Meta-analysis of three observational studies of amlodipine/valsartan in hypertensive patients with additional risk factors

Figures & data

Figure 1. Study schedules and number of participants in the three studies.

Table I. Demographic and baseline parameters.

	Number (%) or mean± SD	Median
Gender
Male	6544 (53.4)
Female	5429 (44.3)
Age (years)	63.4 ± 11.7	63.7
Age categorization
< 80 years	11,172 (91.1)
≥ 80 years	905 (7.4)
Height (cm)	170.8 ± 9.2	170.0
Weight (cm)	87.4 ± 16.3	86.0
BMI (kg/m^2)	29.9 ± 4.9	29.1
BMI categories
Missing	180 (1.5)
Normal body weight (< 25 kg/m^2)^a	1414 (11.5)
Pre-adiposity (≥ 25 and < 30 kg/m^2)	5555 (45.3)
Adiposity (≥ 30 kg/m^2)	5116 (41.7)
Systolic blood pressure at study start	162.3 ± 16.0	160.0
Systolic blood pressure (categories) at study start
Missing	14 (0.1)
< 140 mmHg	478 (3.9)
≥ 140 and < 160 mmHg	4170 (34.0)
≥ 160 and < 180 mmHg	5554 (45.3)
≥ 180 mmHg	2049 (16.7)
Diastolic blood pressure at study start	93.5 ± 9.8	95.0
Diastolic blood pressure (categories) at study start
Missing	11 (0.1)
< 80 mmHg	513 (4.2)
≥ 80 and < 90 mmHg	2297 (18.7)
≥ 90 and < 100 mmHg	5342 (43.6)
≥ 100 and < 110 mmHg	3269 (26.7)
≥ 110 mmHg	833 (6.8)
Essential hypertension
Yes	12,178 (99.3)
No	87 (0.7)
Duration of essential hypertension (years)	8.2 ± 6.7	7.1
Duration of essential hypertension (years) categories
Missing	605 (5.0)
< 1 year	1341 (11.0)
≥ 1 and < 5 years	3044 (25.0)
≥ 5 and < 10 years	3587 (29.5)
≥ 10 years	3601 (29.6)
Waist circumference (cm)	106.4 ± 13.7	105.0
Cardiovascular risk factors (most common)
Total	12,265 (100.0)
Dyslipidemia	8364 (68.2)
Positive family anamnesis	6809 (55.5)
Diabetes mellitus	6005 (49.0)
Smoker	3446 (28.1)
Coronary heart disease	2571 (21.0)
Left ventricular hypertrophy	2551 (20.8)
Congestive heart failure	1498 (12.2)
Microalbuminuria	1233 (10.1)
Antihypertensive pretreatment
Yes	10,482 (85.5)
No	1576 (12.8)
Prior medication for essential hypertension (most common)
ACE inhibitors, plain	3872 (36.9)
Angiotensin II antagonists and diuretics	1358 (13.0)
Angiotensin II antagonists, plain	1427 (13.6)
Beta blocking agents, selective	3241 (30.9)
Dihydropyridine derivatives	3154 (30.1)
Thiazides, plain	1060 (10.1)
Number of prior antihypertensive medications
Total	10,482 (100.0)
Prior medication not specified	273 (2.6)
One antihypertensive drug medication	4789 (45.7)
Two antihypertensive drugs	3336 (31.8)
Three antihypertensive drugs	1625 (15.5)
Four antihypertensive drugs	335 (3.2)
More than four antihypertensive drugs medications	124 (1.2)

ACE, angiotensin-converting enzyme. ^aIncludes 11 patients with a BMI of ≤ 18.5 kg/m².

Table II. Treatment with single-pill combination of amlodipine/valsartan – daily dose.

	Start of observation		6 weeks		16–24 weeks		Last visit
Daily dose of aml/val (mg)	n	%	n	%	n	%	n	%
Total	12,265	100.0	9537	100.0	12,097	100.0	12,212	100.0
Missing	17	0.1	219	2.3	171	1.4	189	1.5
5 mg/80 mg	1840	15.0	795	8.3	1118	9.2	1126	9.2
5 mg/160 mg	5988	48.8	4083	42.8	4959	41.0	5003	41.0
10 mg/160 mg	4420	36.0	4440	46.6	5849	48.4	5894	48.3

Figure 2. Time course of systolic and diastolic blood pressure – mean values.

Figure 3. Changes in blood pressure from baseline: (A) stratification by systolic blood pressure at baseline – mean values; (B) stratification by age – mean values; (C) stratification by body mass index (BMI) – mean values; (D) stratification by diabetes mellitus status.

Figure 3. (Continued).

Table III. Normalization of blood pressure and response at last control.

	Normalization		Response I^a		Response II^b
	n	(%)	n	(%)	n	(%)
Total	4740	38.8	9273	75.9	6390	52.3
Aml/val – dose at last control
5 mg/80 mg	556	49.4	895	79.5	714	63.4
5 mg/160 mg	2113	42.2	3844	76.8	2826	56.5
10 mg/160 mg	2024	34.3	4424	75.1	2789	47.3
Body mass index
< 25 kg/m^2	552	44.5	971	78.3	709	57.2
≥ 25 kg/m^2 to < 30 kg/m^2	2135	41.2	3981	76.7	2877	55.5
≥ 30 kg/m^2	1812	36.7	3716	75.2	2406	48.7
Diabetes mellitus
Yes	1018	17.0	4046	67.6	2999	50.1
No	3722	59.8	5227	84.0	3391	54.5
Prior anti-hypertensive treatment
Yes	3973	38.0	7808	74.8	5428	52.0
No	693	44.3	1318	84.2	859	54.9
Systolic blood pressure at start of observation
< 140 mmHg	237	53.3	248	55.7	219	49.2
≥ 140 to < 160 mmHg	1917	48.7	2589	65.8	2340	59.4
≥ 160 to < 180 mmHg	1883	36.1	4248	81.4	2728	52.3
> 180 mmHg	503	26.4	1673	87.8	774	40.6
Diastolic blood pressure at start of observation
< 90 mmHg	1239	44.4	1608	57.6	1447	51.8
≥ 90 mmHg	3499	37.2	7663	81.4	4942	52.5
Age
< 80 years	4375	39.3	8455	76.0	5828	52.4
≥ 80 years	300	33.4	671	74.7	466	51.9

For definition of normalization, see methods section. ^aResponse I = therapeutic response (in EXPAND-M and EXPAND-O therapeutic response was defined as systolic blood pressure < 140 mmHg or at least 20 mmHg decrease vs baseline and diastolic blood pressure < 90 mmHg or at least 10 mmHg decrease vs baseline, while in EXPAND-D therapeutic response was defined as systolic blood pressure < 130 mmHg or at least 20 mmHg decrease vs baseline and diastolic blood pressure < 80 mmHg or at least 10 mmHg decrease vs baseline). ^bResponse II = reached target blood pressure defined by treating physician.

Table IV. Most frequently reported adverse events (≥ 0.05% of patients and more than 1 patient) – by age group.

	Total, n = 12,265		< 80 years, n = 11,172		≥ 80 years, n = 905
	n	%	n	%	n	%
Edema peripheral	116	0.95	104	0.93	11	1.22
Edema	22	0.18	19	0.17	3	0.33
Dizziness	13	0.11	13	0.12	0	0.00
Headache	11	0.09	11	0.10	0	0.00
Flushing	10	0.08	9	0.08	1	0.11
Pruritus	8	0.07	8	0.07	0	0.00
Cough	7	0.06	7	0.06	0	0.00