Efficacy and safety of early versus late titration of fixed-dose irbesartan/hydrochlorothiazide: ACTUAL study

Figures & data

Figure 1. Study design. HTN, hypertension; V, visit; W, week; R, randomized.

Table I. Baseline and demographic characteristics of the intent-to-treat population.

Parameter	Late titration group, n = 405	Early titration group, n = 390	All, n = 795
Age in years, mean (SD)	57.60 (11.79)	57.89 (12.08)	57.74 (11.93)
Males, n (%)	152 (37.5)	168 (43.1)	320 (40.3)
Weight in kg, mean (SD)	77.45 (16.92)	79.02 (15.65)	78.22 (16.32)
BMI in kg/m^2, mean (SD)	29.44 (4.85)	29.87 (5.17)	29.65 (5.01)
WC in cm, mean (SD)	99.47 (12.48)	100.83 (13.33)	100.13 (12.91)
Abdominal obesity, n (%)	278 (69.2)	251 (65.0)	529 (67.1)
Vital signs
Systolic BP in mmHg, mean (SD)	162.44 (8.97)	162.12 (9.16)	162.28 (9.06)
Diastolic BP in mmHg, mean (SD)	95.87 (8.20)	95.00 (8.99)	95.44 (8.60)
Heart rate in beats/min, mean (SD)	75.92 (11.56)	75.31 (11.33)	75.62 (11.44)
Cardiovascular risk factors and comorbidities, n (%)
Angina	13 (3.2)	15 (3.8)	28 (3.5)
Atrial fibrillation/flutter	6 (1.5)	5 (1.3)	11 (1.4)
Current smoking (≥5 cigarettes/day, ≥6 months)	32 (7.9)	21 (5.4)	53 (6.7)
Dyslipidemia	121 (29.9)	114 (29.2)	235 (29.6)
Myocardial infarction	5 (1.2)	4 (1.0)	9 (1.1)
Peripheral arterial disease	5 (1.2)	5 (1.3)	10 (1.3)
Stroke/transient ischemic attack	11 (2.7)	14 (3.6)	25 (3.1)
Type 2 diabetes	83 (20.5)	95 (24.4)	178 (22.4)
Previous antihypertensive treatment, n (%)
ACE inhibitors	146 (36.0)	155 (39.7)	301 (37.9)
Angiotensin II receptor blocker	99 (24.4)	78 (20.0)	177 (22.3)
Calcium-channel blocker	77 (19.0)	75 (19.2)	152 (19.1)
Beta blocker	64 (15.8)	56 (14.4)	120 (15.1)
Diuretic	17 (4.2)	23 (5.9)	40 (5.0)
Renin inhibitor	0 (0.0)	1 (0.3)	1 (0.1)
Others	1 (0.2)	1 (0.3)	2 (0.3)
Missing	1 (0.2)	1 (0.3)	2 (0.3)

SD, standard deviation; BMI, body mass index; WC, waist circumference; BP, blood pressure; ACE, angiotensin converting enzyme.

Table II. Change in BP (ANCOVA model) from baseline in the intent-to-treat population.

Parameter	Late titration group, n = 405	Early titration group, n = 390	Adjusted means of estimated BP difference between early and late titration groups	p-value (ANCOVA)
SBP change from W0 to W6 (LOCF)	−26.34 (17.37)	−28.78 (15.45)	−2.50	0.0204
DBP change from W0 to W6 (LOCF)	−11.68 (10.32)	−13.43 (10.38)	−2.20	0.0004
SBP change from W0 to W10 (LOCF)	−31.02 (16.15 )	−29.51 (15.80)	1.48	0.1423
DBP change from W0 to W10 (LOCF)	−14.46 (10.18)	−14.12 (10.06)	−0.12	0.8313

BP, blood pressure; ANCOVA, analysis of covariance; SBP, systolic blood pressure; W0, week 0; W6, week 6; LOCF, last observation carried forward; DBP, diastolic blood pressure; W10, week 10. Adjusted means difference=Adjusted mean SBP or DBP change for early titration–Adjusted mean SBP or DBP change for late titration. The following factors were included in the model: treatment group, SBP or DBP at W0, pulse pressure at W0 in class and the region as fixed effects, and the centre as random effect.

Table III. BP control at week 6 and week 10 in the intent-to-treat population.

Parameter	Controlled patients in the late titration group, n = 405	Controlled patients in the early titration group, n = 390	Odds ratio	95% Wald confidence interval	p-value
At W6, n (%)
All patients^a	229 (56.5)	255 (65.4)	1.451	(1.081–1.947)	0.0132
Taking BP goal for diabetes into account^b	208 (51.4)	214 (54.9)	1.149	(0.866–1.525)	0.3350
Controlled patients at W10, n (%)
All patients^a	287 (70.9)	258 (66.2)	0.774	(0.568–1.057)	0.1068
Taking BP goal for diabetes into account^b	259 (64.0)	225 (57.7)	0.757	(0.566–1.012)	0.0600

BP, blood pressure; W6, week 6; W10, week 10. ^aAll patients’ BP goal: SBP < 140 mmHg and DBP < 90 mmHg. ^bPatients without diabetes BP goal: SBP < 140 mmHg and DBP < 90 mmHg; patients with diabetes BP goal : SBP < 130 mmHg and DBP < 80 mmHg.

Figure 2. Treatment-related adverse events by system organ class and preferred term according to randomization group – safety population. *One patient with missing randomization group. TRAE, treatment-related adverse events.