Optimal medical care and coronary flow capacity-guided myocardial revascularization vs usual care for chronic coronary artery disease: the CENTURY trial

Figures

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  Figure 1. Trial profile. The participants are the population presenting to the 651 physicians referring patients to the trial due to high-risk factors, suspected or known coronary artery disease, with or without symptoms

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  Figure 2. Positron emission tomography quantitative analysis. (A) Schematic of rest and stress mL/min/g, their ratio as coronary flow reserve and the combination of stress mL/min/g and coronary flow reserve as coronary flow capacity per regional pixel by positron emission tomography mapped for the left ventricle as percent of left ventricle in each severity range (see text and Supplementary data online, Figure S1 for additional details). Example of severely reduced coronary flow capacity map (blue) incurring high mortality risk for which coronary angiogram and potential revascularization may be appropriate depending on clinical circumstances, clinical judgement and informed patient consent. The automated processing for a pixel with severely reduced coronary flow capacity is shown having stress flow (perfusion) of 0.4 mL/min/g plus coronary flow reserve 0.7 (myocardial steal); 36% of left ventricle consists of pixels having stress mL/min/g ≤ 0.8 plus coronary flow reserve ≤1.2 colour-coded blue. For comparison, another pixel has normal stress perfusion of 2.3 mL/min/g plus coronary flow reserve of 3.1 and 22% of left ventricle having pixels with stress mL/min/g ≥ 2.17 and coronary flow…

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  Figure 3. Outcomes—risk factor change. The cumulative or summed risk score change (Δbaseline-5year summed risk score) for comprehensive care vs standard care groups. The (−) sign indicates a smaller or lower risk score vs a (+) risk score as being higher risk. At baseline, the summed risk score of comprehensive and standard groups are similar (see Supplementary data online, Figure S2). At 5-year follow-up, risk scores for the comprehensive care group move left towards lower risk, whereas scores for the standard care group move right towards higher risk (see Supplementary data online, Figure S2)

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  Figure 4. Kaplan–Meier survival plots for time to major adverse cardiac events or death. All 5-year analyses show significantly improved survival and reduced major adverse cardiac events in the comprehensive care group compared with the standard care group. Major adverse cardiac events. Kaplan–Meier and Cox regression modelling for death at up to over 11 years after randomization shows progressive divergence of survival probability favouring improved survival in the comprehensive over the standard care group. Cox regression modelling for time to major adverse cardiac events of death is in Supplementary data online, Figure S3. MACE, major adverse cardiac events

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  Figure 5. Cumulative all-cause mortality, death or non-fatal myocardial infarction, revascularization and major adverse cardiac events. Over extended follow-up these outcomes are significantly lower in the comprehensive care than in the standard care group (χ2 analysis) paralleling Kaplan–Meier and Cox regression modelling over extended follow-up in the prior figure

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  Figure 6. Frequency of medical contacts between participants and CENTURY staff by clinic visit, phone, email or letters related to lifestyle, medications or symptoms with 24/7 access. N = 57 877 for 1028 participants over 5 years. As per protocol, supportive clinic visits by the comprehensive group were significantly more frequent than for the standard group. The bar graph shows medians (upper and lower quartiles) with Wilcoxon P-values for the number of clinic visits and the number of medical contacts for standard vs comprehensive groups

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  Figure 7. Quantitative perfusion metrics—baseline to 5 years. The Kolmogorov–Smirnov test for coronary flow capacity cumulative histograms showed no differences between comprehensive and standard care groups at baseline, at five years or for baseline to 5-year changes. Similarly, there were no differences between comprehensive vs the standard care group for stress mL/min/g or coronary flow reserve at baseline or 5 years. As a normal reference, the coronary flow capacity Kolmogorov–Smirnov plots for two serial coronary flow capacity maps in the same person for 100 healthy young volunteers without risk factors (not in the trial) shows precise reproducibility that is significant less severe than for participants in this trial. KS, Kolmogorov–Smirnov

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  Figure 8. Revascularization. For participants undergoing revascularization at any time during the 5-years, coronary flow capacity before revascularization was more severe than without revascularization, significantly improved after revascularization but remained more severe after revascularization than participants without revascularization