Hae-Young Lee1, Seok-Yeon Kim2, Kee-Joon Choi3, Byung-Su Yoo4, Dong-Hun Cha5, Hae Ok Jung6, Dong-Ryeol Ryu7, Joon Hyouk Choi8, Kwang Je Lee9, Tae Ho Park10, Ju Hyeon Oh11, Sang Min Kim12, Ji-Yong Choi13, Kye Hun Kim14, Jaemin Shim15, Woo-Shik Kim16, Si-Wan Choi17, Dae-Gyun Park18, Pil-Sang Song19, Taek-Jong Hong20, Moo-Yong Rhee21, Seung-Woon Rha22, Seung Woo Park23. 1. Seoul National University Hospital, Seoul, South Korea. 2. Seoul Medical Center, Seoul, South Korea. 3. Asan Medical Center, Ulsan University School of Medicine, Seoul, South Korea. 4. Wonju College of Medicine, Yonsei University, Wonju, South Korea. 5. Bundang CHA Hospital, Seongnam, South Korea. 6. Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea. 7. Kangwon National University Hospital, Kangwon, South Korea. 8. Jeju National University Hospital, Jeju, South Korea. 9. Chung-Ang University Hospital, Seoul, South Korea. 10. Dong-A University Hospital, Busan, South Korea. 11. Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea. 12. Chungbuk National University Hospital, Cheongju, South Korea. 13. Daegu Catholic University Medical Center, Daegu, South Korea. 14. Chonnam National University Hospital, Gwangju, South Korea. 15. Korea University Anam Hospital, Seoul, South Korea. 16. Kyung Hee University Hospital, Seoul, South Korea. 17. Chungnam National University Hospital, Daejeon, South Korea. 18. College of Medicine, Hallym University, Seoul, South Korea. 19. Haeundae Paik Hospital, Busan, South Korea. 20. Pusan National University Hospital, Busan, South Korea. 21. Dongguk University Ilsan Hospital, Seoul, South Korea. 22. Korea University Guro Hospital, Seoul, South Korea. 23. Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea. Electronic address: parksmc@gmail.com.
Abstract
PURPOSE: The objective of this study was to evaluate the efficacy and tolerability of a triple combination of amlodipine/losartan/rosuvastatin in patients with hypertension and hypercholesterolemia. METHODS: A randomized, multicenter, double-blind, placebo-controlled study was conducted. Eligible patients with hypertension and a sitting diastolic blood pressure (SiDBP) of >90 mm Hg and LDL-C levels <250mg/dL were screened. After a 4-week run-in period with therapeutic lifestyle changes and losartan potassium 100mg once daily, patients who met both blood pressure criteria (80 mm Hg ≤ SiDBP < 110 mm Hg) and the LDL-C level criteria (defined in the National Cholesterol Education Program Adult Treatment Panel III cardiovascular risk categories) were randomized to 1 of 3 groups and treated once daily for 8 weeks: losartan potassium 100mg + rosuvastatin 20mg treatment (L/R 100/20) group, amlodipine camsylate 5mg + losartan potassium 100mg treatment (A/L 5/100) group, and amlodipine 5mg+ losartanpotassium 100mg + rosuvastatin 20mg (A/L/R 5/100/20) group. The primary efficacy variables were the percent change in LDL-C in the A/L/R 5/100/20 and A/L 5/100 groups and the mean change of SiDBP in the A/L/R 5/100/20 and L/R 100/20 groups after 8 weeks of treatment, relative to baseline values. FINDINGS: A total of 146 patients were enrolled and the demographic characteristics were similar among the 3 treatment groups. After 8 weeks of treatment, the mean (SD) percent change in LDL-C was significantly greater in the A/L/R group than in the A/L group (-48.40% [2.77%] vs -6.70% [3.00%]; P < 0.0001). Moreover, the mean change in SiDBP was significantly greater in the A/L/R group than in the L/R group (-9.75 [0.92] mm Hg vs -1.73 [1.03] mm Hg; P < 0.0001). SiDBPand LDL-C reductions in the A/L/R group were comparable to reductions in the A/L and L/R groups, respectively. Ten adverse events were reported in 7 patients (4.83%), and 1 patient from the A/L group (0.69%) experienced 2 adverse drug reactions (tachycardia and face edema), which were mild and resolved without specific treatment. There were no clinically significant tolerability issues during the treatment period. IMPLICATIONS: Triple combination therapy with amlodipine/losartan/rosuvastatin can be an effective therapeutic strategy in patients with hypertension combined with dyslipidemia. These findings will form the foundation of the future development of a single-pill triple combination. ClinicalTrials.gov identifier: NCT02899455.
RCT Entities:
PURPOSE: The objective of this study was to evaluate the efficacy and tolerability of a triple combination of amlodipine/losartan/rosuvastatin in patients with hypertension and hypercholesterolemia. METHODS: A randomized, multicenter, double-blind, placebo-controlled study was conducted. Eligible patients with hypertension and a sitting diastolic blood pressure (SiDBP) of >90 mm Hg and LDL-C levels <250mg/dL were screened. After a 4-week run-in period with therapeutic lifestyle changes and losartan potassium 100mg once daily, patients who met both blood pressure criteria (80 mm Hg ≤ SiDBP < 110 mm Hg) and the LDL-C level criteria (defined in the National Cholesterol Education Program Adult Treatment Panel III cardiovascular risk categories) were randomized to 1 of 3 groups and treated once daily for 8 weeks: losartan potassium 100mg + rosuvastatin 20mg treatment (L/R 100/20) group, amlodipine camsylate 5mg + losartan potassium 100mg treatment (A/L 5/100) group, and amlodipine 5mg+ losartan potassium 100mg + rosuvastatin 20mg (A/L/R 5/100/20) group. The primary efficacy variables were the percent change in LDL-C in the A/L/R 5/100/20 and A/L 5/100 groups and the mean change of SiDBP in the A/L/R 5/100/20 and L/R 100/20 groups after 8 weeks of treatment, relative to baseline values. FINDINGS: A total of 146 patients were enrolled and the demographic characteristics were similar among the 3 treatment groups. After 8 weeks of treatment, the mean (SD) percent change in LDL-C was significantly greater in the A/L/R group than in the A/L group (-48.40% [2.77%] vs -6.70% [3.00%]; P < 0.0001). Moreover, the mean change in SiDBP was significantly greater in the A/L/R group than in the L/R group (-9.75 [0.92] mm Hg vs -1.73 [1.03] mm Hg; P < 0.0001). SiDBP and LDL-C reductions in the A/L/R group were comparable to reductions in the A/L and L/R groups, respectively. Ten adverse events were reported in 7 patients (4.83%), and 1 patient from the A/L group (0.69%) experienced 2 adverse drug reactions (tachycardia and face edema), which were mild and resolved without specific treatment. There were no clinically significant tolerability issues during the treatment period. IMPLICATIONS: Triple combination therapy with amlodipine/losartan/rosuvastatin can be an effective therapeutic strategy in patients with hypertension combined with dyslipidemia. These findings will form the foundation of the future development of a single-pill triple combination. ClinicalTrials.gov identifier: NCT02899455.