Gyu Chul Oh1, Jung-Kyu Han1, Ki Hoon Han2, Min-Su Hyon3, Joon Hyung Doh4, Moo Hyun Kim5, Jin-Ok Jeong6, Jang-Ho Bae7, Sang Hyun Kim8, Byung-Su Yoo9, Sang Hong Baek10, Moo-Yong Rhee11, Sang-Hyun Ihm12, Jung Hoon Sung13, Young Jin Choi14, Soo-Joong Kim15, Kyung-Soon Hong16, Byoung Kwon Lee17, JangHyun Cho18, Eun Seok Shin19, Jay Young Rhew20, Hyunsu Kim21, Hyo-Soo Kim22. 1. Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. 2. Division of Cardiology, Department of Internal Medicine, Asan Medical Center, Seoul, Republic of Korea. 3. Division of Cardiology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea. 4. Division of Cardiology, Department of Internal Medicine, Inje University Ilsan-Paik Hospital, Goyang, Republic of Korea. 5. Division of Cardiology, Department of Internal Medicine, Dong-A University Hospital, Busan, Republic of Korea. 6. Division of Cardiology, Department of Internal Medicine, Chungnam National University Hospital, Daejon, Republic of Korea. 7. Division of Cardiology, Heart Center, Konyang University Hospital, Daejon, Republic of Korea. 8. Division of Cardiology, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea. 9. Division of Cardiology, Department of Internal Medicine, Wonju Christian Hospital, Wonju, Republic of Korea. 10. Division of Cardiology, Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul, Republic of Korea. 11. Division of Cardiology, Department of Internal Medicine, DongGuk University International Hospital, Goyang, Republic of Korea. 12. Division of Cardiology, Department of Internal Medicine, Bucheon St. Mary's Hospital, Bucheon, Republic of Korea. 13. Department of Cardiology, CHA Bundang Medical Center, Seongnam, Republic of Korea. 14. Department of Cardiology, Sejong General Hospital, Bucheon, Republic of Korea. 15. Division of Cardiology, Department of Internal Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea. 16. Division of Cardiology, Department of Internal Medicine, Chuncheon Sacred Heart Hospital, Chuncheon, Republic of Korea. 17. Division of Cardiology, Department of Internal Medicine, Gangnam Severance Hospital, Seoul, Republic of Korea. 18. Department of Cardiology, Heart Center, Saint Carollo Hospital, Sun-cheon, Republic of Korea. 19. Division of Cardiology, Department of Internal Medicine, Ulsan University Hospital, Ulsan, Republic of Korea. 20. Division of Cardiology, Department of Internal Medicine, Presbyterian Medical Center, Jeonju, Republic of Korea. 21. Division of Cardiology, Department of Internal Medicine, Kosin University Gospel Hospital, Busan, Republic of Korea. 22. Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address: hyosoo@snu.ac.kr.
