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Efficacy of azilsartan on left ventricular diastolic dysfunction compared with candesartan: J-TASTE randomized
Shin Ito1,2, Hiroyuki Takahama1,3, Masanori Asakura2,4
1Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.
Insights
Azilsartan did not significantly improve left ventricular diastolic function compared to candesartan in hypertensive patients with heart failure. Further research is needed to confirm azilsartan
Area of Science:
- Cardiology
- Pharmacology
Background:
- Heart failure with preserved ejection fraction (HFpEF) is linked to high morbidity and mortality due to ventricular and vascular stiffness.
- Azilsartan, an angiotensin receptor blocker, has high myocardial and vascular affinities, suggesting potential benefits for diastolic function.
Purpose of the Study:
- To compare the efficacy of azilsartan versus candesartan in improving left ventricular (LV) diastolic function in hypertensive patients with HFpEF or HF with mildly reduced ejection fraction (HFmrEF).
Main Methods:
- A randomized, open-label trial involving 193 hypertensive patients with HF and LV ejection fraction ≥45%.
- Patients were assigned to receive either azilsartan (20 mg) or candesartan (8 mg) daily for 48 weeks.
- The primary endpoint was the change in the ratio of early diastolic transmitral flow velocity (E) to early diastolic mitral annular velocity (e') (E/e').
Main Results:
- The adjusted least-squares mean change in E/e' was -0.8 for azilsartan and 0.2 for candesartan, with a non-significant difference of -1.0 (P=0.057).
- Median change in left atrial volume index was -2.7 mL/m² for azilsartan versus 1.4 mL/m² for candesartan (P=0.091).
- Adverse events related to hypotension and hyperkalemia were similar between groups.
Conclusions:
- This study did not provide strong evidence that azilsartan improves LV diastolic dysfunction in the target patient population.
- Further confirmatory studies are required to establish the role of azilsartan in managing HFpEF and HFmrEF.
Abstract:
Characterized by ventricular and vascular stiffness, heart failure with preserved ejection fraction (HFpEF) has led to high morbidity and mortality. As azilsartan is an angiotensin receptor blocker with the highest myocardial and vascular affinities, azilsartan may improve the left ventricular (LV) diastolic function in patients with hypertension and either HFpEF or HF with mildly reduced ejection fraction (HFmrEF) more than candesartan. In this randomized, open-label trial, we randomly assigned 193 hypertensive patients with HF and LV ejection fraction ≥ 45% to 20 mg of azilsartan (n = 95) or 8 mg of candesartan (n = 98), once daily for 48 weeks. After the initiation of treatment, changes in the doses of the study drugs were permitted based on the patient's conditions, including blood pressure (median dose at 48 weeks: azilsartan 20.0 mg/day, candesartan 8.0 mg/day). The primary endpoint was the baseline-adjusted change in the ratio of peak early diastolic transmitral flow velocity (E) to early diastolic mitral annular velocity (e') (E/e'). Adjusted least-squares mean (LSM) change in E/e' was - 0.8 (95% confidence interval [CI] - 1.49 to - 0.04) in the azilsartan group and 0.2 (95% CI - 0.49 to 0.94) in the candesartan group, providing the LSM differences of - 1.0 (95% CI - 2.01 to 0.03, P = 0.057). The median change in left atrial volume index was - 2.7 mL/m2 with azilsartan vs 1.4 mL/m2 with candesartan (P = 0.091). The frequency of adverse events related to hypotension and hyperkalemia did not differ between the groups. The current study did not provide strong evidence that azilsartan improves LV diastolic dysfunction, and further confirmatory study is required.
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