Efficacy and safety of fixed-dose combination therapy with olmesartan medoxomil and rosuvastatin in Korean patients with mild to moderate hypertension and dyslipidemia: an 8-week, multicenter, randomized, double-blind, factorial-design study (OLSTA-D RCT: OLmesartan rosuvaSTAtin from Daewoong)

Figures & data

Table 1 Inclusion criteria according to risk factors and a 10-year risk assessment

Category		LDL-C level (mg/dL)	DBP (mmHg)
1.	Person without risk factorsa other than hypertension and dyslipidemia	160–250	90–109 (patients with DM, CKD: 80–99)
2.	Person with more than one risk factora other than hypertension and dyslipidemia and with a <10% risk in the 10-year risk assessment	160–250
3.	Person with more than one risk factora other than hypertension and dyslipidemia and with a 10%–20% risk in the 10-year risk assessment	130–250
4.	Person with coronary heart disease or equivalentb or with a >20% risk in the 10-year risk assessment	100–250

Notes:

a Risk factors: a) Cigarette smoking; b) HDL-C level <40 mg/dL; c) family history of premature coronary heart disease (male first degree relative <55 years; female first degree relative <65 years); and d) age (males ≥45 years; females ≥55 years). HDL-C level ≥60 mg/dL counts as a “negative” risk factor; its presence excludes one risk factor from the total count.

b Patients with carotid artery disease, peripheral vascular disease, abdominal aortic aneurysm, and type 2 DM.

Abbreviations: CKD, chronic kidney disease; DBP, diastolic blood pressure; DM, diabetes mellitus; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.

Figure 1 Study flowchart.

Abbreviations: BP, blood pressure; FAS, full analysis set; FDC, fixed dose combination; IP, investigational product; SAEs, serious adverse events.

Table 2 Demographics and baseline characteristics prior to randomization in the full analysis set

Characteristic*	FDC therapy group (n=61)	Olmesartan medoxomil group (n=36)	Rosuvastatin group (n=36)	Placebo group (n=29)	Total (n=162)
Age (years)	61.9 (8.1)	59.5 (6.9)	61.8 (8.0)	62.5 (8.2)	61.4 (7.8)
Height (cm)	162.8 (8.6)	163.7 (7.0)	163.9 (8.4)	165.2 (8.6)	163.7 (8.2)
Weight (kg)	67.5 (9.3)	69.0 (9.3)	69.1 (11.7)	67.4 (9.9)	68.2 (10.0)
BMI (kg/m^2)	25.4 (2.4)	25.7 (2.6)	25.6 (3.0)	24.7 (2.8)	25.4 (2.7)
Sex, n (%)
Male	34 (55.7)	24 (66.7)	25 (69.4)	21 (72.4)	104 (64.2)
Female	27 (44.3)	12 (33.3)	11 (30.6)	8 (27.6)	58 (35.8)
Lipid parameters (mg/dL)
LDL-C	154.4 (32.2)	156.7 (34.5)	154.0 (28.2)	152.5 (32.7)	154.5 (31.7)
HDL-C	48.9 (10.8)	52.1 (12.3)	50.7 (12.0)	48.6 (11.1)	50.0 (11.4)
Triglyceride	152.3 (72.4)	145.6 (58.1)	132.3 (54.9)	160.0 (79.1)	147.7 (67.2)
Total cholesterol	230.5 (37.6)	233.3 (38.3)	227.4 (32.3)	228.9 (37.0)	230.2 (36.3)
Blood pressure (mmHg)
Systolic	150.6 (11.9)	150.6 (15.5)	148.9 (13.3)	152.2 (14.5)	150.5 (13.5)
Diastolic	92.0 (7.4)	93.3 (5.0)	92.9 (6.5)	92.5 (7.0)	92.6 (6.6)
Concurrent history, n (%)
Diabetes mellitus
Yes	27 (44.3)	14 (38.9)	8 (22.2)	9 (31.0)	58 (35.8)
No	34 (55.7)	22 (61.1)	28 (77.8)	20 (69.0)	104 (64.2)
Chronic kidney disease
Yes	1 (1.6)	1 (2.8)	3 (8.3)	2 (6.9)	7 (4.3)
No	60 (98.4)	35 (97.2)	33 (91.7)	27 (93.1)	155 (95.7)
Smoking status, n (%)
Nonsmoker	40 (65.6)	22 (61.1)	20 (55.6)	13 (44.8)	95 (58.6)
Current smoker	8 (13.1)	5 (13.9)	7 (19.4)	6 (20.7)	26 (16.1)
Ex-smoker	13 (21.3)	9 (25.0)	9 (25.0)	10 (34.5)	41 (25.3)
Family history of early CHD, n (%)
Yes	2 (3.3)	3 (8.3)	7 (19.4)	0 (0.0)	12 (7.4)
No	59 (96.7)	33 (91.7)	29 (80.6)	29 (100.0)	150 (92.6)

