Abstract
Background
Mortality is increased following a hospitalization for heart failure (HF). It is not clear whether outpatient intensification of diuretic confers the same increased risk in the general population with heart failure
Purpose
This study sought to assess 1-year mortality risk after worsening HF, defined either as hospitalization due to HF or as intensified diuretic therapy in an outpatient setting, in a complete nationwide cohort of patients with HF on angiotensin converting enzyme inhibitors/ angiotensin receptor blocker and beta blockers.
Methods
From nationwide administrative registers, we identified all patients in Denmark diagnosed with HF in 2001–2016 and prescribed angiotensin converting enzyme inhibitor/ angiotensin receptor blocker and beta blocker within 120 days. During follow-up we defined worsening HF by the following events: Inpatient worsening (HF readmission) and outpatient worsening (intensified diuretic therapy, defined as the first event of new addition or doubled dosage of loop diuretic therapy or new onset addition of thiazide to loop diuretic therapy). Patients with a worsening event were risk set matched to two HF controls each at time of the event – based on age, sex and calendar year. One-year mortality risk was estimated with Kaplan-Meier and multivariable Cox regression models.
Results
We included 74,990 patients, median age 71 years (interquartile range: 62–79), 36% women. During five years of follow up, 8,727 patients had an inpatient worsening event, and 12,290 had an outpatient worsening event as first event. Absolute risk of 1-year mortality was 22.6% (95%-confidence interval (95%-CI): 21.7%-23.5%) after inpatient worsening, 18.0% (95%-CI: 17.3%-18.7%) after outpatient worsening compared to 9.8% (95%-CI: 9.5%-10.1%) for the matched controls. In a multivariable Cox model adjusted ischemic heart disease, atrial fibrillation, chronic obstructive pulmonary disease and diabetes, the hazard ratio for mortality among patients experiencing inpatient worsening was 2.46 (95%-CI: 2.33–2.60) and for outpatient worsening was 1.87 (95%-CI: 1.77–1.97), compared with the matched HF controls as reference (figure 1). Among patients who had an outpatient worsening as first event, 1,245 (10.1%) had a subsequent HF readmission within one year.
Conclusion
In a nationwide cohort of patients with HF, outpatient worsening defined by a diuretic intensification was associated with almost 2-fold risk of mortality during the next year. Although HF hospitalization is associated with a higher risk, the need to intensify diuretics in the outpatient setting is a signal to review and intensify efforts to improve HF outcomes.
Acknowledgement/Funding
The Danish Heart Foundation, (grant number 17-R116-A7610-22048)
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