Among older patients (≥75 years old), the incidence of the composite of hard endpoints was also lower in the olmesartan plus CCB group than in the olmesartan plus diuretic group (hazard ratio 0.64, 95% CI 0.42–0.97, P = 0.03), although the interaction was not significant (P = 0.12). In this subgroup, the incidence of stroke was also lower in the olmesartan plus CCB group (hazard ratio 0.63, 95% CI 0.38–1.02, P = 0.059) and the interaction between treatment and age subgroup was statistically significant (P = 0.019).
Over a median follow-up period of 3.3 years, there were no differences in the cardiovascular risk reduction conferred using olmesartan, an ARB, in combination with either a CCB or a diuretic. The incidence of SAEs, however, was significantly lower in the olmesartan plus CCB group than in the olmesartan plus diuretic group. Patients in the present study were well matched in terms of age, obesity, history of cardiovascular disease, cardiovascular risk factors, and antihypertensive medications. BP at baseline and 3 years were similar in both groups, with comparable reductions in BP in both groups.
Several studies have examined the effects of combinations of antihypertensive drugs with different mechanisms of action. For example, the ACCOMPLISH trial showed that the combination of an ACE inhibitor and a CCB was superior to that of an ACE inhibitor and a diuretic for preventing cardiovascular events , and the Combination Therapy of Hypertension to Prevent Cardiovascular Events trial showed that the combination of a CCB and a diuretic was superior to that of a CCB and a β-blocker . Among studies examining the efficacy of add-on antihypertensive drugs, the Losartan Intervention For Endpoint reduction in hypertension study showed that an ARB-based regimen with an add-on diuretic was superior to a β-blocker–based regimen with an add-on diuretic for preventing cardiovascular events , whereas the Anglo-Scandinavian Cardiac Outcomes Trial – Blood Pressure Lowering Arm showed that a CCB-based regimen with an add-on ACE inhibitor was superior to a β-blocker–based regimen with an add-on diuretic . The results of these two studies suggested that the combination of an ARB and a diuretic or a CCB and an ACE inhibitor had some advantages over that of a β-blocker and a diuretic for treating hypertension. In the present study, we compared two widely used combinations of hypertensive drugs: an ARB and a CCB, and an ARB and a diuretic.
The primary endpoint, a composite of cardiovascular morbidity and mortality, and its individual components were not significantly different between the two groups in our study, indicating that both combinations conferred similar reductions in cardiovascular risk in elderly hypertensive patients, consistent with earlier studies showing that BP lowering is essential to reduce cardiovascular morbidity and mortality in hypertensive patients [19–21]. Although the present results do not support the conclusion of the ACCOMPLISH trial  that the combination of a renin–angiotensin system (RAS) inhibitor and a CCB is superior to that of a RAS inhibitor and diuretic, we could not consider a smaller relative risk reduction such as 19.6% in the ACCOMPLISH trial, because the present study was specifically powered to detect a relative risk reduction of 33% between the two groups . Nevertheless, the reason why the present results do not support those of the ACCOMPLISH trial may be differences in the races of study patients and the use of an ACE inhibitor vs. an ARB. The higher salt sensitivity in the older Japanese patients (mean age: 73.6 years) in our study than that in the slightly younger predominantly white (83.5%) (mean age: 68.4 years) patients in the ACCOMPLISH trial may have caused greater efficacy of the combination of the RAS inhibitor and diuretic in our study relative to theirs. Another important issue is that stroke was the most common component of the primary endpoint (51.4%) in our study, whereas myocardial infarction (23.1%) and coronary revascularization (58.5%) were more common in the ACCOMPLISH trial. The different pattern of endpoints between the two trials may be related to differences in ethnicity and the severity of cardiac risk at enrolment. It is well known that the incidence of stroke is more strongly associated with BP than is myocardial infarction. Indeed, the two groups in our study achieved similar SBP with a similar incidence of stroke. Although the incidence of the primary endpoint was not significantly different between the two groups, the prespecified subgroup analyses showed that the incidence of stroke among patients aged at least 75 years tended to be lower in the olmesartan plus CCB group (P = 0.059), with a statistically significant interaction (P = 0.019), which should be confirmed in future studies.
