The association between high-dose diuretics and clinical stability in ambulatory chronic heart failure patients

Objective: In chronic heart failure (HF), diuretic doses increase as the disease progresses, often after hospitalization for instability, and have been associated with worsening renal function and increased mortality. Methods and Results: A prospective observational analysis of 183 patients in an advanced HF clinic stratified at baseline by diuretic dose (low dose <= 80 mg, high dose > 80 mg furosemide equivalent) was performed. All patients were followed for 1 year, and the primary outcome was a combined HF event of admission for HF, cardiac transplant, mechanical cardiac support, or death. Compared with patients taking low-dose diuretics (n = 113), patients taking high-dose diuretics (n = 70) had more markers of increased cardiovascular risk and were more likely to have a history of recent instability (33% vs 4.4% in low dose, P < .001). High doses of diuretics were a strong univariate predictor of subsequent HF events (hazard ratio 3.83, 95% confidence interval 1.82-8.54); however, after adjustment for clinical stability, diuretic dose no longer remained significant (hazard ratio 1.53, 95% confidence interval 0.58-4.03). Conclusion: High-dose diuretics may be more of a marker than a cause of instability. A history of HF stability during the past 6 months is associated with an 80% lower risk of an HF event during the next year, independently of baseline diuretic dose.