A phase III, open-label, multicenter study to evaluate the safety and efficacy of long-term triple combination therapy with azilsartan, amlodipine, and hydrochlorothiazide in patients with essential hypertension

Figures & data

Figure 1. Study design. *RAS inhibitors (ACE inhibitors, ARBs, direct renin inhibitors), CCBs, thiazide diuretics, and diuretics similar to thiazides.

Figure 2. Patient disposition throughout the study.

Table 1. Baseline characteristics of all randomized patients.

	Total (n = 341)
Mean age, years (SD)	60.8 (11.44)
Gender, n (%)
Male	244 (71.6)
Female	97 (28.4)
BMI at Week 0, kg/m^2 (SD)	26.20 (3.883)
Smoking status, n (%)
Never smoker	116 (34.0)
Current smoker	84 (24.6)
Former smoker	141 (41.3)
History of alcohol consumption, n (%)	120 (35.2)
Mean duration of hypertension, years (SD)	9.42 (7.73)
Concurrent diabetes mellitus, n (%)	90 (26.4)
Concurrent chronic kidney disease, n (%)	65 (19.1)
Mean office sitting SBP at Week 0, mmHg (SD)	143.7 (8.23)
Mean office sitting DBP at Week 0, mmHg (SD)	86.2 (9.28)
Mean home sitting SBP at Week 0, mmHg (SD)	144.3 (13.60)
Mean home sitting DBP at Week 0, mmHg (SD)	88.9 (9.54)
Mean eGFRcreat^a at Week 0, mL/min/1.73m^2 (SD)	78.1 (16.73)
Concurrent medical conditions, n (%)	313 (91.8)
Cerebrovascular disorder	2 (0.6)
Cardiac disease	11 (3.2)
Vascular disorder	21 (6.2)
Hepatic disorder	43 (12.6)
Dyslipidaemia	174 (51.0)
Other	292 (85.6)
History of antihypertensive medication, n (%)	338 (99.1)
ARBs	310 (90.9)
ACE inhibitors	9 (2.6)
CCBs	313 (91.8)
Diuretics	66 (19.4)
Beta-blockers	19 (5.6)
Other	14 (4.1)

^a Male eGFRcreat in mL/min/1.73m² = 194 × Cr (mg/dL)^−1.094 × age (years)^−0.287.

Female eGFRcreat in mL/min/1.73m² = 194 × Cr (mg/dL)^−1.094 × age (years)^−0.287×0.739.

ACE: angiotensin converting enzyme; ARB: angiotensin II receptor blocker; BMI: body mass index; CCB: calcium channel blocker; DBP: diastolic blood pressure; eGFRcreat: glomerular filtration rate estimated from the serum creatinine concentration; SBP: systolic blood pressure; SD: standard deviation.

Table 2. Summary of overall safety data.

No. of patients, n (%)	Total (n = 341)
AEs	289 (84.8)
Related	131 (38.4)
Not related	158 (46.3)
Mild	215 (63.0)
Moderate	70 (20.5)
Severe	4 (1.2)
Leading to study drug discontinuation	32 (9.4)
Serious AEs	20 (5.9)
Related	0 (0.0)
Not related	20 (5.9)
Leading to study drug discontinuation	6 (1.8)
Deaths	0 (0.0)

AE: adverse event.

Table 3. All-cause AEs occurring in >2% of patients.

AEs by SOC and PT	Overall (n = 341) No. of patients (%)
Patients with any AE	289 (84.8)
Nasopharyngitis	106 (31.1)
Blood uric acid increased	86 (25.2)
Eczema	19 (5.6)
Hyperuricaemia	18 (5.3)
Back pain	18 (5.3)
Upper respiratory tract inflammation	18 (5.3)
Gastroenteritis	14 (4.1)
Pharyngitis	14 (4.1)
Diarrhoea	12 (3.5)
Bronchitis	12 (3.5)
Fall	11 (3.2)
Blood creatinine increased	10 (2.9)
Blood urea increased	10 (2.9)
Dizziness	10 (2.9)
Contusion	8 (2.3)
Blood triglycerides increased	8 (2.3)
Constipation	8 (2.3)
Malaise	7 (2.1)
Influenza	7 (2.1)
ALT increased	7 (2.1)
Cough	7 (2.1)

AE: adverse event; ALT: alanine aminotransferase; PT: preferred term; SOC: system organ class.

Figure 3. Time profile of mean office trough sitting SBP and DBP. p < .0001 versus week 0 at all post-baseline timepoints.

Table 4. Changes in office trough sitting SBP and DBP and morning home sitting SBP and DBP from baseline at each time point for the FAS.

Timepoint	N	Change in SBP from baseline (mmHg)			Change in DBP from baseline (mmHg)
		Mean (SD)	95% CI	p-value	Mean (SD)	95% CI	p-value
Office trough sitting BP
Baseline, Mean (SD)	341	143.7 (8.23)			86.2 (9.28)
Week 12 (LOCF)	339	–14.4 (12.72)	–15.72, –13.00	<.0001	–8.6 (8.97)	–9.57, –7.66	<.0001
Week 52 (LOCF)	339	–13.9 (12.14)	–15.21, –12.62	<.0001	–8.3 (9.26)	–9.28, –7.30	<.0001
Morning home sitting BP
Baseline, Mean (SD)	336	144.3 (13.60)			88.9 (9.54)
End of Week 12	331	–13.9 (10.67)	–15.08, –12.77	<.0001	–7.9 (6.59)	–8.59, –7.17	<.0001
End of treatment	318	–12.4 (11.75)	–13.69, –11.10	<.0001	–6.9 (7.23)	–7.74, –6.15	<.0001

BP: blood pressure; CI: confidence interval; DBP: diastolic blood pressure; FAS: full analysis set; LOCF: last observation carried forward; SBP: systolic blood pressure; SD: standard deviation.

Figure 4. Time profile of mean morning home sitting SBP and DBP. p < .0001 versus week 0 at all post-baseline timepoints.