Role of Ischemic Heart Disease in Major Adverse Renal and Cardiac Events Among Individuals With Heart Failure With Preserved Ejection Fraction (from the TOPCAT Trial)

https://doi.org/10.1016/j.amjcard.2020.11.034Get rights and content

Despite improvements in the prognosis of patients with heart failure with reduced ejection fraction (HFrEF), established therapy for heart failure patients with preserved ejection fraction (HFpEF) is lacking. Additionally, ischemic heart disease adversely impacts the clinical course of HFrEF patients; however, its role in HFpEF is not fully understood. We conducted a post hoc analysis of propensity score matched patients from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial to compare HFpEF patients with versus without myocardial ischemia in terms of major adverse renal and/or cardiac events (MARCE). Of 3,445 participants, the prevalence of ischemia was 59%. For this analysis, we included 1,747 ischemic patients and 1,207 propensity matched nonischemic patients. Ischemia was associated with a 20% increased risk (HR = 1.20, 95% confidence interval [CI] = 1.042 to 1.382, p value = 0.0112) of major adverse renal and/or cardiac events (MARCE) in adjusted analyses. Other important predictors of MARCE were diabetes (hazard ratio [HR] = 1.60, 95% CI = 1.38 to 1.87, p <0.0001), dyslipidemia (HR = 1.30, 95% CI = 1.10 to 1.52, p = 0.001) and smoking (HR = 1.33, 95% CI = 1.04 to 1.69, p = 0.0197). Revascularization was not significantly associated with MARCE in the subgroup of ischemic HFpEF patients. Future work is warranted to develop tailored interventions for patients with both HFpEF and ischemic heart disease to mitigate the risk of MARCE .

Section snippets

Methods

The Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT) rationale and design have been previously described.10 In brief, TOPCAT was a multinational, double-blind, randomized, placebo-controlled trial that collectively enrolled 3,445 patients from 6 countries: United States, Canada, Russia, Republic of Georgia, Argentina, and Brazil. The primary objective of the trial was to evaluate the efficacy of spironolactone relative to placebo for the

Results

There were 3,445 participants in TOPCAT. A total of 2,023 (59%) had IHD at the time of enrollment. Before matching, ischemic patients were younger and had higher rates of diabetes, hypertension and dyslipidemia (Table 1). They were also predominantly male and had lower BMI than patients without IHD. After matching, there were 1,747 patients with IHD and 1,207 patients without IHD (Table 1). The average age of matched participants was 68.6 ± 9.6 years, with females (52%), and Caucasians (90%)

Discussion

In this post hoc analysis of TOPCAT data, we found that the prevalence of IHD in this trial of patients with HFpEF was 59%, and that the participants with IHD had a 20% higher risk of MARCE compared to those without. Factors including BMI, smoking, diabetes mellitus and dyslipidemia were also found to contribute to the risk of MARCE. To our knowledge, this is the first study to examine the relationship between myocardial ischemia and MARCE in HFpEF patients.

The observed IHD prevalence in HFpEF

Authors Contribution

Peter A. McCullough, MD, MPH: Conceptualization, Methodology, Design, Supervision, Interpretation, Critical revision, Final approval, Agreement to be accountable; Gelareh Rahimi, PhD: Data acquisition, Software, Formal analysis, Data Curation, Writing - Original Draft, Final approval, Agreement to be accountable; Kristen M. Tecson: Interpretation, Critical revision, Final approval, Agreement to be accountable; Osama Elsaid, MD: Interpretation, Critical revision, Final approval, Agreement to be

Disclosures

The authors declare that they have no known competing financial interests or personal relations that could have appeared to influence the work reported in this study.

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    This work was funded in part by the Baylor Health Care System Foundation.

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