Influence of documented history of coronary artery disease on outcomes in patients admitted for worsening heart failure with reduced ejection fraction in the EVEREST trial

Abstract

AimsData on the prognosis of heart failure (HF) patients with coronary artery disease (CAD) have been conflicting. We describe the clinical characteristics and mode-specific outcomes of HF patients with reduced ejection fraction (EF) and documented CAD in a large randomized trial. Methods and resultsEVEREST was a prospective, randomized trial of vasopressin-2 receptor blockade, in addition to standard therapy, in 4133 patients hospitalized with worsening HF and reduced EF. Patients were classified as having CAD based on patient-reported myocardial infarction (MI) or coronary revascularization. We analysed the characteristics and outcomes [all-cause mortality and cardiovascular (CV) mortality/HF hospitalization] of patients with and without documented CAD. All events were centrally adjudicated. Documented CAD was present in 2353 patients (57%). Patients with CAD were older and had more co-morbidities compared with those without CAD. Patients with CAD were more likely to receive a beta-blocker, but less likely to receive an angiotensin-converting enzyme (ACE) inhibitor or aldosterone antagonist (P , 0.01). After risk adjustment, patients with documented CAD had similar mortality [hazard ratio (HR) 1.12, 95% confidence interval (CI) 0.97-1.30], but were at an increased risk for CV mortality/ HF hospitalization (HR 1.25, 95% CI 1.12-1.41) due to an increased risk for HF hospitalization (HR 1.26, 95% CI 1.10 -1.44). Patients with CAD had increased HF-and MI-related events, but similar rates of sudden cardiac death. ConclusionDocumented CAD in patients hospitalized for worsening HF with reduced EF was associated with a higher burden of co-morbidities, lower use of HF therapies (except beta-blockers), and increased HF hospitalization, while all-cause mortality was similar.--

Coronary artery disease and 10‐year outcome after hospital admission for heart failure with preserved and with reduced ejection fraction

“…In our cohort, documented CAD was present in 25% of patients with HFPEF and in 39% of patients with HFREF—figures that are very similar with those reported by Henkel et al In contrast, with our findings, the frequency of CAD was slightly higher among patients with HFPEF included in the Irbesartan in Heart Failure with Preserved Ejection Fraction Study (I‐Preserve) and reached 65% in the angiographic study reported by O'Connor et al Our study used a clinical definition of CAD that probably led to an underestimation of the true proportion of patients with coronary disease. However this definition is, in our opinion, the most straightforward and was validated by previous reports …”

“…The prevalence of CAD in different cohorts of HF patients is extremely variable depending on the characteristics of the populations and the criteria used for the definition of CAD . Randomized HF clinical trials report higher frequency of CAD compared with epidemiological studies . In our cohort, documented CAD was present in 25% of patients with HFPEF and in 39% of patients with HFREF—figures that are very similar with those reported by Henkel et al In contrast, with our findings, the frequency of CAD was slightly higher among patients with HFPEF included in the Irbesartan in Heart Failure with Preserved Ejection Fraction Study (I‐Preserve) and reached 65% in the angiographic study reported by O'Connor et al Our study used a clinical definition of CAD that probably led to an underestimation of the true proportion of patients with coronary disease.…”

“…Classical studies conducted in HFREF which included angiographic criteria for CAD have demonstrated a strong link between CAD and mortality . However, in recent analyses, documented CAD did not have an impact on mortality, but increased the risk of readmission for HF . These latter studies had relatively short follow‐up.…”

“…Coronary artery disease (CAD) is the major cause of heart failure (HF) in contemporary Western populations . Although CAD has traditionally been reported to adversely impact long‐term outcome in heart failure with reduced ejection fraction (HFREF), recent data are less convincing in this regard . The excess mortality associated with CAD in a post‐hoc analysis of the BEST (Beta‐blocker Evaluation of Survival Trial) trial could not be demonstrated in patients with systolic HF included in the EVEREST (Efficacy of Vasopressin Antagonist in Heart Failure Outcome Study with Tolvaptan) trial .…”

Reframing the association and significance of co‐morbidities in heart failure

“…CAD is responsible for >50% of incident cases of HF in North America and Europe, whereas MI is the primary clinical intermediate between CAD and HF . The presence of underlying CAD adversely affects outcomes of HF patients regardless of the underlying LVEF . Angiographic evidence of CAD is a marker of worse prognosis in HF, with the mortality risk being increased by 250% in some reports .…”