Notes: Data are presented as mean (standard deviation) unless otherwise specified.

* There were no significant differences among the treatment groups except for family history of early CHD.

Abbreviations: BMI, body mass index; CHD, coronary heart disease; FDC, fixed-dose combination; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.

Table 3 Changes in the low-density lipoprotein cholesterol level at weeks 4 and 8 in the full analysis set

	FDC therapy group (n=61)	Olmesartan medoxomil group (n=36)	Rosuvastatin group (n=36)	Placebo group (n=29)
Week 4
Mean (SD), mg/dL	74.6 (32.0)	153.3 (40.3)	80.2 (27.2)	140.0 (45.9)
LS mean percent change from baseline (SE), %	−51.2 (2.8)	−1.2 (3.4)	−47.8 (3.5)	−7.8 (3.8)
LS mean difference, % (SE) (95% CI)	–	−50.0 (4.1) (−58.0 to 42.0)	−3.4 (4.1) (−11.4 to 4.6)	−43.4 (4.4) (−52.0 to 43.8)
P-value* vs FDC therapy	–	<0.0001	0.4034	<0.0001
Week 8
Mean (SD), mg/dL	72.4 (27.2)	153.5 (40.6)	80.7 (34.5)	146.7 (48.6)
LS mean percentage change from baseline (SE), %	−52.3 (2.8)	−0.6 (3.5)	−46.9 (3.5)	−3.2 (3.9)
LS mean difference, % (SE) (95% CI)	–	−51.7 (4.1) (−59.8 to −43.6)	−5.4 (4.1) (−13.5 to 2.7)	−49.1 (4.4) (−57.8 to −40.4)
P-value* vs FDC therapy	–	<0.0001	0.1864	<0.0001

Note:

* Analysis of covariance.

Abbreviations: CI, confidence interval; FDC, fixed-dose combination; LS, least square; SD, standard deviation; SE, standard error.

Table 4 Least square mean percentage change from baseline in the total cholesterol, triglyceride and high-density lipoprotein cholesterol levels at weeks 4 and 8 in the full analysis set

Parameter	FDC therapy group (n=61)	Olmesartan medoxomil group (n=36)	Rosuvastatin group (n=36)	Placebo group (n=29)
Week 4
Total cholesterol, LS mean percent change from baseline (SE), %	−36.1 (1.9)	−1.1 (2.4)	−33.9 (2.4)	−3.5 (2.6)
LS mean difference, % (SE) (95% CI)	–	−35.0* (2.8) (−40.6 to 29.4)	−2.23*** (2.8) (−7.8 to 3.3)	−32.6* (3.3) (−38.6 to 26.6)
Triglyceride LS mean percent change from baseline (SE), %	−15.5 (5.6)	9.5 (7.0)	−8.7 (7.2)	15.7 (7.9)
LS mean difference, % (SE) (95% CI)	–	−25.0** (8.6) (−42.0 to 8.1)	−6.8*** (8.6) (−23.9 to 10.3)	−31.2** (9.2) (−49.5 to 13.0)
HDL-C, LS mean percent change from baseline (SE), %	8.0 (2.1)	1.1 (2.7)	5.8 (2.7)	6.2 (3.0)
LS mean difference, % (SE) (95% CI)	–	6.9** (3.3) (0.5 to 13.3)	2.2*** (3.3) (−4.2 to 8.6)	1.8*** (3.5) (−5.1 to 8.6)
Week 8
Total cholesterol, LS mean percent change from baseline (SE), %	−37.1 (2.0)	−0.7 (2.5)	−32.8 (2.6)	−2.4 (2.8)
LS mean difference, % (SE) (95% CI)		−36.4* (3.0) (−42.3 to 30.1)	−4.35*** (3.0) (−10.3 to 1.6)	−34.7* (3.2) (−41.1 to 28.4)
Triglyceride, LS mean percent change from baseline (SE), %	−13.7 (6.4)	17.8 (8.0)	−8.1 (8.2)	0.9 (9.0)
LS mean difference, % (SE) (95% CI)		−31.4** (9.7) (−50.6 to 12.2)	−5.6*** (9.8) (−24.9 to 13.7)	−14.6*** (10.4) (−35.2 to 6.1)
HDL-C, LS mean percent change from baseline (SE), %	6.9 (2.2)	−1.2 (2.8)	5.3 (2.8)	9.7 (3.1)
LS mean difference, % (SE) (95% CI)		8.1** (3.4) (1.4 to 14.8)	1.5*** (3.4) (−5.6 to 8.2)	−2.8*** (3.6) (−10.0 to 4.4)

