycle lengths varied. When adjusting for differences in currencies, the ICERs ranged from $27K-$65K per QALY gained. CONCLUSIONS: Despite notable differences in modeling approach, under the thresholds defined by using either the local threshold value or that recommended by the World Health Organization (WHO) threshold value, each study showed that TAVI was likely to be a cost-effective intervention for patients ineligible for SAVR.

Acute pulmonary embolectomy.

Acute pulmonary embolism (PE) is a common condition frequently associated with a high mortality worldwide. It can be classified into non-massive, sub-massive and massive, based on the degree of haemodynamic compromise. Surgical pulmonary embolectomy, despite having been in existence for over 100 years, is generally regarded as an option of last resort, with expectedly high mortality rates. Recent advances in diagnosis and recognition of key qualitative predictors of mortality, such as right ventricular stress on echocardiography, have enabled the re-exploration of surgical pulmonary embolectomy for use in patients prior to the development of significant circulatory collapse, with promising results. We aim to review the literature and discuss the indications, perioperative workup and outcomes of surgical pulmonary embolectomy in the management of acute PE.