There were more SAEs and also SAEs that required treatment discontinuation in the olmesartan plus diuretic group than in the olmesartan plus CCB group. Furthermore, hyperuricaemia was more common in the olmesartan plus diuretic group, even though low doses of diuretics were used. On the basis of these tolerability issues, we suggest that the combination of an ARB and CCB may be preferable to that of an ARB and diuretic for elderly hypertensive patients.
Some limitations warrant mention. First, we used the method of prospective, randomized, open-label blinded-endpoint trial, which may lead to some investigator bias. Because BP control was similar in both groups, however, it is unlikely that some investigator bias affected the main outcomes of this study. Regarding statistical power, the incidence of the primary endpoint was close to the expected incidence. Because the sample size was designed to detect a relative difference of 33%, however, more patients were necessary to detect the smaller than expected difference in the incidence of the primary endpoint. Another limitation is that we only enrolled Japanese elderly hypertensive patients, so the results may not be generalizable to other populations.
In conclusion, antihypertensive drugs are widely prescribed to reduce the risk of serious cardiovascular events in patients deemed to be at high risk of such events. The current clinical guidelines for the management of hypertension advocate the use of multiple antihypertensive drugs in combination to help reach BP targets. Although there is abundant evidence supporting the use of combination therapy, very few studies have compared different combinations of drugs. We found no marked differences in the cardiovascular risk reduction by using olmesartan together with either a CCB or a diuretic. When considering the safety aspects, however, a regimen consisting of olmesartan and a CCB may be preferable to olmesartan in combination with a diuretic. Well designed studies are needed to compare the cardiovascular risk reduction profiles and safety profiles of combination regimens based on an ARB, ACE inhibitor, or CCB.
We thank the collaborators and members of the COLM Study Group.
The present work was supported by a grant from Japan Heart Foundation. The Japan Heart Foundation had no input into the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.
T.O., T.S., H.R., I.S., K.Shimamoto., H.M., K.Shimada, S.I., M.H., T.I., S.T., J.H., S.K., G.K., N.U., K.H., M.O., N.T., T.I., S.U., N.K., and S.T. have received travel expenses, payment for speaking at meetings, or funding for research from one or more pharmaceutical companies that market antihypertensive drugs, including Daiichi Sankyo Co. Ltd. S.M. has no conflicts of interest to disclose.
Appendix COLM study committees
Executive and Writing Committee: T. Saruta (Co-Chair, Keio University), T. Ogihara (Co-Chair, Morinomiya University of Medical Sciences), H. Rakugi (Secretary, Osaka University Graduate School of Medicine), and I. Saito (Keio University).
Steering Committee: K. Shimamoto (Sapporo Medical University), S. Ito (Tohoku University Graduate School of Medicine), H. Matsuoka (Dokkyo Medical University), K. Shimada (Shin-Oyama City Hospital), M. Horiuchi (Ehime University Graduate School of Medicine), T. Imaizumi (Kurume University School of Medicine), and S. Takishita (University of the Ryukyus School of Medicine).
Protocol Committee: K. Shimada (Shin-Oyama City Hospital), N. Ura (Sapporo Nishimaruyama Hospital), K. Hayashi (Keio University), and H. Rakugi (Osaka University Graduate School of Medicine).
Endpoint Committee: J. Higaki (Ehime University Graduate School of Medicine), M. Odawara (Tokyo Medical University), N. Tanahashi (Saitama Medical University), and G. Kimura (Asahi Rousai Hospital).
Independent Data Monitoring Committee: S. Katayama (Saitama Medical University), S. Umemura (Yokohama City University Graduate School of Medicine), T. Ishimitsu (Dokkyo Medical University), N. Kashihara (Kawasaki Medical School), and S. Morita (Yokohama City University Graduate School of Medicine).
Statistical Committee: I. Saito (Keio University) and S. Teramukai (Kanazawa University Hospital).
Ethics committee: Y. Uetsuka (Tokyo Women's Medical University), M. Fujikawa (Edogawa City Office), R. Nagao (Marunouchi Minami Law Office), and M. Ito (Chibaken Certified Public Tax Accountants’ Association).
