Aliskiren/amlodipine as a single-pill combination in hypertensive patients: subgroup analysis of elderly patients, with metabolic risk factors or high body mass index

Figures & data

Table 1.  Overview of studies with aliskiren in obese, elderly, or metabolic impaired patients.

Author and references	Design	Subgroup n	Duration (weeks)	Aliskiren schedule (mg/day)	Control drug schedule (mg/day)	ΔSBP/DBP vs. baseline in the aliskiren group (mmHg)	ΔSBP/DBP vs. baseline in the control group (mmHg)
Obese (BMI ≥30)
Schmieder37	r, pc, db, mc	396	12	150 → 300	HCT 12.5 → 25	16.7/12.3	12.2/9.1
			52	+AMLO 5 → 10	+AMLO 5 → 10	19.9/15.5	17.6/13.3
Jordan36	r, pc, db, mc	489	8	HCT 25 + 150 → 300	HCT 25 + irbesartan 150 → 300	15.8/11.9	15.4/11.3
			8		HCT 25 + AMLO 5 → 10		13.6/10.3
			8		HCT 25		8.6/7.9
Whaley-Conell38	r, c, db, mc	386	8	150 → 300 + HCT 12.5 → 25	Ramipril 5 → 10	28.1/10.1	16.6/3.6
Braun-Dullaeus39	r, c, db, mc	482	8	150 → 300 + AMLO 5 → 10	AMLO 5 → 10	35.9/15.1	30.0/10.9
Weir61	Pooled meta-analysis	905	8–12	300	Placebo	13.9/11.1	4.9/6.1
Elderly (aged 65+ years)
Verdecchia54	r, c, db, mc	355	8	75	Lisinopril 10	8.4/4.5	10.2/6.3
				150		7.1/3.6
				300		8.7/3.9
Duprez55	r, c, db, mc	901	12	150 → 300	Ramipril 5 → 10	14.0/5.1	11.6/3.6
			22	+HCT 12.5 → 25	+HCT 12.5 → 25	19.6/8.2	17.3/7.3
			36	+HCT 12.5 → 25 + AMLO 5 → 10	+HCT 12.5 → 25 + AMLO 5 → 10	20.0/8.2	18.1/7.0
Yarows61	r, pc, db, mc	1797	8	150 → 300	Placebo	14.5/8.6	5.1/5.3
				+VAL 160 → 320	VAL 160 → 320	19.0/12.6	12.2/11.0
Gradman62	Pooled	704	8–12	150	Placebo	13.4/11.7	4.4/8.1
				300		14.9/12.3
Littlejohn63	o, mc	101	54	150 → 300 + AMLO 5 → 10 (+HCT 12.5 → 25)		30.4/17.6
Basile64	r, c, db, mc	54	8	150 → 300 + HCT 12.5 → 25		34.2/24.0
Schmieder56	o, prospective	7399	52	150 → 300 ± other antihypertensive drug	ACEi/ARBs No ACEI/ARBs	19.6/7.6	15.5/6.3 16.3/6.6
					No ACEi/ARB		9.6/6.7
Villa53	r, pc, db	754	8	75	Placebo	13/5	8/4
				150		15/6
				300		14/7
Diabetes mellitus
Uresin47	r, c, mc	560	8	150 → 300	Ramipril 5 → 10	14.7/11.3	12.0/10.7
Taylor49	Meta-analysis	1417	8–12	150	Placebo	13.2/10.4	6.9/7.8
				300		14.8/12.2
Townsend48	r, c, db, mc	860	8	150 → 300 (+HCT 12.5 → 25)	AMLO 5 → 10	28.8/9.9	26.2/9.0
Verpooten51	o, prospective	759	26	150 → 300		25.1/11.3
Sowers65	Meta-analysis	1035	8–12	150	Placebo	12.7/7.8	6.8/5.7
				300		15.2/11.6
Zeymer50	o, prospective	4242	52	150 → 300	ACEi/ARB	18.2/7.7	14.7/6.5
					Non ACEi/ARB		14.2/6.3
Braun-Dulleaus66	r, db, c, mc	219	8	150 → 300 + Am 5 → 10	AMLO 5 → 10	34.4/15.2	30.5/12.3
Metabolic syndrome
Weinberger43	r, c, db, mc	197	8	150 → 300 + AMLO 5 → 10	AMLO 5 → 10	36.4/15.0	28.5/10.5
Krone41	r, c, db	141	12	300	Irbesartan 300	13.8/7.1	5.8/2.8
White67	Meta-analysis	2903	8–12	150	Placebo	13.3/10.4	5.1/5.8
				300		14.8/11.3
Lacourciere68	r, db, mc, c	613	8	ALIS 300 + AMLO 10 + HCT 25	ALIS 300 + AMLO 10	36.2/20.0	28.9/16.9
					ALIS 300 + HCT 25		26.6/13.9
					AMLO 10 + HCT 25		29.7/16.5
Ferdinand44	r, db, mc, c	284	8	ALIS 300 + AMLO 10	ALIS 300 + AMLO 10 + HCT 25	28.2/11.9	34.9/14.9
Gradman42	Pooled	166 238	8 -- 12	150 300	Placebo	15.0/11.4 15.1/11.7	5.0/5.9

