Functional effects of losartan in hypertrophic cardiomyopathy-a randomised clinical trial

Heart. 2016 Feb 15;102(4):285-91. doi: 10.1136/heartjnl-2015-308343. Epub 2015 Dec 9.

Abstract

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiotensin II Type 1 Receptor Blockers / adverse effects
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Cardiomyopathy, Hypertrophic / diagnostic imaging
  • Cardiomyopathy, Hypertrophic / drug therapy*
  • Cardiomyopathy, Hypertrophic / physiopathology
  • Denmark
  • Disease Progression
  • Echocardiography, Doppler
  • Exercise Test
  • Exercise Tolerance / drug effects*
  • Female
  • Humans
  • Losartan / adverse effects
  • Losartan / therapeutic use*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Recovery of Function
  • Stroke Volume / drug effects
  • Time Factors
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Ventricular Function, Left / drug effects*
  • Ventricular Remodeling / drug effects

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Losartan

Associated data

  • ClinicalTrials.gov/NCT01447654