Targeting Efficacy of Spironolactone in Patients with Heart Failure with Preserved Ejection Fraction: The TOPCAT Study

Figures

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  Figure 1. An illustrative schematic for the causal tree model. We randomly selected half of the 3445 observations without replacement. Then, those selected patients were divided into two groups. One group was employed to construct a tree, and the other group was used to estimate treatment effects. Repeated this procedure 500 times and acquire 500 causal trees as a causal forest. Then, select the most representative tree from them.

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  Figure 2. Subgroups identified by the representative causal tree. Nodes indicate the percent of the sample in each subdivision of the data, with the covariate and split point identified underneath. For instance, Group 1 contains 23% of the data and includes participants with baseline BMI ≤ 31.71 and baseline ALP ≤ 80. Absolute risk reduction (ARR) refers to the primary outcome of the TOPCAT trial. BMI = body mass index. ALP, alkaline phosphatase; WBC, white blood cell; ARR, absolute risk reduction; TOPCAT, Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial.

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  Figure 3. Flow diagram for subject selection in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. BMI, body mass index; ALP, alkaline phosphatase; WBC, white blood cell.

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  Figure 4. Central illustration. Clinical subgroups in HFpEF categorized by causal forest model and efficacy and safety of spironolactone versus placebo among subgroups. Four subgroups were categorized according to the three representative covariates (BMI, ALP, and WBC count) screened out by the causal forest model. Four subgroups exhibited differential response to spironolactone medication. In the four subgroups, spironolactone therapy showed a great benefit in reducing the risk of cardiovascular death in the relatively high‐risk group (Group 4, HR for primary outcome: 0.76; 95% CI 0.58 to 0.99; P = 0.045) but increased the risk in the low‐risk group (Group 1, HR for primary outcome: 1.45; 95% CI 1.02 to 2.07; P = 0.041). The medication showed a similar risk of drug discontinuation compared with other groups. HR, hazard ratio.

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  Figure 5. Cumulative hazard curves for the primary composite endpoint. Cumulative hazard curves across treated and control groups are shown for participants.