Abstract
PURPOSE: Hypertension and dyslipidemia are 2 risk factors of cardiovascular disease that often present simultaneously. Traditionally, treatment of these multiple conditions required separate medications for each disease, which may result in poor compliance and thus lead to possible treatment failure. Fixed-dose combination (FDC) therapy with a single pill may be a solution in these situations. METHODS: This multicenter, 8-week, randomized, double-blind, Phase III study evaluated the efficacy and safety of FDC treatment with telmisartan (80 mg) and rosuvastatin calcium (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. Patients were randomly assigned to 4 groups: (1) FDC drug (80 mg of telmisartan and 20 mg of rosuvastatin); (2) 80 mg of telmisartan; (3) 20 mg of rosuvastatin; or (4) placebo. After 8 weeks of treatment, the change in mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP) between the FDC group and the rosuvastatin group, and the percent change in LDL-C between the FDC group and the telmisartan group, were compared. FINDINGS: A total of 210 patients were enrolled in the study (84 in the FDC group, 42 in the rosuvastatin group, 43 in the telmisartan group, and 41 in the placebo group). The reduction in blood pressure was significantly greater in the FDC group than in the rosuvastatin group after 8 weeks of treatment (least squares mean change from baseline, -16.1 [1.6] mm Hg vs -1.7 [2.2] mm Hg [P < 0.001] for MSSBP; -8.8 [1.0] mm Hg vs -1.6 [1.4] mm Hg [P < 0.001] for MSDBP). Least squares mean percent change in LDL-C from baseline was also significantly greater in the FDC group compared with the telmisartan group (-49.3% [2.2%] vs 1.5% [3.0%]; P < 0.001). FDC therapy also had a higher rate of achieving the treatment goal in both blood pressure (60% vs 45%; P = 0.024) and LDL-C (88.8% vs 16.3%; P < 0.001) compared with rosuvastatin or telmisartan alone, respectively. In regression analysis, higher baseline MSSBP, female sex, and lower body mass index were associated with increased reductions in MSSBP, whereas higher baseline LDL-C level and lower body mass index were associated with greater reductions in LDL-C. There were 48 adverse events in 36 patients (17.3% [36 of 208]), and 17 adverse drug reactions in 12 patients (5.8% [12 of 208]), indicating no significant differences in short-term safety among study groups. IMPLICATIONS: Treatment with an FDC drug containing telmisartan and rosuvastatin showed similar efficacy in lowering blood pressure and LDL-C levels compared with that of each single drug. ClinicalTrials.gov identifier: NCT01914432.
RCT Entities:
PURPOSE:Hypertension and dyslipidemia are 2 risk factors of cardiovascular disease that often present simultaneously. Traditionally, treatment of these multiple conditions required separate medications for each disease, which may result in poor compliance and thus lead to possible treatment failure. Fixed-dose combination (FDC) therapy with a single pill may be a solution in these situations. METHODS: This multicenter, 8-week, randomized, double-blind, Phase III study evaluated the efficacy and safety of FDC treatment with telmisartan (80 mg) and rosuvastatin calcium (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. Patients were randomly assigned to 4 groups: (1) FDC drug (80 mg of telmisartan and 20 mg of rosuvastatin); (2) 80 mg of telmisartan; (3) 20 mg of rosuvastatin; or (4) placebo. After 8 weeks of treatment, the change in mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP) between the FDC group and the rosuvastatin group, and the percent change in LDL-C between the FDC group and the telmisartan group, were compared. FINDINGS: A total of 210 patients were enrolled in the study (84 in the FDC group, 42 in the rosuvastatin group, 43 in the telmisartan group, and 41 in the placebo group). The reduction in blood pressure was significantly greater in the FDC group than in the rosuvastatin group after 8 weeks of treatment (least squares mean change from baseline, -16.1 [1.6] mm Hg vs -1.7 [2.2] mm Hg [P < 0.001] for MSSBP; -8.8 [1.0] mm Hg vs -1.6 [1.4] mm Hg [P < 0.001] for MSDBP). Least squares mean percent change in LDL-C from baseline was also significantly greater in the FDC group compared with the telmisartan group (-49.3% [2.2%] vs 1.5% [3.0%]; P < 0.001). FDC therapy also had a higher rate of achieving the treatment goal in both blood pressure (60% vs 45%; P = 0.024) and LDL-C (88.8% vs 16.3%; P < 0.001) compared with rosuvastatin or telmisartan alone, respectively. In regression analysis, higher baseline MSSBP, female sex, and lower body mass index were associated with increased reductions in MSSBP, whereas higher baseline LDL-C level and lower body mass index were associated with greater reductions in LDL-C. There were 48 adverse events in 36 patients (17.3% [36 of 208]), and 17 adverse drug reactions in 12 patients (5.8% [12 of 208]), indicating no significant differences in short-term safety among study groups. IMPLICATIONS: Treatment with an FDC drug containing telmisartan and rosuvastatin showed similar efficacy in lowering blood pressure and LDL-C levels compared with that of each single drug. ClinicalTrials.gov identifier: NCT01914432.