STICH (Surgical Treatment for Ischemic Heart Failure) trial enrollment

Abstract

Objectives: The aim of this study was to assess the influence of enrolling site location and enrollment performance on the generalizability of STICH (Surgical Treatment for Ischemic Heart Failure) trial results.

Background: The international STICH trial seeks to define the role of cardiac surgery for patients with ischemic cardiomyopathy.

Methods: Baseline characteristics of 2,136 randomized STICH patients were entered into a multivariate equation created using the Duke Databank for Cardiovascular Diseases to predict their 5-year risk for death without cardiac surgery. Patients ordered by increasing predicted risk were assigned to 1 of 32 risk at randomization (RAR) groups created to share one-thirty-second of total predicted deaths. Numbers of patients sharing the same RAR group were compared between higher and lower enrolling site groupings and for countries tending to enroll high- or low-risk patients.

Results: Country of enrollment was a stronger determinant of risk diversity than site enrollment performance among patients enrolled at 127 sites in 26 countries. Mean RAR differences among countries ranged from 9.4 (Singapore) to 18.6 (Germany). However, 1,614 of 2,136 patients (76%) from countries enrolling lower-risk patients shared the same RAR group with patients from countries enrolling higher-risk patients. Baseline characteristics responsible for risk differences of patients enrolled in the 2 country groupings were sufficiently similar to exert little influence on clinical decision making.

Conclusions: STICH randomized patients are characterized by a continuous spectrum of risk, without discordant dominance from any site or country. Clinical site diversity promises to enhance the generalization of STICH trial results to a broad population of patients with ischemic cardiomyopathy. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease; NCT00023595).

Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1. Risk at Randomization Development

The continuous green line represents the 2136 data points of individual patient mortality predicted from the multivariable model. The interrupted green lines represent total predicted deaths for all patients in each RAR group. The interrupted blue lines depict the total number of patients in each RAR group. The interrupted orange line represents the RAR group mortality assigned to each patient in each RAR group.

Figure 2. Schema of Patient Enrollment

This schematic depiction of the STICH trial design includes numbers of patients randomized to each stratum. Treatment assignments were MED only for 602 patients, CABG added to MED for 1033 patients, and CABG and SVR added to MED for 501 patients. The 76 Stratum B patients assigned to MED + CABG treatment are used to address both the surgical revascularization hypothesis and the SVR hypothesis. Therefore, 2136 randomized patients provided 2212 patients with potential for primary endpoints for analysis of either or both hypotheses.

Figure 3. Patients and Corresponding Clinical Characteristics by RAR

This histogram depicts the individual patients at each RAR interval. The corresponding median age, ejection fraction, and Duke CAD index for each RAR group and the percent of patients in each RAR group with baseline creatinine ≥1.5, ≥ NYHF class III, diabetes, mitral regurgitation ≥3+, and vascular disease provided a comprehensive summary of the components of risk for the entire population.

Figure 4. Country Enrollment by Enrolled Cohort Mean RAR

Countries ranked by the patient-weighted RAR mean show a two-fold range of difference from the lowest 9.4 (Singapore) to highest 18.6 (Germany) patient-weighted RAR mean. The numbers of patients enrolled in each country and cumulative patient enrollment by increasing RAR show the diversity of enrollment performance by country throughout the spectrum of patient risk of enrolling countries. The patient-weighted mean RAR index was calculated by multiplying the numbers of patients enrolled by each country by the index number of each RAR interval. The sum of these products is divided by the total numbers of patients enrolled by that country to produce the patient-weighted mean RAR.

Figure 5. RAR Profile by Country Mean Patient Risk

A total of 1,614 (76%) of 2,136 patients shared the same RAR grouping despite intentional creation of two cohorts to maximize imbalance among countries based on the average baseline risk of patients randomized. RAR groups 1-12 included more patients from countries with low patient-weighted mean RAR, and RAR groups 22-32 included more patients from countries with high patient-weighted mean RAR. RAR groups 10-21 reflected the most even distribution of patients from the two country groupings of sites. The baseline characteristics of patients in these two groupings are compared in Table 1.