Efficacy and Safety of a Fixed-Dose Combination of Candesartan and Rosuvastatin on Blood Pressure and Cholesterol in Patients With Hypertension and Hypercholesterolemia: A Multicenter, Randomized, Double-Blind, Parallel Phase III Clinical Study

Kyoung Im Cho, Bo Hyun Kim, Yong Hyun Park, Jeong Cheon Ahn, Sang Hyun Kim, Wook Jin Chung, Weon Kim, Il Suk Sohn, Jin Ho Shin, Yong Jin Kim, K. Chang, Cheol Woong Yu, Soe Hee Ahn, Seok Yeon Kim, Jae Kean Ryu, Jong Young Lee, Bum Kee Hong, Taek Jong Hong, C. Gyu Park

Research output: Contribution to journalArticle

Abstract

Purpose: The aim of this study was to evaluate the blood pressure–lowering and cholesterol-lowering effects of a fixed-dose combination therapy using candesartan (CND)/rosuvastatin (RSV) compared with CND or RSV monotherapy in patients with hypertension and hypercholesterolemia. Methods: This study was a 12-week, randomized, double-blind, placebo-controlled, multicenter study. A total of 394 patients were screened. After a 4-week run-in period, 219 of these patients with hypertension and primary hypercholesterolemia were randomized. Patients received 1 of 3 regimens for 8 weeks: (1) CND 32 mg/RSV 20 mg, (2) RSV 20 mg, or (3) CND 32 mg. The primary outcome variables were changes in the systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the percentage changes in LDL-C from baseline to the drug treatment at 8 weeks. The secondary outcome variables were percentage changes of total cholesterol, triglycerides, HDL-C, non–HDL-C, apolipoprotein B, apolipoprotein A-I, high-sensitivity C-reactive protein, and glucose metabolic indices, including percentage changes of the homeostasis model assessment of insulin resistance (HOMA-IR), adiponectin, and hemoglobin A1c. Tolerability of combination therapy was compared with other monotherapy groups. Findings: The percentage changes of LDL-C were −48.6% (from 157.2 to 80.1 mg/dL) in the RSV group and −49.8% (from 160.2 to 78.9 mg/dL) in the CND/RSV group from baseline to the end of 8 weeks of treatment. Mean SBP and DBP were significantly decreased in the CND/RSV and CND groups after 8 weeks (P < 0.001 for all); however, no significant differences were found between the 2 groups. Total cholesterol levels, triglycerides, non–HDL-C, and apolipoprotein B were significantly reduced in the CND/RSV and RSV groups, with no significant differences between the groups compared with the CND group (P < 0.001 for all). The percentage changes of HOMA-IR, adiponectin, and hemoglobin A1c had no significant differences between the combination groups and monotherapy groups. However, in a 2-sample t test, HOMA-IR was significantly decreased in the CND/RSV group compared with the RSV group in nondiabetic patients (mean [SD] percentage change of HOMA-IR, −8.7% [37.6%] vs 17.1% [53.1%]; P = 0.048). There were no significant differences in metabolic indices between the diabetic groups. Adverse events in the CND/RSV group were similar to those in the monotherapy group. Implications: Once-daily fixed-dose combination therapy with CND/RSV is an effective, tolerable, convenient treatment option for patients with essential hypertension and hypercholesteremia. ClinicalTrials.gov identifier: NCT02770261. (Clin Ther. 2019;XX:XXX–XXX)

Original languageEnglish
JournalClinical Therapeutics
DOIs
Publication statusPublished - 2019 Jan 1

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Hypercholesterolemia
Cholesterol
Blood Pressure
Hypertension
Safety
Insulin Resistance
Homeostasis
Adiponectin
Apolipoproteins B
candesartan
Rosuvastatin Calcium
Clinical Studies
Hemoglobins
Triglycerides
Therapeutics
Apolipoprotein A-I
C-Reactive Protein
HDL Cholesterol
Multicenter Studies
Placebos

Keywords

  • candesartan
  • drug combination
  • dyslipidemia
  • hypertension
  • rosuvastatin calcium

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Efficacy and Safety of a Fixed-Dose Combination of Candesartan and Rosuvastatin on Blood Pressure and Cholesterol in Patients With Hypertension and Hypercholesterolemia : A Multicenter, Randomized, Double-Blind, Parallel Phase III Clinical Study. / Cho, Kyoung Im; Kim, Bo Hyun; Park, Yong Hyun; Ahn, Jeong Cheon; Kim, Sang Hyun; Chung, Wook Jin; Kim, Weon; Sohn, Il Suk; Shin, Jin Ho; Kim, Yong Jin; Chang, K.; Yu, Cheol Woong; Ahn, Soe Hee; Kim, Seok Yeon; Ryu, Jae Kean; Lee, Jong Young; Hong, Bum Kee; Hong, Taek Jong; Gyu Park, C.

In: Clinical Therapeutics, 01.01.2019.

