Valsartan stunts disease progression in early-stage sarcomer
In patients with early-stage sarcomeric hypertrophic cardiomyopathy, valsartan improved certain parameters of disease progression compared with placebo, researchers reported at the European Society of Cardiology Congress.

Studies in mouse models of HCM showed that activation of transforming growth factor (TGF)-beta played a major role in upregulation of profibrotic genetic pathways leading to clinically overt disease, and that losartan, an angiotensin receptor blocker which has some ability to inhibit TGF-beta activation, reduced the development of left ventricular hypertrophy and myocardial fibrosis; moreover, treatment was most beneficial when started early before onset of LV hypertrophy, Ho said.

For the VANISH trial, the researchers randomly assigned 178 asymptomatic patients with pathogenic variants in sarcomeric genes (mean age, 23.5 years; 39% female) to valsartan, an angiotensin receptor blocker, 320 mg per day or placebo for 2 years.

Researchers said a standard analysis plan was unlikely to be successful due to low likelihood of CV events in a short follow-up time, so the primary outcome was change in a composite z score between baseline and year 2; the z score included a composite of nine metrics of cardiac structure or function. An increase (positive change) in the composite z score indicates improvement, whereas a decrease indicates worsening.

For the composite z score, the adjusted mean change at 2 years was –0.095 in the placebo group vs. 0.136 in the valsartan group (between-group difference, 0.231; 95% CI, 0.098-0.364; P = .001), Ho said during the presentation.

The following components of the composite favored the valsartan group at 2 years:

- N-terminal pro-B-type natriuretic peptide (between-group difference, –0.25 pg/mL; 95% CI, –0.47 to –0.03; P = .025);

- LV end-diastolic volume index (between-group difference, 4.1 mL/m2; 95% CI, 0.06-8.14; P = .047); and

- E’ velocity (between-group difference, 0.35 cm/sec; 95% CI, 0.06-0.63; P = .017).

The results did not vary by sex, age or disease-causing gene, but the treatment effect of valsartan was greater in those who had baseline z score of LV wall thickness of 7.3 or below than in those who did not, she said.

She said the difference in treatment effect by LV wall thickness “supports the hypothesis that disease-modifying therapy may be most effective if given early in the disease to individuals with less cardiac remodeling.”

Serious adverse events were similar between the groups, and there were no cases of hypotension, hyperkalemia or renal insufficiency, Ho said.

“Disease progression stabilized or potentially improved” in the valsartan group, researchers said during the presentation. “The VANISH trial suggests there is an opportunity to attenuate disease progression in sarcomeric HCM with a widely available and well-tolerated medication.”