Hypertrophic Cardiomyopathy Drug Treatment Disappoints

The most common cause of sudden cardiac death in young people is hypertrophic cardiomyopathy, an inherited condition that can lead to heart failure, angina, arrhythmia and sudden cardiac death. There is no medical treatment shown to halt or reverse the progression of the disease-just palliative care or surgery.

The most common cause of sudden cardiac death in young people is hypertrophic cardiomyopathy (HCM), an inherited condition that can lead to heart failure, angina, arrhythmia and sudden cardiac death.

So far, there is no medical treatment shown to halt of reverse the progression of the disease—just palliative care or surgery. But, based on pilot studies showing there may be benefits to taking angiotensin II receptor blockers, a research team in Copenhagen, Denmark, set out to see if losartan might be effective.

Reporting at the 2014 American Heart Association Scientific Sessions in Chicago, IL, Anna Axelsson, MD, of the Rigshospitalet, University of Copenhagen said the results of the trial, known as INHERIT, did not show a benefit.

The study was designed to include 132 patients to detect difference in left ventricular mass of 12g/m2 with a power of 90%, a 2-sided alpha of 5% and allowing for a drop-out rate of 10%. The inclusion criterion was overt HCM according to international criteria. Exclusion criteria included blood pressure >140/90 mmHg, LVEF <50% and significant valvular disease.

Patients were randomized to losartan (100 mg/d) or placebo for 12 months. LV mass was assessed by cardiac magnetic resonance imaging (CMR) in patients who had no ICD or pacemaker and by CT in patients with a device. Dense replacement fibrosis was defined as areas with delayed gadolinium enhancement on CMR.

A total of 133 patients were randomized. Demographic characteristics were: age 52±13 years (1 SD); 35% women; 44% had known, disease-causing sarcomere gene mutations; 12% had obstructive physiology (left ventricular outflow tract [LVOT] gradient =30 mmHg) and 83% had fibrosis at baseline CMR. Key baseline measures were: LV mass 211±74 g; MWT 23±6 mm; fibrosis 2% of LV mass (interquartile range 1-6%); LVOT gradient at rest 8 mmHg (5-14 mmHg) and LVOT gradient during Valsalva maneuver 14 mmHg (8-42 mmHg).

“There was no effect on left ventricular mass or exercise capacity,” Axelsson said. The drug, which “helps the heart relax” had few adverse effects and was safe,” she said.

Commenting on the study, Euan Ashley, MB, DPhil, MRCP, of Stanford University, said the study demonstrates, “A study in a rare disease is hard to do,” but at least allays concerns that the drug might have had harmful side effects. “There was strong evidence from a mouse study,” that the drug might work, he said, calling the effort study's attempt to track its effects in humans “an ambitious aim.”