A systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluating the core components of cardiac rehabilitation (CR), nutritional counseling (NC), risk factor modification (RFM), psychosocial management (PM), patient education (PE), and exercise training (ET)) was undertaken. Published RCTs were identified from database inception dates to April 2017, and risk of bias assessed using Cochrane’s tool. Endpoints included mortality (all-cause and cardiovascular (CV)) and morbidity (fatal and non-fatal myocardial infarction (MI), coronary artery bypass surgery (CABG), percutaneous coronary intervention (PCI), and hospitalization (all-cause and CV)). Meta-regression models decomposed treatment effects into the main effects of core components, and two-way or all-way interactions between them. Ultimately, 148 RCTs (50,965 participants) were included. Main effects models were best fitting for mortality (e.g., for all-cause, specifically PM (hazard ratio HR = 0.68, 95% credible interval CrI = 0.54–0.85) and ET (HR = 0.75, 95% CrI = 0.60–0.92) components effective), MI (e.g., for all-cause, specifically PM (hazard ratio HR = 0.76, 95% credible interval CrI = 0.57–0.99), ET (HR = 0.75, 95% CrI = 0.56–0.99) and PE (HR = 0.68, 95% CrI = 0.47–0.99) components effective) and hospitalization (e.g., all-cause, PM (HR = 0.76, 95% CrI = 0.58–0.96) effective). For revascularization (including CABG and PCI individually), the full interaction model was best-fitting. Given that each component, individual or in combination, was associated with mortality and/or morbidity, recommendations for comprehensive CR are warranted.
Decision-analytic software commonly used to implement discrete Markov models requires transitions to occur between simulated health states either at the beginning or at the end of each cycle. The result is an over- or underestimation, respectively, of quality-adjusted life expectancy and cost, compared with the results that would be obtained if transitions were modeled to occur randomly throughout each cycle. The standard half-cycle correction (HCC) is used to remedy the bias. However, the standard approach to the HCC is problematic: It does not account for discounting or for the shape of intermediate state membership functions. Application of the standard approach to the HCC also has no numerical effect on the resulting incremental cost-effectiveness ratio or change in net health benefit under certain circumstances. Alternatives to the standard HCC, in order of ease of use, include no correction, the life-table approach, the cycle-tree method, and a correction based on Simpson's rule. For less complex decision models in which the computational burden is not large, reducing the cycle length to a month or less and using no correction should result in small estimation biases. With more complex models, where cycle lengths larger than 1 month may be necessary to make computation feasible, we recommend the cycle tree approach. The latter is relatively easy to apply and has an intuitive appeal: Hypothetical subjects who transition from one state to another, on average halfway through a cycle, should receive half of the value associated with the state from which they come and half the value of the state to which they are going.
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