Olmesartan vs ramipril in the treatment of hypertension and associated clinical conditions in the elderly: a reanalysis of two large double-blind, randomized studies at the light of the most recent blood pressure targets recommended by guidelines

Figures & data

Table 1 Demographic and clinical characteristics of the 1,426 patients of the intention-to-treat population of the two studies pooled together

	Olmesartan 10–40 mg (n=712)	Ramipril 2.5–10 mg (n=714)	P-value
Age (years)	72.0±5.2	72.1±5.0	0.689
65–69	298 (41.9)	299 (41.9)	0.954
70–79	351 (49.3)	355 (49.7)
>80	63 (8.8)	60 (8.4)
Sex
Male	355 (49.9)	362 (50.7)	0.751
Female	357 (50.1)	352 (49.3)
Height (cm)	165.8±8.7	165.5±8.7	0.623
Weight (kg)	73.8±11.8	74.1±11.5	0.613
BMI (kg/m^2)	26.8±3.5	27.0±3.2	0.339
Waist circumference (cm)a	96.1±11.6	96.3±11.5	0.790
Significant medical history	586 (82.3)	588 (82.4)	0.980
Concomitant treatments	480 (67.4)	492 (68.9)	0.545
Hypertension medication in the previous 3 months	538 (75.6)	537 (75.2)	0.877
Number of previous antihypertensive drugs
None	174 (24.4)	179 (25.1)	0.682
1	348 (48.9)	333 (46.6)
2 or more	190 (26.7)	202 (28.3)
Type of previous antihypertensive drugsb
ACE inhibitors	208 (38.7)	214 (39.9)	0.672
Angiotensin II receptor blockers	215 (40.0)	210 (39.2)	0.793
Calcium channel blockers	170 (31.6)	127 (23.7)	0.004
Diuretics	54 (10.0)	73 (13.6)	0.069
Beta-blockers	85 (15.8)	100 (18.7)	0.215
Alpha-blockers	36 (6.7)	43 (8.0)	0.403
Others	10 (1.9)	12 (2.2)	0.660
Metabolic syndrome	372 (52.2)	363 (50.8)	0.595
Central or peripheral obesity	557 (78.2)	573 (80.3)	0.347
Dyslipidemia	601 (84.4)	610 (85.4)	0.589
Diabetes	138 (19.4)	153 (21.4)	0.338
CKD stages
Normal or increased eGFR (≥90 mL/min/1.73 m^2)	89 (12.5)	92 (12.9)	0.973
Slightly reduced eGFR (60–90 mL/min/1.73 m^2)	421 (59.1)	419 (58.7)
Moderately or severely reduced eGFR (<60 mL/min/1.73 m^2)	202 (28.4)	203 (28.4)
Cardiovascular risk level
Low-moderate (≤5%)	80 (11.2)	79 (11.1)	0.918
High-very high (>5%)	632 (88.8)	635 (88.9)
Office SBP (mmHg)	157.1±10.0	156.6±10.0	0.407
Office DBP (mmHg)	91.8±6.7	91.3±6.7	0.103
Type of hypertension
Diastolic ± systolic	550 (77.2)	527 (73.8)	0.131
Isolated systolic	162 (22.8)	187 (26.2)

Notes: Data are shown as means (± SD) or as absolute (n) and relative (%) frequencies. P-values for between-treatment difference are also reported.

a Available for 699 patients randomized to olmesartan and for 703 patients randomized to ramipril.

b Percentages refer to treated patients (n=1,074).

Abbreviations: BMI, body mass index; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; SBP, systolic blood pressure; DBP, diastolic blood pressure; SD, standard deviation; ACE, angiotensin-converting enzyme.

Figure 1 Percentage of normalized patients according to different thresholds.

Notes: (A) Original study thresholds, <140/90 mmHg in nondiabetics and <130/80 mmHg in diabetics. (B) <140/90 mmHg for all patients. (C) <150/90 mmHg for all patients after 2, 6, and 12 weeks of treatment with olmesartan 10–40 mg (white bars) or ramipril 2.5–10 mg (black bars). P-values for between-treatment difference are also reported.

Table 2 Blood pressure response to olmesartan monotherapy in elderly patients with systolic and/or diastolic hypertension or isolated systolic hypertension in different open-label or double-blind randomized studies

