Aim
: The objective of this study was to compare the antihypertensive efficacy and safety of the angiotensin II antagonist olmesartan medoxomil and the ACE inhibitor ramipril in elderly patients with ...mild to moderate essential hypertension, grouped according to renal function.
Methods
: We performed a
post hoc
analysis of pooled data from two randomized, double-blind, parallel-group, multicentre studies. After a 2-week placebo wash-out period, 1453 mild to moderate hypertensive subjects were randomized to a 12-week treatment with olmesartan medoxomil 10 mg/day or ramipril 2.5 mg/day. After 2 and 6 weeks, doses were increased up to a maximum of 40 mg/day (olmesartan medoxomil) and 10 mg/day (ramipril) in non-normalized subjects (office systolic blood pressure SBP ≥ 140 mmHg or diastolic blood pressure DBP ≥90 mmHg in non-diabetic subjects and office SBP ≥ 130 mmHg or DBP ≥80 mm Hg in diabetic patients). Office blood pressure (BP) was measured at 0, 2, 6 and 12 weeks, 24-hour ambulatory BP at 0 and 12 weeks. 284 patients treated with olmesartan medoxomil 40 mg/day at the end of the double-blind period entered a 36-week, open-label follow-up. Renal function (Cockroft-Gault equation) was evaluated as normal or increased estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m
2
, mild eGFR reduction (60–90 mL/min/1.73 m
2
) and moderate or severe eGFR reduction (<60 mL/min/1.73 m
2
).
Results
: 181 (12.7%) subjects had normal or increased eGFR, 840 (58.9%) mild eGFR reduction, and 405 (28.4%) moderate or severe eGFR reduction. Baseline-adjusted office BP reductions were superior with olmesartan medoxomil than with ramipril in normal or increased (olmesartan medoxomil — ramipril difference SBP: 5.0 mmHg 95% CI 9.1, 0.9, p = 0.018; DBP: 2.7 mmHg 4.8, 0.6, p = 0.011) and mildly reduced eGFR patients (SBP: 1.6 mmHg 3.5, 0.2, p = 0.080; DBP: 1.2 mmHg 2.3, 0.2, p = 0.022). In the group with moderately or severely reduced eGFR the two treatments were comparable (SBP: 1.9 mmHg 4.6, 0.9, p = 0.185; DBP: 0.8 mmHg 2.3, +0.7; p = 0.296). At 12 weeks, the rate of normalized patients was 46.1 % with olmesartan medoxomil versus 23.9% with ramipril (p = 0.002) in the normal, and 49.9% versus 42.7% (p = 0.037) in the mild eGFR reduction group. No significant differences in normalization rate were observed in the moderately or severely reduced eGFR group (olmesartan medoxomil 49.5% vs ramipril 46.3%, p = 0.519). eGFR did not show any significant change during treatment.
Conclusions
: Olmesartan medoxomil provides a more effective BP control, similar if not superior to that of ramipril, independently from the patient’s renal function status.
Circadian blood pressure (BP) measurements provide more information on hypertensive complications than office BP measurements. The purpose of this study was to analyze the efficacy of the first-line ...combination of perindopril 2 mg plus indapamide 0.625 mg versus atenolol 50 mg on BP parameters and variability over 24 h in patients with hypertension.
A double-blind, randomized, controlled, 12-month study comparing perindopril/indapamide and atenolol was performed in 201 patients (age 55.0 years) with uncomplicated sustained essential hypertension. Ambulatory BP measurements (ABPM) were done every 15 min over 24 h.
After 1 year of treatment, the decrease in systolic BP was significantly greater for perindopril/indapamide than for atenolol during the entire 24-h period (-13.8
v −9.2 mm Hg), the daytime and the nighttime periods (
P < .01). Diastolic blood pressure (DBP) variations were comparable for the two groups (−7.2
v −8.3 mm Hg, NS). Pulse pressure (PP) reduction was also significantly greater for perindopril/indapamide than for atenolol (for the whole 24 h, −6.6
v −0.9 mm Hg,
P < .001). The through to peak (T/P) BP ratio and the smoothness index were comparable in the two groups for DBP. For systolic blood pressure (SBP), higher values of the T/P ratio (0.80
v 0.59) and the smoothness index (1.45
v 0.98;
P < .02) were achieved for the perindopril/indapamide combination than for atenolol.
