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Cox regressions were performed to assess the hazard ratios (HRs) of spironolactone medication for cardiovascular death and drug discontinuation in each group. The causal forest model revealed three representative covariates and participants were partitioned into four subgroups which were Group 1 (baseline BMI \u2264 31.71 kg\/m2 and baseline ALP \u2264 80 U\/L, n = 759); Group 2 (BMI \u2264 31.71 kg\/m2 and ALP &amp;gt; 80 U\/L, n = 1088); Group 3 (BMI &amp;gt; 31.71 kg\/m2, and WBC \u2264 6.6 cells\/\u03bcL, n = 633); Group 4 (BMI &amp;gt; 31.71 kg\/m2 and WBC &amp;gt; 6.6 cells\/\u03bcL, n = 832), respectively. In the four subgroups, spironolactone therapy reduced the risk of cardiovascular death in high-risk group (Group 4) with both high BMI and WBC count (HR: 0.76; 95% CI 0.58 to 0.99; P = 0.045) but increased the risk in low-risk group (Group 1) with both low BMI and ALP (HR: 1.45; 95% CI 1.02 to 2.07; P = 0.041; P for interaction = 0.020) but showed similar risk of drug discontinuation (P for interaction = 0.498).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study manifested the HTEs of spironolactone in patients with HFpEF. Spironolactone treatment in HFpEF patients is feasible and effective in patients with high BMI and WBC while harmful in patients with low BMI and ALP. Machine learning model could be meaningful for improved categorization of patients with HFpEF, ensuring a better individualized therapy in the clinical setting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.14068","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T01:44:54Z","timestamp":1665539094000},"page":"322-333","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Targeting Efficacy of Spironolactone in Patients with Heart Failure with Preserved Ejection Fraction: The TOPCAT Study"],"prefix":"10.1093","volume":"10","author":[{"given":"Hui-min","family":"Zhou","sequence":"first","affiliation":[{"name":"Cardiology Department, The First Affiliated Hospital of Sun Yat-Sen University , Guangzhou ,","place":["China"]},{"name":"NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University) , Guangzhou 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