Author, year (ref)	Country	Number of patients	Study design	Age (years)	BP at entry	Washout (weeks)	Treatment duration	Type of treatment	Blood pressure normalization
Kereiakes et al 2009^Citation21	USA	176	Open-label, randomized, blinded endpoint	≥65	DBP ≥90 mmHg and/or SBP ≥140 mmHg	2 (placebo)	12 weeks	Olmesartan 20 or 40 mg	BP <140/90 mmHg: 52.3%
Saito et al 2008^Citation22	Japan	481	Open-label, randomized, prospective	≥65	DBP ≥90 mmHg and/or SBP ≥140 mmHg	None	24 weeks	Olmesartan 5, 10, 20 or 40 mg (+ other antihypertensive drugs)	BP <140/90 mmHg: 50.0%
Heagerty and Mallion 2009^Citation23	Europe	251	Double-blind, randomized	≥65	DBP 100–114 mmHg SBP 151–200 mmHg	2 (placebo)	52 weeks	Olmesartan 20 or 40 mg	DBP ≤90 mmHg: 74.5%
Ogawa et al 2012^Citation24	Japan	578	Open-label, randomized, prospective, blinded endpoint	65–84	DBP ≥90 mmHg and/or SBP ≥140 mmHg	2–4 (olmesartan 20 mg)	3 years	Olmesartan 40 mg	BP <140/90 mmHg: 62.1%
Mallion et al 2007^Citation25	Europe	256	Double-blind, randomized	≥65	DBP <90 mmHg SBP 161–200 mmHg	2 (placebo)	24 weeks	Olmesartan 20 or 40 mg	SBP ≤135 mmHg: 67.6%

Abbreviations: DBP, diastolic blood pressure; SBP, systolic blood pressure; BP, blood pressure.

Table 3 Percentage of normalized and normalized or responder patients after 12 weeks of treatment with olmesartan medoxomil 10–40 mg (n=712) or ramipril 2.5–10 mg (n=714), according to sex, age and 10-year cardiovascular risk category (low-moderate: <5% and high-very high: ≥5%)

	Normalized patients (<140/90 mmHg)			Normalized patients (<150/90 mmHg)
	Olmesartan 10–40 mg	Ramipril 2.5–10 mg	P-value	Olmesartan 10–40 mg	Ramipril 2.5–10 mg	P-value
Sex
Male (n=717)	199 (56.1)	174 (48.1)	0.032	253 (71.3)	222 (61.3)	0.005
Female (n=709)	194 (54.3)	173 (49.1)	0.166	246 (68.9)	229 (65.1)	0.276
Age
65–69 years (n=597)	183 (61.4)	147 (49.2)	0.003	221 (74.2)	184 (61.5)	0.001
70–79 years (n=706)	174 (49.6)	172 (48.5)	0.766	232 (66.1)	226 (63.7)	0.498
>80 years (n=123)	36 (57.1)	28 (46.7)	0.245	46 (73.0)	41 (68.3)	0.568
10-year Cardiovascular risk
Low-moderate (n=159)	54 (67.5)	46 (60.8)	0.376	64 (80.0)	57 (72.2)	0.246
High-very high (n=1,267)	339 (53.6)	299 (47.1)	0.020	435 (68.8)	394 (62.0)	0.011

Figure 2 Percentage of normalized patients.

Notes: (A) <140/90 mmHg. (B) <150/90 mmHg after 12 weeks of treatment with olmesartan 10–40 mg (white bars) or ramipril 2.5–10 mg (black bars) according to the presence of specific metabolic abnormalities. P-values for between-treatment difference are also reported.

Figure 3 Percentage of normalized patients.

Notes: (A) <140/90 mmHg. (B) <150/90 mmHg after 12 weeks of treatment with olmesartan 10–40 mg (open square) or ramipril 2.5–10 mg (full square) according to estimated glomerular filtration rate (eGFR). P-values for between-treatment difference are also reported.

Figure 4 Percentage of normalized patients.

Notes: (A) <140/90 mmHg. (B) <150/90 mmHg after 12 weeks of treatment with olmesartan 10–40 mg (white bars) or ramipril 2.5–10 mg (black bars) according to the number and type of previous antihypertensive drugs. P-values for between-treatment difference are also reported.
Abbreviations: ACE, angiotensin-converting enzyme; ARB, angiotensin-receptor blocker.

KereiakesDJNeutelJStoakesKAThe effects of an olmesartan medoxomil-based treatment algorithm on 24-hour blood pressure levels in elderly patients aged 65 and olderJ Clin Hypertens (Greenwich)200911841142119695028

 PubMed Web of Science ®Google Scholar

SaitoIKushiroTHirataKThe use of olmesartan medoxomil as monotherapy or in combination with other antihypertensive agents in elderly hypertensive patients in JapanJ Clin Hypertens (Greenwich)200810427227918401224

 PubMed Web of Science ®Google Scholar

HeagertyAMMallionJMOlmesartan medoxomil in elderly patients with essential or isolated systolic hypertension: efficacy and safety data from clinical trialsDrugs Aging2009261617619102515

 PubMed Web of Science ®Google Scholar

OgawaHKim-MitsuyamaSMatsuiKAngiotensin II receptor blocker-based therapy in Japanese elderly, high-risk, hypertensive patientsAm J Med20121251098199022503610

 PubMed Web of Science ®Google Scholar

MallionJMHeagertyALaeisPSystolic blood pressure reduction with olmesartan medoxomil versus nitrendipine in elderly patients with isolated systolic hypertensionJ Hypertens200725102168217717885562

 PubMed Web of Science ®Google Scholar