Research output: Contribution to journalArticle

Cho, Kyoung Im ; Kim, Bo Hyun ; Park, Yong Hyun ; Ahn, Jeong Cheon ; Kim, Sang Hyun ; Chung, Wook Jin ; Kim, Weon ; Sohn, Il Suk ; Shin, Jin Ho ; Kim, Yong Jin ; Chang, K. ; Yu, Cheol Woong ; Ahn, Soe Hee ; Kim, Seok Yeon ; Ryu, Jae Kean ; Lee, Jong Young ; Hong, Bum Kee ; Hong, Taek Jong ; Gyu Park, C. / Efficacy and Safety of a Fixed-Dose Combination of Candesartan and Rosuvastatin on Blood Pressure and Cholesterol in Patients With Hypertension and Hypercholesterolemia : A Multicenter, Randomized, Double-Blind, Parallel Phase III Clinical Study. In: Clinical Therapeutics. 2019.
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abstract = "Purpose: The aim of this study was to evaluate the blood pressure–lowering and cholesterol-lowering effects of a fixed-dose combination therapy using candesartan (CND)/rosuvastatin (RSV) compared with CND or RSV monotherapy in patients with hypertension and hypercholesterolemia. Methods: This study was a 12-week, randomized, double-blind, placebo-controlled, multicenter study. A total of 394 patients were screened. After a 4-week run-in period, 219 of these patients with hypertension and primary hypercholesterolemia were randomized. Patients received 1 of 3 regimens for 8 weeks: (1) CND 32 mg/RSV 20 mg, (2) RSV 20 mg, or (3) CND 32 mg. The primary outcome variables were changes in the systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the percentage changes in LDL-C from baseline to the drug treatment at 8 weeks. The secondary outcome variables were percentage changes of total cholesterol, triglycerides, HDL-C, non–HDL-C, apolipoprotein B, apolipoprotein A-I, high-sensitivity C-reactive protein, and glucose metabolic indices, including percentage changes of the homeostasis model assessment of insulin resistance (HOMA-IR), adiponectin, and hemoglobin A1c. Tolerability of combination therapy was compared with other monotherapy groups. Findings: The percentage changes of LDL-C were −48.6{\%} (from 157.2 to 80.1 mg/dL) in the RSV group and −49.8{\%} (from 160.2 to 78.9 mg/dL) in the CND/RSV group from baseline to the end of 8 weeks of treatment. Mean SBP and DBP were significantly decreased in the CND/RSV and CND groups after 8 weeks (P < 0.001 for all); however, no significant differences were found between the 2 groups. Total cholesterol levels, triglycerides, non–HDL-C, and apolipoprotein B were significantly reduced in the CND/RSV and RSV groups, with no significant differences between the groups compared with the CND group (P < 0.001 for all). The percentage changes of HOMA-IR, adiponectin, and hemoglobin A1c had no significant differences between the combination groups and monotherapy groups. However, in a 2-sample t test, HOMA-IR was significantly decreased in the CND/RSV group compared with the RSV group in nondiabetic patients (mean [SD] percentage change of HOMA-IR, −8.7{\%} [37.6{\%}] vs 17.1{\%} [53.1{\%}]; P = 0.048). There were no significant differences in metabolic indices between the diabetic groups. Adverse events in the CND/RSV group were similar to those in the monotherapy group. Implications: Once-daily fixed-dose combination therapy with CND/RSV is an effective, tolerable, convenient treatment option for patients with essential hypertension and hypercholesteremia. ClinicalTrials.gov identifier: NCT02770261. (Clin Ther. 2019;XX:XXX–XXX)",
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TY - JOUR

T1 - Efficacy and Safety of a Fixed-Dose Combination of Candesartan and Rosuvastatin on Blood Pressure and Cholesterol in Patients With Hypertension and Hypercholesterolemia

T2 - A Multicenter, Randomized, Double-Blind, Parallel Phase III Clinical Study

AU - Cho, Kyoung Im

AU - Kim, Bo Hyun

AU - Park, Yong Hyun

AU - Ahn, Jeong Cheon

AU - Kim, Sang Hyun

AU - Chung, Wook Jin

AU - Kim, Weon

AU - Sohn, Il Suk

AU - Shin, Jin Ho

AU - Kim, Yong Jin

AU - Chang, K.