The perindopril/indapamide first-line combination decreased SBP and PP more effectively than atenolol. Moreover, the BP control effect was smooth and consistent throughout the 24-h dosing interval and BP reduction variability was lower than the one induced by atenolol.
Abstract
Objective. To compare the efficacy and safety of olmesartan medoxomil (O) and ramipril (R) in elderly patients with essential arterial hypertension. Methods. After a 2-week placebo washout, ...351 elderly hypertensive patients aged 65-89 years (office sitting diastolic blood pressure, DBP, 90-109 mmHg and office sitting systolic blood pressure, SBP, 140-179 mmHg) were randomized double-blind to 12-week treatment with O 10 mg or R 2.5 mg once daily. After the first 2 and 6 weeks, doses could be doubled in non-normalized (blood pressure <140/90 mmHg for non-diabetic and <130/80 mmHg for diabetic) subjects, up to 40 mg for O and 10 mg for R. Office blood pressures were assessed at randomization, after 2, 6 and 12 weeks of treatment; 24-h ambulatory blood pressure (ABP) was recorded at randomization and after 12 weeks. Results. At week 12, in the intention-to-treat population (170 patients O and 175 R) the rate of normalized subjects was significantly larger in the O group (38.8% vs 26.3% R; p = 0.013). Baseline-adjusted mean sitting office blood pressure reduction at final visit was not significantly greater under O SBP: 16.6 (95% confidence interval 14.0/19.2) mmHg vs 13.0 (10.4/15.6) mmHg R, p = 0.206; DBP: 11.8 (10.3/13.3) mmHg vs 10.5 (9.0/12.0) mmHg, p = 0.351. In the subgroup of patients with valid ABP recordings (38 O and 47 R), the reduction in 24-h average blood pressure was significantly (p < 0.01) larger with O SBP: 8.9 (9.8/8.1) and DBP: 5.7 (6.3/5.1) mmHg than with R 6.7 (7.9/5.6) and 4.4 (5.1/3.7) mmHg. The superiority of O was particularly evident in the last 4 h from the dosing interval. The proportion of patients with drug-related adverse events was comparable in the two groups (4.0% O vs 4.5% R), as well as the number of patients discontinuing study drug because of a side-effect (8 O vs 7 R). Conclusions. In elderly patients with essential arterial hypertension, O provides an effective, prolonged and well tolerated blood pressure control, with significantly better blood pressure normalization than R and represents a useful option among first-line drug treatments of hypertension in this age group.
The baroreflex plays an essential role in regulating the cardiovascular system. However, very few studies have focused on the links between genetic polymorphisms and baroreflex sensitivity (BRS).
A ...total of 146 hypertensive individuals who had never been treated, and 105 healthy individuals (controls) were included in the study. The genotypes of 17 polymorphisms of 11 genes involved in the regulation of the cardiovascular system were studied. BRS was measured using a sequence method: BRS was evaluated as the slope of spontaneous increases systolic blood pressure (SBP)+/reflex response (RR)+ or decreases (SBP-/RR-) in SBP and pulse interval by recording blood pressure (BP) continuously for 20 min.
Following univariate analysis, the genetic polymorphism of endothelin receptor A EDNRA/C+1222T was found to be significantly correlated with the BRS (SBP-/RR-) level in both populations. In normotensive subjects, mean BRS values (SBP-/RR-) were 11.93 +/- 3.69 ms/mmHg in EDNRA CC homozygotes, 9.94 +/- 2.97 ms/mmHg in CT heterozygotes and 9.51 +/- 3.16 ms/mmHg in TT homozygotes (P = 0.01). In hypertensive subjects, mean BRS values (SBP-/RR-) were 9.26 +/- 3.59 ms/mmHg in EDNRA CC homozygotes, 9.03 +/- 4.14 ms/mmHg in CT heterozygotes and 6.60 +/- 2.42 ms/mmHg in TT homozygotes (P = 0.01). After adjustment for age, sex, SBP and diastolic blood pressure and body mass index, the EDNRA/C+1222T polymorphism remained significantly correlated with BRS in both normotensive (P = 0.01) and hypertensive (P = 0.01) subjects.
