Dose-Related Effects of Angiotensin Receptor Blockade on Renal Function in Heart Failure | Journal Scan

Study Questions:

What are the dose-related effects of losartan on renal function using data from the HEAAL (Heart failure Endpoint evaluation of Angiotensin II Antagonist Losartan) trial?


The HEAAL trial randomized patients with reduced ejection fraction to 150 mg or 50 mg losartan daily in 29 countries from 2001 to 2005. Patients included were New York Heart Association (NYHA) functional class II-IV, left ventricular ejection fraction 40%, on stable medical therapy for at least 2 weeks, and known intolerance to angiotensin-converting enzyme inhibitors (ACEIs). Serum electrolytes and serum creatinine were measured at months 1, 4, 9, and 12, and at every 6 months thereafter.


A total of 3,834 patients were followed for a median of 4.7 years. Compared with 50 mg, 150 mg losartan led to a greater reduction in estimated glomerular filtration rate (eGFR) at each time point. The mean difference was -3.79 ml/min/1.73 m2; p < 0.0001. This difference was driven by differences in early rate of changes. Although an increase in serum creatinine >0.3 mg/dl from baseline was associated with an increased risk of death or hospitalization for HF (hazard ratio [HR], 1.36; p < 0.0001), worsening renal function within 4 months of initiating therapy did not statistically increase the risk of death or hospitalization for heart failure (HR, 1.09; p = 0.20). Despite increased risk of worsening renal function, 150 mg losartan was associated with reduced risk of death or hospitalization for HF compared with 50 mg (HR, 0.85; p < 0.0001).


Although high-dose losartan is associated with increased risk of early eGFR decline, the beneficial effects remain a justification to maintain patients on this medication.


High-dose losartan still remains a drug of choice in patients with reduced ejection fraction who are intolerant to ACEIs, offering a mortality benefit as well as reduced hospitalizations for heart failure.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: Heart Failure, Angiotensin II, Angiotensin-Converting Enzyme Inhibitors, Creatinine, Electrolytes, Hospitalization, Losartan, Stroke Volume, Ventricular Function, Left

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