Notes:

* P<0.0001;

** P<0.05;

*** P>0.05 (analysis of covariance) vs FDC therapy.

Abbreviations: CI, confidence interval; FDC, fixed-dose combination; HDL-C, high-density lipoprotein cholesterol; LS, least square; SE, standard error.

Figure 2 Percentage of patients who achieved the treatment goals of low-density lipoprotein cholesterol levels and blood pressure at week 8 in the full analysis set.

Notes: (A) Percentage of patient who achieved the treatment goal of low-density lipoprotein cholesterol levels defined by the National Cholesterol Education Program Adult Treatment Panel III. Goal was defined as low-density lipoprotein cholesterol level <100, 130, or 160 mg/dL depending on the risk profile. (B) Percentage of patients who achieved the treatment goal of blood pressure defined by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Goal was defined as DBP <90 mmHg (or <80 mmHg in patients with diabetes mellitus or chronic kidney disease).
Abbreviations: DBP, diastolic blood pressure; FDC, fixed-dose combination.

Table 5 Changes in blood pressure at weeks 4 and 8 in the full analysis set

	FDC therapy group (n=61)	Olmesartan medoxomil group (n=36)	Rosuvastatin group (n=36)	Placebo group (n=29)
Diastolic blood pressure
Week 4
Mean (SD), mmHg	84.8 (8.5)	86.0 (7.9)	90.9 (7.0)	92.7 (8.6)
LS mean change from baseline (SE), mmHg	−7.4 (1.1)	−6.7 (1.4)	−1.6 (1.4)	0.4 (1.5)
LS mean difference, mmHg (SE) (95% CI)	–	−0.7 (1.6) (−3.9 to 2.5)	−5.7 (1.6) (−9.0 to −2.5)	−7.7 (1.8) (−11.2 to 4.3)
P-value* vs FDC therapy	–	0.6695	0.0006	<0.0001
Week 8
Mean (SD), mmHg	82.1 (9.8)	85.0 (8.3)	93.0 (9.2)	92.9 (8.7)
LS mean change from baseline (SE), mmHg	−10.4 (1.2)	−8.1 (1.5)	0.1 (1.6)	0.2 (1.7)
LS mean difference, mmHg (SE) (95% CI)	–	−2.3 (1.8) (−5.9 to 1.3)	−10.5 (1.8) (−14.1 to −6.9)	−10.5 (2.0) (−14.4 to −6.7)
P-value* vs FDC therapy	–	0.2096	<0.0001	<0.0001
Systolic blood pressure
Week 4
Mean (SD), mmHg	135.6 (14.8)	133.9 (13.5)	150.2 (17.1)	151.5 (18.3)
LS mean change from baseline (SE), mmHg	−14.8 (2.1)	−16.5 (2.6)	0.4 (2.6)	0.2 (2.9)
LS mean difference, mmHg (SE) (95% CI)	–	1.6 (3.1) (−4.5 to 7.8)	−15.3 (3.1) (−21.4 to −9.1)	−15.1 (3.3) (−21.7 to −8.5)
P-value* vs FDC therapy	–	0.5996	<0.0001	<0.0001
Week 8
Mean (SD), mmHg	132.6 (17.9)	133.4 (14.5)	153.4 (19.1)	154.2 (21.0)
LS mean change from baseline (SE), mmHg	−18.7 (2.3)	−17.9 (2.9)	2.9 (2.9)	1.75 (3.3)
LS mean difference, mmHg (SE) (95% CI)	–	−0.8 (3.5) (−7.8 to 6.1)	−21.6 (3.5) (−28.5 to −14.7)	−20.4 (3.8) (−27.9 to −13.0)
P-value* vs FDC therapy	–	0.8147	<0.0001	<0.0001