These results suggest that the endothelin system may be involved in the regulation of BRS in humans. In particular, the T allele of the EDNRA/C+1222T polymorphism is associated with a reduction in BRS in both healthy and hypertensive subjects.
The objective of this study was to describe and analyse the nycthemeral variations in blood pressure (BP) by ambulatory BP monitoring (ABPM) over 24 h in patients with heart failure (HF).
The study ...population included 50 stable HF patients hospitalized in a cardiology department for acute pulmonary oedema. Parameters studied were: New York Heart Association class, clinical resting BP and heart rate in sitting and then standing positions, ABPM parameters, distance covered during a 6-min walking test, echographic left ventricular ejection fraction (LVEF), natremia, kaliemia, creatininemia, plasma haemoglobin and N-terminal fragment of brain-type natriuretic peptide levels.
Clinical hypertension was noted in 20% of patients (10/50) and orthostatic hypotension in 16% (8/50). Nine of 50 patients (18%) were hypertensive during the day and 21 (42%) at night. Thirty-nine of the 50 patients (78%) are nondippers. Nondipper patients are more prevalent when the HF has been present for more than 24 months (95 vs. 67%, P=0.04). This prevalence does not differ depending on New York Heart Association class or LVEF. Furthermore, there exists: (i) a significant positive relationship (R=0.46, P=0.02) between the diastolic BP (DBP) over 24 h and the distance covered during the walking test; (ii) a significant negative relationship between the day-night differences (in mmHg) of the systolic BP (SBP) (R=-0.46, P=0.01) and DBP (R=-0.33, P=0.03) and the duration of HF, between the day-night difference of the DBP and the LVEF (R=-0.34, P=0.02) and (iii) between the day-night differences of the SBP (R=-0.48, P=0.001) and the DBP (R=-0.32, P=0.03) and natremia. The day-night difference of the SBP has a positive correlation with plasma haemoglobin level (R=0.32, P=0.03).
This study confirms the feasibility of carrying out ABPM with an adapted device in HF patients with atrial fibrillation. ABPM allows diagnosis to be more precise than the clinical measuring of BP abnormalities, which have a pejorative prognosis (e.g. hypertension, hypotension, nondipper status).
We evaluated the clinical validity of the AGILIS ambulatory blood pressure monitor according to the European Society of Hypertension International Protocol.
The blood pressure (BP) was measured at ...the same arm by two certified observers using two mercury columns and a double stethoscope, then by the volunteer with the automatic device, these measurements were done seven times sequentially using 33 volunteers. For the randomization of the patient, one ABPM measure was compared to the mean of three manual measures. Then, we had three ABPM measures and four manual measures. Each ABPM measure, being compared to two manual measures. Blood pressure readings and recordings were blinded. Position of the subjects was standardized.
Phase 1: To pass phase 1, the device had to have at least 25 of the 45 measurements within 5 mmHg, 35 within 10 mmHg or 40 within 15 mmHg of the comparative observer measurements. The AGILIS monitor had 35 measurements lying within 5 mmHg, 42 within 10 mmHg and 45 within 15 mmHg for systolic BP (SBP), 35 within 5 mmHg, 44 within 10 mmHg and 45 within 15 mmHg for diastolic BP (DBP). It passed the criteria for SBP and DBP. Phase 2: To pass phase 2.1, a device must have at least 60 of 99 measurements within 5 mmHg, 75 within 10 mmHg and 90 within 15 mmHg of the comparative observer measurements, and in addition must also have either 65 within 5 mmHg and 80 within 10 mmHg, or 65 within 5 mmHg and 95 within 15 mmHg, or 80 within 10 mmHg and 95 within 15 mmHg. The AGILIS monitor had 78 measurements within 5 mmHg, 91 within 10 mmHg and 96 within 15 mmHg for SBP; and 70 measurements within 5 mmHg, 92 within 10 mmHg and 96 within 15 mmHg for DBP. It passed the criteria for SBP and DBP. For phase 2.2 using the AGILIS monitor, 27 subjects had at least two of the differences within 5 mmHg and none had any differences within 5 mmHg for SBP; 27 subjects had at least two of the differences within 5 mmHg and three subjects had no differences within 5 mmHg for DBP. The results are in concordance with the requested criteria for phase 2.2.
Thus the AGILIS device fulfils the validation criteria of the international protocol.
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