Triple‐tg mice treated with 10 mg·kg−1 of TAK‐272 (imarikiren/SCO‐272), an orally active direct renin inhibitor, exhibited improvements in heart failure phenotypes, such as cardiac hypertrophy and survival rate; however, a dose of 300 mg·kg−1 was required to improve symptoms in CSQ‐tg mice. Here, REN is linked to cardiac hypertrophy.