Note:

* Analysis of covariance.

Abbreviations: CI, confidence interval; FDC, fixed-dose combination; LS, least square; SD, standard deviation; SE, standard error.

Table 6 Summary of AEs and adverse drug reactions in the safety set

	FDC therapy group (n=71)	Olmesartan medoxomil group (n=38)	Rosuvastatin group (n=38)	Placebo group (n=34)	Total (N=181)
Number of patients with AEs*	17 (23.9) [23]	7 (18.4) [7]	9 (23.7) [11]	8 (23.5) [9]	41 (22.7) [50]
P-value					0.9202**
Severity, number of AEs
Mild	18	4	8	7	37
Moderate	5	3	3	2	13
Severe	0	0	0	0	0
Number of patients with SAEs (%)	0	1 (2.6)	1 (2.6)	0	2 (1.1)
P-value					0.3680**
Adverse drug reactions*	2 (2.8) [4]	0	2 (5.3) [3]	1 (2.9) [1]	5 (2.8) [8]
P-value					0.5990**
ALT increased	1 (1.4) [1]		0	0	1 (0.6) [1]
AST increased	1 (1.4) [1]		0	0	1 (0.6) [1]
Blood creatinine increased	1 (1.4) [1]		0	0	1 (0.6) [1]
Ccr decreased	1 (1.4) [1]		0	0	1 (0.6) [1]
Blood triglycerides increased	0		0	1 (2.9) [1]	1 (0.6) [1]
Headache	0		2 (5.3) [2]	0	2 (1.1) [2]
Insomnia	0		1 (2.6) [1]	0	1 (0.6) [1]

Notes:

* Data are presented as number of patients (%) [number of events] and the denominator for % is the number of patients in the column.

** Chi-square or Fisher’s exact test.

Abbreviations: AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; Ccr, creatinine clearance; FDC, fixed-dose combination; SAEs, serious adverse events.

Table S1 Twenty-five participating institutions

Number	Site location
1	Ajou University Medical Center, Suwon, Korea
2	Busan Paik Hospital, Busan, Korea
3	Chonnam National University Hospital, Gwangju, Korea
4	Chungnam National University Hospital, Daejeon, Korea
5	Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea
6	Dankook University Hospital, Cheonan, Korea
7	Dong-A University Hospital, Busan, Korea
8	Gachon University Gil Hospital, Incheon, Korea
9	Inha University College of Medicine, Incheon, Korea
10	Kangdong Sacred Heart Hospital, Seoul, Korea
11	Keimyung University Dongsan Medical Center, Daegu, Korea
12	Korea University Anam Hospital, Seoul, Korea
13	Korea University Guro Hospital, Seoul, Korea
14	Pusan National University Hospital, Busan, Korea
15	Samsung Medical Center, Seoul, Korea
16	Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
17	Seoul National University Bundang Hospital, Seongnam, Korea
18	Seoul National University Hospital, Seoul, Korea
19	Seoul St Mary’s Hospital, Seoul, Korea
20	Soonchunhyang University Hospital, Seoul, Korea
21	Ulsan University Hospital, Ulsan, Korea
22	Wonkwang University Hospital, Iksan, Korea
23	Yeungnam University Medical Center, Daegu, Korea
24	Yonsei University Gangnam Severance Hospital, Seoul, Korea
25	Yonsei University Severance Hospital, Seoul, Korea