Clinical impacts of additive use of olmesartan in hypertensive patients with chronic heart failure: the supplemental benefit of an angiotensin receptor blocker in hypertensive patients with stable heart failure using olmesartan (SUPPORT) trial

Yasuhiko Sakata, Nobuyuki Shiba, Jun Takahashi, Satoshi Miyata, Kotaro Nochioka, Masanobu Miura, Tsuyoshi Takada, Chiharu Saga, Tsuyoshi Shinozaki, Masafumi Sugi, Makoto Nakagawa, Nobuyo Sekiguchi, Tatsuya Komaru, Atsushi Kato, Mitsumasa Fukuchi, Eiji Nozaki, Tetsuya Hiramoto, Kanichi Inoue, Toshikazu Goto, Masatoshi Ohe, Kenji Tamaki, Setsuro Ibayashi, Nobumasa Ishide, Yukio Maruyama, Ichiro Tsuji, Hiroaki Shimokawa, SUPPORT Trial Investigators, SUPPORT Trial Investigators, M Fukuchi, T Goto, T Hiramoto, K Inoue, A Kato, T Komaru, M Ohe, N Sekiguchi, N Shiba, T Shinozaki, M Sugi, K Tamaki, T Hiramoto, K Inoue, A Kato, M Ogata, S Sato, M Sugi, N Ishide, S Ibayashi, Y Maruyama, I Ohno, K Tamaki, H Ogawa, M Kitakaze, I Tsuji, T Watanabe, K Sugiyama, S Oyama, E Nozaki, A Nakamura, T Takahashi, H Endo, S Fukui, S Nakajima, M Nakagawa, T Nozaki, T Yagi, S Horiguchi, E Fushimi, Y Sugai, S Takeda, K Fukahori, K Aizawa, M Ohe, T Tashima, K Sakurai, T Kobayashi, T Goto, M Matsui, Y Tamada, T Yahagi, A Fukui, K Takahashi, K Takahashi, Y Kikuchi, K Akai, H Kanno, J Kaneko, S Suzuki, K Takahashi, K Akai, D Katayose, S Onodera, T Hiramoto, S Komatsu, M Chida, K Iwabuchi, M Takeuchi, H Yahagi, N Takahashi, K Otsuka, Y Koseki, M Morita, T Shinozaki, T Ishizuka, N Onoue, N Yamaguchi, H Fujita, A Katoh, S Namiuchi, T Sugie, K Saji, T Takii, A Sugimura, J Ohashi, M Fukuchi, M Ogata, T Tanikawa, O Kitamukai, Y Matsumoto, K Inoue, J Koyama, T Tomioka, H Shioiri, Y Ito, H Kato, C Takahashi, A Kawana, Y Sakata, K Ito, M Nakayama, K Fukuda, J Takahashi, S Miyata, K Sugimura, K Sato, Y Matsumoto, M Nakano, T Shiroto, R Tsuburaya, K Nochioka, H Yamamoto, T Aoki, K Hao, M Miura, M Kondo, S Tatebe, S Yamamoto, H Suzuki, K Nishimiya, N Yaoita, M Sugi, Y Yamamoto, S Toda, Y Minatoya, Y Takagi, Y Hasebe, T Nihei, K Hanawa, K Fukuda, Y Sakata, J Takahashi, S Miyata, K Nochioka, M Miura, S Tadaki, R Ushigome, T Yamauchi, K Sato, K Tsuji, T Onose, R Abe, C Saga, J Suenaga, Y Yamada, J Kimura, H Ogino, I Oikawa, S Watanabe, M Saga, M Washio, K Nagasawa, S Nagasawa, S Kotaka, W Komatsu, R Hashimoto, Y Ikeno, T Suzuki, H Hamada, Yasuhiko Sakata, Nobuyuki Shiba, Jun Takahashi, Satoshi Miyata, Kotaro Nochioka, Masanobu Miura, Tsuyoshi Takada, Chiharu Saga, Tsuyoshi Shinozaki, Masafumi Sugi, Makoto Nakagawa, Nobuyo Sekiguchi, Tatsuya Komaru, Atsushi Kato, Mitsumasa Fukuchi, Eiji Nozaki, Tetsuya Hiramoto, Kanichi Inoue, Toshikazu Goto, Masatoshi Ohe, Kenji Tamaki, Setsuro Ibayashi, Nobumasa Ishide, Yukio Maruyama, Ichiro Tsuji, Hiroaki Shimokawa, SUPPORT Trial Investigators, SUPPORT Trial Investigators, M Fukuchi, T Goto, T Hiramoto, K Inoue, A Kato, T Komaru, M Ohe, N Sekiguchi, N Shiba, T Shinozaki, M Sugi, K Tamaki, T Hiramoto, K Inoue, A Kato, M Ogata, S Sato, M Sugi, N Ishide, S Ibayashi, Y Maruyama, I Ohno, K Tamaki, H Ogawa, M Kitakaze, I Tsuji, T Watanabe, K Sugiyama, S Oyama, E Nozaki, A Nakamura, T Takahashi, H Endo, S Fukui, S Nakajima, M Nakagawa, T Nozaki, T Yagi, S Horiguchi, E Fushimi, Y Sugai, S Takeda, K Fukahori, K Aizawa, M Ohe, T Tashima, K Sakurai, T Kobayashi, T Goto, M Matsui, Y Tamada, T Yahagi, A Fukui, K Takahashi, K Takahashi, Y Kikuchi, K Akai, H Kanno, J Kaneko, S Suzuki, K Takahashi, K Akai, D Katayose, S Onodera, T Hiramoto, S Komatsu, M Chida, K Iwabuchi, M Takeuchi, H Yahagi, N Takahashi, K Otsuka, Y Koseki, M Morita, T Shinozaki, T Ishizuka, N Onoue, N Yamaguchi, H Fujita, A Katoh, S Namiuchi, T Sugie, K Saji, T Takii, A Sugimura, J Ohashi, M Fukuchi, M Ogata, T Tanikawa, O Kitamukai, Y Matsumoto, K Inoue, J Koyama, T Tomioka, H Shioiri, Y Ito, H Kato, C Takahashi, A Kawana, Y Sakata, K Ito, M Nakayama, K Fukuda, J Takahashi, S Miyata, K Sugimura, K Sato, Y Matsumoto, M Nakano, T Shiroto, R Tsuburaya, K Nochioka, H Yamamoto, T Aoki, K Hao, M Miura, M Kondo, S Tatebe, S Yamamoto, H Suzuki, K Nishimiya, N Yaoita, M Sugi, Y Yamamoto, S Toda, Y Minatoya, Y Takagi, Y Hasebe, T Nihei, K Hanawa, K Fukuda, Y Sakata, J Takahashi, S Miyata, K Nochioka, M Miura, S Tadaki, R Ushigome, T Yamauchi, K Sato, K Tsuji, T Onose, R Abe, C Saga, J Suenaga, Y Yamada, J Kimura, H Ogino, I Oikawa, S Watanabe, M Saga, M Washio, K Nagasawa, S Nagasawa, S Kotaka, W Komatsu, R Hashimoto, Y Ikeno, T Suzuki, H Hamada