COLM study investigators
T. Anno, S. Aoyama, N. Arima, Y. Bando, Y. Dohi, H. Fujioka, M. Fukuda, S. Fukuda, M. Fukuta, Y. Futamura, Y. Hirakawa, K. Imaeda, H. Imai, A. Imamura, M. Ito, O. Ito, T. Ito, T. Iwa, J. Izumi, Y. Kaga, K. Kanematsu, Y. Kato, Y. Kawata, T. Kitamura, K. Kobayashi, M. Koyasu, S. Kuwabara, M. Kuzuya, M. Maekawa, H. Mihara, F. Mitsuguchi, T. Murohara, T. Narita, K. Negi, Y. Numaguchi, T. Ohya, N. Okayama, K. Okuma, N. Ozaki, N. Ozeki, K. Sato, T. Sawada, Y. Seino, M. Suezawa, T. Suzuki, Y. Suzuki, N. Takahashi, R. Takahashi, N. Tanaka, Y. Wakida, H. Watanuki, M. Watarai, K. Yamada, S. Yamashita, M. Yoshikane (Aichi), M. Goto, Y. Ishida, H. Kimura, K. Takahashi, N. Yashima (Akita), Y. Abe, S. Fujiwara, H. Higashino, M. Kaizuka, O. Minami, Y. Ogiu, T. Osanai, T. Sasaki, A. Sato, K. Sugimoto, H. Takahashi, K. Tanabe (Aomori), D. Azuma, C. Ibuki, H. Inoya, T. Iyo, M. Kusaka, M. Ogawa, Y. Okubo, H. Rinno, M. Sano, T. Shishikura, H. Takahara, M. Takano, T. Takemura, S. Yamamoto, Y. Yonemitsu (Chiba), M. Hasui, T. Honda, M. Igase, S. Kimoto, K. Kohno, S. Kondo, T. Oonishi, H. Saeki, T. Sunayama, H. Takahashi, C. Wakisaka, H. Watanabe, K. Watanabe (Ehime), Y. Iwahori (Fukui), Alan H.C. Lau, S. Ando, H. Eguchi, M. Fujino, J. Fukui, T. Gondo, S. Hatakeyama, K. Hirano, Y. Hirooka, H. Ikeda, T. Inou, T. Jinnouchi, T. Kadokami, H. Kai, H. Kameo, M. Kaneyuki, A. Katoh, H. Kishikawa, H. Koiwaya, K. Kusaba, S. Maeda, S. Maki, M. Matsumoto, T. Matsumoto, J. Matsumura, S. Matsuo, H. Meno, S. Miki, J. Miyagi, T. Miyauchi, S. Mori, M. Nagashima, S. Nagata, R. Nakamura, T. Nakamura, H. Niiyama, K. Noda, M. Nohara, Y. Ohta, I. Onitsuka, T. Otonari, S. Ouma, T. Sakisaka, K. Saku, K. Sasaki, S. Sasaki, Y. Sawayama, M. Shihara, K. Shiota, K. Shirakawa, Y. Tachikawa, S. Takemura, T. Takeuchi, M. Tanabe, M. Tanaka, H. Tashiro, M. Tatsukawa, T. Tsuchihashi, T. Tsuiki, T. Tsutsui, Y. Uehara, H. Umei, T. Yamada, J. Yamagata (Fukuoka), T. Ajihara, K. Hagiwara, S. Imamura, M. Inoue, I. Konno, K. Konta, Y. Kubota, H. Kumakawa, T. Kuwana, H. Mitsuhashi, Y. Miyazaki, J. Nagashima, M. Nambu, T. Nishimaki, M. Sato, Y. Taneda, T. Tezuka, T. Yabuki (Fukushima), F. Ando, Y. Fuwa, S. Umeda (Gifu), O. Araki, Y. Furushima, Y. Hattori, H. Hirabayashi, M. Horigome, J. Hoshino, C. Iguchi, H. Inamura, H. Kawauchi, S. Kogure, H. Kubo, F. Naganuma, T. Nagao, T. Nagao, T. Nagata, H. Nakashima, Y. Shimizu, H. Shoda, M. Tachibana, K. Yabe (Gunma), R. Kuwashima, R. Mouri, T. Murakami, H. Muraoka, S. Nomura, F. Okuno, N. Sasaki, R. Sasaki, T. Satoh, M. Shirataki, H. Sugino, H. Takahashi, H. Takemoto (Hiroshima), J. Ashihara, T. Betsuyaku, T. Fujita, T. Haga, M. Hayashi, Y. Hayashi, K. Hirasawa, Y. Ishii, R. Ishimoto, T. Komakine, M. Kyuma, I. Maeda, H. Matsuda, T. Matsuki, T. Matsumoto, T. Mito, M. Mizutani, H. Morimoto, S. Natori, T. Nishimiya, M. Nishimura, H. Oimatsu, H. Ooiwa, S. Saitoh, Y. Sasagawa, T. Segawa, H. Shuke, K. Sotozono, S. Takagi, S. Tanaka, M. Tashi, T. Tsubokura, Y. Ueno, K. Urabe, K. Yamauchi, H. Yoshida (Hokkaido), M. Amano, Y. Hiroumi, K. Iiyama, H. Kido, A. Kosaka, A. Nogami, M. Okada, M. Shigenobu, R. Shigeta, S. Takagi, T. Takamiya, T. Takemura, S. Tomimoto, T. Tsuboi (Hyogo), N. Abe, E. Akaogi, S. Iida, K. Ito, H. Jonouchi, T. Matsushima, H. Miura, M. Miyazaki, S. Okubo (Ibaraki), T. Araki, O. Iritani, K. Masuya, S. Morimoto, T. Nakahashi, Y. Wakasa, M. Yanagi (Ishikawa), Y. Abe, H. Ito, T. Kawakami, Y. Kawamorita, H. Okamoto, H. Omori, T. Suzuki, T. Yoshida (Iwate), K. Akiyama, S. Fujita, T. Hamamoto, K. Hasegawa, M. Hattori, H. Imachi, T. Ishida, H. Ishihama, K. Kaifu, H. Kishikawa, M. Kono, M. Kunishige, T. Maeta, H. Masugata, I. Matsumoto, N. Matsuoka, H. Miki, S. Mori, T. Morita, Y. Nishijima, E. Ohashi, Y. Okauchi, T. Okura, Y. Onishi, K. Ono, S. Senda, I. Seo, Y. Sugimoto, M. Tada, K. Yokoi, K. Yoshinare (Kagawa), K. Arikawa, Y. Hayashi, K. Iida, S. Miyata, H. Mizoguchi, A. Osako, S. Saishoji, I. Shimozono, S. Takenouchi, S. Tanaka (Kagoshima), T. Furuki, N. Hatori, T. Iwaki, E. Kametsu, T. Kawafune, I. Kobayashi, T. Kubo, I. Michishita, F. Nonaka, H. Numata, A. Ogata, K. Okubo, T. Sano, R. Sawada, T. Sekino, N. Shimizu, H. Shionoiri, H. Tsuchiya, Y. Watanabe, H. Yamamoto, G. Yasuda (Kanagawa), M. Aoki, Y. Iwasaki, H. Kawamoto, S. Kitagawa, M. Matsumoto, M. Nishinaga, M. Nishiyama, K. Tsuboi, I. Ueda, T. Yabe, H. Yamada, T. Yoshida (Kochi), K. Azuma, O. Doi, R. Fukami, Y. Horio, Y. Ichikawa, S. Ikeda, T. Inaba, S. Mimori, K. Ohmori, K. Sasaki, A. Sato, H. Toyama, Y. Toyama (Kumamoto), T. Hamasaki, H. Hayashi, T. Isono, S. Kageyama, K. Komaki, S. Matoba, H. Matsubara, T. Matubara, C. Nakagawa, D. Nishi, M. Nishi, K. Oiwa, H. Takamatsu, H. Takashima, T. Takegami, K. Takenaka, H. Yamada, Y. Yasuda (Kyoto), M. Horiguchi, J. Iemura, N. Isaka, T. Ishiga, T. Kato, T. Kitamura, M. Kobayashi, M. Setsuda, K. Shimono (Mie), M. Abe, T. Abe, Y. Abe, Y. Akino, H. Ebina, G. Hirasawa, K. Hirasawa, H. Kamada, M. Kishi, K. Kohama, S. Kyogoku, K. Matsuo, Y. Meguro, S. Miyasato, K. Morita, H. Nakagawa, Y. Otake, H. Saito, A. Sasaki, I. Sasaki, S. Sato, N. Uchida, Y. Utsumi, S. Yamaguchi (Miyagi), K. Hosokawa, Y. Ishiyama, S. Kariya, H. Komidori, M. Kuwabara, H. Ohta, S. Sonoda, M. Takii, N. Wake, N. Yokota (Miyazaki), A. Iijima, T. Shinozaki, T. Takeda (Nagano), A. Ito, H. Kawano, Y. Koide, H. Matsuoka, K. Nakao, K. Yamaguchi, A. Yamanaka (Nagasaki), Y. Furiya, T. Kimu, Y. Kuga, Y. Nishida, Y. Saito, K. Sugie, T. Takami, M. Yamasaki (Nara), Y. Kaneko, H. Kawabata, S. Nakayama (Niigata), Y. Abe, H. Ando, T. Fujino, K. Gotoh, T. Kakuma, I. Katsuragi, A. Kuroda, T. Masaki, K. Ninomiya, K. Okita, H. Ono, T. Watanabe, A. Yoshiiwa (Oita), K. Abe, S. Deguchi, F. Ikeda, H. Kataoka, N. Komai, K. Koten, K. Kusano, N. Maeda, H. Makino, S. Matano, T. Ohe, K. Shikata (Okayama), M. Gushiken, R. Hamada, K. Matsushima, T. Shimabukuro, S. Tohma (Okinawa), T. Akagi, F. Akai, T. Amatsu, N. Babaya, S. Ban, K. Fujii, M. Fujimoto, Y. Fujimura, S. Fukumoto, M. Funauchi, H. Hanada, K. Hasegawa, N. Hayashi, T. Hibuse, M. Higashida, H. Honde, A. Imagawa, Y. Imamura, S. Inoue, R. Ishii, K. Ishikawa, K. Ishitani, H. Ito, S. Kaito, A. Kamitani, K. Kamiya, N. Kasayuki, R. Kawanami, T. Kawasaki, Y. Kijima, K. Kinoshita, M. Kishibuchi, Y. Kitamura, M. Kobayashi, T. Kono, Y. Maeda, K. Masaki, H. Matsumoto, S. Matsuoka, R. Matsuwaka, K. Minamikata, M. Miyagawa, H. Miyamoto, M. Miyamoto, E. Miyazaki, K. Miyoshi, M. Mune, N. Nakagawa, Y. Nakagawa, F. Nakamura, T. Nakamura, K. Nakanishi, Y. Nakatani, J. Nariyama, H. Nishida, M. Nishino, M. Nishiyama, K. Nishizawa, R. Nohara, A. Nose, H. Ogasawara, R. Ogawa, Y. Ohno, M. Ojima, Y. Okuyama, H. Otani, S. Otani, H. Park, H. Saito, A. Sakai, H. Sakamoto, H. Sata, Y. Sekine, T. Shinozuka, T. Suga, K. Sugimoto, M. Sugiyama, K. Suyama, K. Suyama, J. Tachi, T. Takagi, C. Takaori, M. Takenaka, T. Tamai, K. Tanaka, Y. Tanaka, K. Tane, M. Taniura, N. Tatsuda, Y. Teramoto, K. Teranaka, S. Teranishi, J. Terasaki, K. Toki, K. Tsuji, Y. Tsuji, T. Tsunetoshi, K. Ujino, S. Umeki, N. Wakagi, N. Wakaki, K. Yamaguchi, Y. Yamamoto, S. Yanagitani, M. Yoshida, H. Yoshimoto, H. Yoshioka (Osaka), H. Ikeda, M. Matsumoto, K. Nagae, M. Nishiyama, K. Noda, M. Ohga (Saga), M. Akui, H. Aoki, J. Arafune, M. Arai, T. Arai, I. Asami, K. Eguchi, T. Fujino, H. Fujinuma, H. Fukata, J. Fukuda, T. Hamasaki, M. Haneda, I. Hisauchi, T. Hogi, M. Ichikawa, T. Iijima, H. Inoue, Y. Inoue, T. Kakinuma, H. Kanai, U. Kaneko, T. Kano, T. Katsumi, T. Kawashima, K. Kogure, O. Komuro, Y. Kubouchi, N. Kujirai, K. Kurokawa, T. Lee, K. Maeda, T. Majima, Y. Maruyama, S. Mashiba, K. Mashiko, K. Matsumoto, M. Matsuzawa, Y. Mitsugi, J. Morita, C. Nakajima, Y. Nakazato, Y. Nashida, H. Nasuhara, Y. Numajiri, T. Ogasawara, T. Okudaira, I. Osawa, N. Otani, A. Otsuka, Y. Ozawa, T. Sakai, Y. Sakai, K. Shimizu, T. Shinozaki, M. Shirai, K. Shiroma, H. Shuto, H. Suzuki, A. Tada, M. Takagi, K. Takahashi, N. Takahashi, A. Taniguchi, Y. Tonegawa, M. Toyoda, T. Tsuchiya, M. Uchida, H. Uchino, H. Wada, O. Wada, H. Yoshioka (Saitama), H. Horie, M. Ichikawa, K. Ikenoue, T. Kawashima, H. Mizuhara, S. Ono (Shiga), S. Ishikawa, K. Kawakami, S. Yano (Shimane), N. Kubota, A. Nakagawa, T. Shigemasa, S. Suwa (Shizuoka), T. Akabane, M. Amagai, Y. Asanobu, S. Horinaka, T. Iijima, K. Kasai, T. Kataoka, M. Kobayashi, T. Masuda, I. Nakano, M. Namekawa, A. Numabe, A. Ono, K. Sakata, I. Taguchi, T. Tomotsune, S. Toyoda (Tochigi), M. Arizumi, Y. Morimoto, A. Ota, S. Sawada, K. Yata (Tokushima), H. Akita, T. Akitsu, K. Amemiya, M. Ando, N. Aoki, J. Aoyagi, T. Baba, T. Degawa, S. Eto, K. Fujimoto, H. Fukuda, T. Furukawa, I. Goto, A. Hachiya, Y. Hanatani, K. Hara, T. Haruta, K. Hasegawa, T. Hatano, M. Hayashi, T. Hirano, M. Hiratsuka, Y. Horikawa, T. Horiuchi, M. Hosoya, K. Ichikawa, K. Iguchi, H. Imai, K. Ishibashi, K. Ishida, Y. Ishii, S. Ishiwata, T. Iwama, H. Kadota, S. Kaku, Y. Kamisaka, R. Kanbara, T. Kanematsu, A. Kashiwagi, I. Kawa, B. Kawai, M. Kawai, S. Kiuchi, T. Kiyozuka, S. Koba, H. Kobayashi, K. Koike, H. Kojima, E. Koshibu, Y. Koshibu, I. Kubo, K. Kuga, T. Kushiro, S. Miyakata, M. Miyakawa, F. Miyoshi, Y. Mochida, N. Moriyama, T. Myojo, M. Nagashima, H. Nakada, T. Nakai, T. Nakamura, Y. Nakaya, M. Nishizawa, S. Nishizawa, K. Oba, Y. Obu, N. Ohara, M. Okazaki, Y. Okazaki, K. Okumura, T. Ono, Y. Osamura, M. Otsuka, M. Ouchi, N. Sakamoto, Y. Sakata, S. Saneshige, M. Sasajima, T. Satoi, Y. Sengoku, K. Shibuya, H. Shimizu, K. Shimokado, M. Shoji, H. Tabata, A. Takahashi, H. Takakura, T. Takao, M. Taya, H. Tomonari, T. Tsunematsu, A. Uehata, T. Umezawa, H. Usui, T. Watanabe, Y. Yajima, F. Yamada, K. Yamada, A. Yamaguchi, T. Yamaguchi, K. Yamamoto, M. Yamamoto (Tokyo), T. Hamada, I. Hisatome (Tottori), K. Arita, M. Arita, E. Doi, H. Furuta, T. Hano, T. Hashizume, A. Hibino, N. Kodama, A. Saika, J. Ueda (Wakayama), T. Fujita, T. Ito, M. Sakano, T. Sugawara, H. Tachibana, H. Toda (Yamagata), S. Fujimoto, T. Furui, Y. Hadano, T. Kaneko, A. Kawabata, S. Kawamoto, M. Mezuki, M. Mochizuki, M. Nakatsuka, S. Ono, N. Tahara (Yamaguchi), M. Kuroda, and H. Manabe (Yamanashi).
Reviewer's Summary Evaluation
For decades the investigation of the treatment of arterial hypertension in randomized controlled trials has consisted of the theoretical comparison of two monotherapies to which later on and if required one, two, or more drugs were added in a nonrandomized way. In many of those studies different combination therapies were used during the trial coming to complicate the final conclusions of those trials. The present study compares two combinations using olmesartan as a common drug that combines either with a diuretic or with a calcium cannel blocker. This type of study design initiated with the ACCOMPLISH study is, in my opinion, the most adequate to test the capacity of what the great majority of patients with arterial hypertension require for the control of BP, combination therapy.
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