Δ, difference; c, (active) controlled; db, double blind; HCT, hydrochlorothiazide; mc, multicenter; r, randomized; o, open; pc, placebo controlled; ACEI, angiotensin converting enzyme inhibitor; ALIS, aliskiren; AMLO, amlodipine; ARB, angiotensin receptor blocker; HCT, hydrochlorothiazide; VAL, valsartan.

→ indicates titration step (e.g. 150 → 300: from 150 mg/day to 300 mg/day).

Figure 1.  Study design. *Visit 2 was performed only in patients with previous antihypertensive therapy. **Patients with an office mean sitting DBP<90 mmHg at an unscheduled visit after visit 4 or at visit 5 were discontinued from the study. Dotted box highlights study phase from which data were analyzed for this paper.

Table 2.  Baseline characteristics in all 3 phases, including subgroups in phase 2.

Parameter	Phase 1	Phase 2								Phase 3
	Safety population^1	All subgroups								Safety population
		ITT population	BMI 25–29.9	BMI ≥30	Met risk	Met risk no DM	Met risk DM yes	Age <65 years	Age ≥65 years
	OLME 40/ AMLO 10	ALIS 300/ AMLO 10								ALIS 300/AMLO 10/HCT 12.5
Number of patients	342	187	74	89	132	91	41	118	69	65
Age (years) mean (±SD)	60.4 (10.9)	60.5 (10.7)	60.9 (10.9)	59.4 (10.9)	60.7 (10.3)	59.2 (10.6)	64.0 (8.6)	54.3 (8.1)	71.1 (4.6)	60.8 (10.8)
Gender – n (%)
Male	182 (53.2)	109 (58.3)	46 (62.2)	54 (60.7)	79 (59.8)	55 (60.4)	24 (58.5)	69 (58.5)	40 (58.0)	46 (70.8)
Female	160 (46.8)	78 (41.7)	28 (37.8)	35 (39.3)	53 (40.2)	36 (39.6)	17 (41.5)	49 (41.5)	29 (42.0)	19 (29.2)
Race – n (%)
Caucasian	340 (99.4)	185 (98.9)	73 (98.6)	88 (98.9)	132 (100)	91 (100)	41 (100)	116 (98.3)	69 (100.0)	64 (98.5)
Black/other	2 (0.6)	2 (1.1)	1 (1.4)	1 (1.1)	0 (0.0)	0 (0.0)	0 (0.0)	2 (1.7)	0 (0.0)	1 (1.5)
Weight (kg) mean (±SD)	88.5 (19.3)	90.6 (20.1)	82.5 (10.4)	103.4 (19.7)	90.4 (19.7)	87.8 (16.4)	96.3 (25.0)	94.4 (22.6)	84.0 (12.7)	91.1 (19.0)
SBP (mmHg) mean (±SD)	166.6 (6.2)	167.9 (5.3)	167.9 (5.2)	167.1 (5.3)	168.3 (5.4)	168.0 (5.1)	168.9 (5.8)	166.8 (4.9)	169.7 (5.5)	168.3 (5.2)
DBP (mmHg) mean (±SD)	103.1 (3.0)	103.6 (2.6)	103.5 (2.7)	103.4 (2.5)	103.7 (2.6)	103.8 (2.7)	103.6 (2.5)	103.6 (2.4)	103.6 (2.9)	103.3 (2.3)

BMI, body mass index; DBP, diastolic blood pressure; DM, diabetes mellitus; ITT, intent-to-treat; HCT, hydrochlorothiazide.

Met risk, at least one metabolic risk factor present; SBP, systolic blood pressure.

Values are means (SD, standard deviation), or percentages (n (%))

Figure 2.  Blood pressure reduction on aliskiren/amlodipine in the total cohort (ITT population) and in subgroups in phase 2 (week 8 compared with week 4).

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