An American trial investigated the potential of valsartan in slowing the course of disease in hypertrophic cardiomyopathy (HCM). The results showed a significantly positive influence on relative cardiac remodeling in the valsartan group.

Results of murine and pre-clinical human studies have pointed to TGF-β neutralization antibodies or sartans as possibility to prevent left ventricular (LV) hypertrophy and fibrosis in HCM. Thus, the phase 2 VANISH trial (NCT01912534) investigated whether disease evolution could be reduced by valsartan treatment in early sarcomeric HCM [1].

The presented primary analysis cohort included 178 patients who all initially received valsartan in an active run-in period with up-titration to a dose of 320 mg in adults or 160 mg/80 mg in children according to weight. Upon completion, the participants were randomized to further treatment with valsartan or placebo until the study ended after 2 years. All patients were aged between 8 and 45 years and had a (likely) sarcomeric variant with NYHA class 1/2, a maximal LV wall thickness (LVWT) of 12–25 mm and no signs of obstruction. Mean age of the cohort was around 23 years with 43% of participants under the age of 18 and 39% women. Baseline maximal LVWT ranged between 8.1 and 8.2 (z-score) or 16.4 and 17.9 mm in the placebo and valsartan group, respectively.

“In developing the primary endpoint, we carefully considered the challenges we would face in demonstrating a treatment response. Mainly, we recognised that the magnitude of impact of valsartan was unknown, our participants were healthy, and asymptomatic at enrolment and, therefore, clinical events would be extremely rare,” Prof. Carolyn Ho (Brigham and Women’s Hospital, MA, USA) stated. She further explained that they therefore strove to interrogate disease biology rather than traditional clinical outcomes by identifying moderate effects in 9 different cardiac metrics. These consisted of markers for myocardial injury and stress, morphology, and function. The effect size was then defined as change in composite z-score at 2 years compared to baseline.

The results showed a positive trial with between-group difference of 0.231 (P=0.001), which stood for a relative amelioration in cardiac remodeling. “In the individual components, improvement was most marked for NT-ProBNP level, LV end diastolic volume and e’ velocity, each individually significant after adjusting for covariates,” said Prof. Ho. Within the analysis of pre-specified subgroups, valsartan led to all in all consistent effects, with the most pronounced benefit in subjects with LVWT less than the median z-score of 7.3. However, treatment with valsartan did not result in significant amelioration of left atrial volume index or LV mass index.

Prof. Ho stressed that treatment with valsartan was safe with no excess of adverse events, no instances of hypotension, hyperkaliemia, or renal insufficiency. “The VANISH trial suggested that there is an opportunity to attenuate disease progression in sarcomeric HCM with a widely available and well-tolerated medication”, she concluded.

  1. Ho, C. VANISH trial results. Late-Breaking Science in Heart Failure, ESC Congress 2021, 27–30 August.