AU - Yu, Cheol Woong

AU - Ahn, Soe Hee

AU - Kim, Seok Yeon

AU - Ryu, Jae Kean

AU - Lee, Jong Young

AU - Hong, Bum Kee

AU - Hong, Taek Jong

AU - Gyu Park, C.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Purpose: The aim of this study was to evaluate the blood pressure–lowering and cholesterol-lowering effects of a fixed-dose combination therapy using candesartan (CND)/rosuvastatin (RSV) compared with CND or RSV monotherapy in patients with hypertension and hypercholesterolemia. Methods: This study was a 12-week, randomized, double-blind, placebo-controlled, multicenter study. A total of 394 patients were screened. After a 4-week run-in period, 219 of these patients with hypertension and primary hypercholesterolemia were randomized. Patients received 1 of 3 regimens for 8 weeks: (1) CND 32 mg/RSV 20 mg, (2) RSV 20 mg, or (3) CND 32 mg. The primary outcome variables were changes in the systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the percentage changes in LDL-C from baseline to the drug treatment at 8 weeks. The secondary outcome variables were percentage changes of total cholesterol, triglycerides, HDL-C, non–HDL-C, apolipoprotein B, apolipoprotein A-I, high-sensitivity C-reactive protein, and glucose metabolic indices, including percentage changes of the homeostasis model assessment of insulin resistance (HOMA-IR), adiponectin, and hemoglobin A1c. Tolerability of combination therapy was compared with other monotherapy groups. Findings: The percentage changes of LDL-C were −48.6% (from 157.2 to 80.1 mg/dL) in the RSV group and −49.8% (from 160.2 to 78.9 mg/dL) in the CND/RSV group from baseline to the end of 8 weeks of treatment. Mean SBP and DBP were significantly decreased in the CND/RSV and CND groups after 8 weeks (P < 0.001 for all); however, no significant differences were found between the 2 groups. Total cholesterol levels, triglycerides, non–HDL-C, and apolipoprotein B were significantly reduced in the CND/RSV and RSV groups, with no significant differences between the groups compared with the CND group (P < 0.001 for all). The percentage changes of HOMA-IR, adiponectin, and hemoglobin A1c had no significant differences between the combination groups and monotherapy groups. However, in a 2-sample t test, HOMA-IR was significantly decreased in the CND/RSV group compared with the RSV group in nondiabetic patients (mean [SD] percentage change of HOMA-IR, −8.7% [37.6%] vs 17.1% [53.1%]; P = 0.048). There were no significant differences in metabolic indices between the diabetic groups. Adverse events in the CND/RSV group were similar to those in the monotherapy group. Implications: Once-daily fixed-dose combination therapy with CND/RSV is an effective, tolerable, convenient treatment option for patients with essential hypertension and hypercholesteremia. ClinicalTrials.gov identifier: NCT02770261. (Clin Ther. 2019;XX:XXX–XXX)

AB - Purpose: The aim of this study was to evaluate the blood pressure–lowering and cholesterol-lowering effects of a fixed-dose combination therapy using candesartan (CND)/rosuvastatin (RSV) compared with CND or RSV monotherapy in patients with hypertension and hypercholesterolemia. Methods: This study was a 12-week, randomized, double-blind, placebo-controlled, multicenter study. A total of 394 patients were screened. After a 4-week run-in period, 219 of these patients with hypertension and primary hypercholesterolemia were randomized. Patients received 1 of 3 regimens for 8 weeks: (1) CND 32 mg/RSV 20 mg, (2) RSV 20 mg, or (3) CND 32 mg. The primary outcome variables were changes in the systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the percentage changes in LDL-C from baseline to the drug treatment at 8 weeks. The secondary outcome variables were percentage changes of total cholesterol, triglycerides, HDL-C, non–HDL-C, apolipoprotein B, apolipoprotein A-I, high-sensitivity C-reactive protein, and glucose metabolic indices, including percentage changes of the homeostasis model assessment of insulin resistance (HOMA-IR), adiponectin, and hemoglobin A1c. Tolerability of combination therapy was compared with other monotherapy groups. Findings: The percentage changes of LDL-C were −48.6% (from 157.2 to 80.1 mg/dL) in the RSV group and −49.8% (from 160.2 to 78.9 mg/dL) in the CND/RSV group from baseline to the end of 8 weeks of treatment. Mean SBP and DBP were significantly decreased in the CND/RSV and CND groups after 8 weeks (P < 0.001 for all); however, no significant differences were found between the 2 groups. Total cholesterol levels, triglycerides, non–HDL-C, and apolipoprotein B were significantly reduced in the CND/RSV and RSV groups, with no significant differences between the groups compared with the CND group (P < 0.001 for all). The percentage changes of HOMA-IR, adiponectin, and hemoglobin A1c had no significant differences between the combination groups and monotherapy groups. However, in a 2-sample t test, HOMA-IR was significantly decreased in the CND/RSV group compared with the RSV group in nondiabetic patients (mean [SD] percentage change of HOMA-IR, −8.7% [37.6%] vs 17.1% [53.1%]; P = 0.048). There were no significant differences in metabolic indices between the diabetic groups. Adverse events in the CND/RSV group were similar to those in the monotherapy group. Implications: Once-daily fixed-dose combination therapy with CND/RSV is an effective, tolerable, convenient treatment option for patients with essential hypertension and hypercholesteremia. ClinicalTrials.gov identifier: NCT02770261. (Clin Ther. 2019;XX:XXX–XXX)

KW - candesartan

KW - drug combination

KW - dyslipidemia

KW - hypertension

KW - rosuvastatin calcium

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