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Functional effects of losartan in hypertrophic cardiomyopathy-a randomised clinical trial
Anna Axelsson1, Kasper Iversen2, Niels Vejlstrup1
1Unit for Inherited Cardiac Diseases, Department of Cardiology, The Heart Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Insights
Losartan did not improve cardiac function or exercise capacity in hypertrophic cardiomyopathy (HCM) patients. The drug failed to modify disease progression, indicating angiotensin II receptor blockers are not suitable for overt HCM.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Hypertrophic cardiomyopathy (HCM) lacks disease-modifying treatments.
- Current therapies focus on symptom management rather than altering disease course.
Purpose of the Study:
- To evaluate the efficacy of losartan in improving cardiac function and exercise capacity in patients with HCM.
- To determine if losartan could ameliorate disease progression in overt hypertrophic cardiomyopathy.
Main Methods:
- A randomized, placebo-controlled study involving 133 patients with HCM.
- Patients received either losartan (100 mg/day) or placebo for 12 months.
- Cardiac function (echocardiography, LVEF, GLS, diastolic function, LA volume) and exercise capacity (METS) were assessed at baseline and follow-up.
Main Results:
- Losartan showed no significant difference compared to placebo in improving left ventricular ejection fraction (LVEF), global longitudinal strain, diastolic function, or left atrial volume.
- Exercise capacity (METS) did not differ between the losartan and placebo groups.
- Despite treatment, disease progression was observed in both groups, with a significant increase in left atrial volume and a decrease in LVEF.
Conclusions:
- Losartan treatment did not improve myocardial performance or alter disease progression in adult patients with overt HCM.
- These findings do not support the use of angiotensin II receptor blockers as disease-modifying agents in this patient population.
- Further research is needed to identify effective disease-modifying therapies for hypertrophic cardiomyopathy.
Objective:
There is a lack of disease-modifying treatments in hypertrophic cardiomyopathy (HCM). The aim of this randomised, placebo-controlled study was to assess if losartan could improve or ameliorate deterioration of cardiac function and exercise capacity.
Methods:
Echocardiography, exercise test and MRI or CT were performed at baseline and after 12 months in 133 patients (52±13 years, 35% female) randomly allocated to losartan (100 mg/day) or placebo.
Results:
Losartan had no effect on systolic function compared with placebo (mean difference for left ventricular ejection fraction (LVEF) 0% (95% CI -3% to 4%), p=0.84 or global longitudinal strain 0.7% (95% CI -0.2% to 1.6%), p=0.13). Neither Doppler measures of diastolic function, left atrial volume (mean difference 2 mL/m(2) (95% CI -4 to 8 mL/m(2)) p=0.53) nor exercise capacity (mean difference -0.3 metabolic equivalents (METS) (95% CI -1.0 to 0.3 METS), p=0.28) differed between the treatment groups. At follow-up, there was further progression of disease, with the most prominent impairment being an increase in left atrial volume of 6 mL/m(2) (95% CI 3 to 9 mL/m(2), p<0.0001) in both groups combined. LVEF decreased (mean change -2%, (95% CI -3% to -1%), p=0.037) and 4% of patients had end-stage HCM with a LVEF of less than 50% at the end of the study.
Conclusion:
Treatment with losartan had no effect on cardiac function or exercise capacity compared with placebo. Losartan fail to improve myocardial performance and failed to alter the progression of the disease. These findings do not support the use of angiotensin II receptor blockers as disease modifiers in adult patients with overt HCM.
Trial Registration Number:
NCT01447654-results.
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