Abstract

We examined whether an additive treatment with an angiotensin receptor blocker, olmesartan, reduces the mortality and morbidity in hypertensive patients with chronic heart failure (CHF) treated with angiotensin-converting enzyme (ACE) inhibitors, β-blockers, or both. In this prospective, randomized, open-label, blinded endpoint study, a total of 1147 hypertensive patients with symptomatic CHF (mean age 66 years, 75% male) were randomized to the addition of olmesartan (n = 578) to baseline therapy vs. control (n = 569). The primary endpoint was a composite of all-cause death, non-fatal acute myocardial infarction, non-fatal stroke, and hospitalization for worsening heart failure. During a median follow-up of 4.4 years, the primary endpoint occurred in 192 patients (33.2%) in the olmesartan group and in 166 patients (29.2%) in the control group [hazard ratio (HR) 1.18; 95% confidence interval (CI), 0.96-1.46, P = 0.112], while renal dysfunction developed more frequently in the olmesartan group (16.8 vs. 10.7%, HR 1.64; 95% CI 1.19-2.26, P = 0.003). Subgroup analysis revealed that addition of olmesartan to combination of ACE inhibitors and β-blockers was associated with increased incidence of the primary endpoint (38.1 vs. 28.2%, HR 1.47; 95% CI 1.11-1.95, P = 0.006), all-cause death (19.4 vs. 13.5%, HR 1.50; 95% CI 1.01-2.23, P = 0.046), and renal dysfunction (21.1 vs. 12.5%, HR 1.85; 95% CI 1.24-2.76, P = 0.003). Additive use of olmesartan did not improve clinical outcomes but worsened renal function in hypertensive CHF patients treated with evidence-based medications. Particularly, the triple combination therapy with olmesartan, ACE inhibitors and β-blockers was associated with increased adverse cardiac events. This study is registered at clinicaltrials.gov-NCT00417222.

Keywords: Angiotensin II receptor blocker; Heart failure; Hypertension; Olmesartan.

© The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

Figures

Figure 1
Figure 1
Trial profile.
Figure 2
Figure 2
Time course in blood pressure. Blood pressure values are presented as mean ± standard deviations. There were no statistical differences in systolic or diastolic blood pressure at each point between the olmesartan and the control groups.
Figure 3
Figure 3
Kaplan–Meier curves for the primary endpoint for overall patients.
Figure 4
Figure 4
Kaplan–Meier curves for the primary endpoint for subgroups according to the baseline medication. (A) Patients treated with angiotensin-converting enzyme inhibitors but not with β-blockers. (B) Patients treated with β-blockers but not with angiotensin-converting enzyme inhibitors. (C) Patients treated with both angiotensin-converting enzyme inhibitors and β-blockers. ACEI, angiotensin-converting enzyme inhibitors; BB, β-blockers.

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