e276 Journal of Hypertension

Vol 28, e-Supplement A, June 2010

PP.16.86

TREATMENT OF NON-DIPPER ESSENTIAL HYPERTENSION BY BEDTIME ADMINISTRATION OF ANGIOTENSIN RECEPTOR BLOCKERS

Conclusions: AZL-M demonstrated more effective BP lowering than VAL at the maximal dose of VAL approved for the treatment of hypertension, and a safety and tolerability prole similar to that of VAL.

R. Hermida, D.E. Ayala, M.J. Fontao, A. Mojon, J.R. Fernandez. University of Vigo, Vigo, Spain Objectives: Non-dipping has been related to increased end-organ injury and cardiovascular risk. Accordingly, there is growing interest in how to tailor the treatment of non-dipper hypertensives. Clinical studies have documented that dosing of angiotensin-receptor blockers (ARB) at bedtime as opposed to upon wakening increases the sleep-time relative blood pressure (BP) decline and their efcacy in lowering asleep BP. Accordingly, we investigated the antihypertensive efcacy of ARB monotherapy when dosed either on awakening or at bedtime in non-dipper hypertensive subjects. Methods: We studied 453 untreated subjects with grade 12 essential hypertension (210 men and 243 women), 53.1 14.2 years of age, all with a non-dipper BP prole at inclusion. Subjects were randomly assigned to receive ARB monotherapy (valsartan, 160 mg/day; olmesartan, 40 mg/day; or telmisartan, 80 mg/day) either on awakening or before bedtime. BP was measured at 20-min intervals from 07:00 to 23:00 h and at 30-min intervals at night for 48 h before and after 12 weeks of treatment. Results: The reduction in awake BP was similar for both treatment-times (11.0/8.0 mmHg reduction of systolic/diastolic awake BP after ARB on awakening; 10.2/7.3 mmHg after ARB at bedtime; P > 0.293 between treatment-groups). Treatment at bedtime, however, was signicantly more efcient in reducing asleep BP (18.5/11.9 mmHg reduction compared to 12.8/8.8 mmHg after morning treatment; P < 0.001). The sleep-time relative BP decline was increased by 6.9 (P < 0.001) towards a more dipping pattern after bedtime dosing, which resulted in 72% of the patients reverted to dippers. This increase in sleep-time relative BP decline was similar for all three ARB tested (P > 0.503). Conclusions: Bedtime administration of ARB in non-dipper hypertensives provides a higher efcacy as compared to morning treatment in reducing the asleep BP mean, and improves the sleep-time relative BP decline towards a more dipper prole. This might be clinically relevant, as nighttime BP is a better prognostic marker of cardiovascular mortality than awake BP. These effects were comparable for all ARB tested here, despite marked differences in plasma-half-life. PP.16.87 ABSTRACT WITHDRAWN

PP.16.89

SUPERIORITY OF LOW DOSE DIURETICS COMBINATION OVER RENIN-ANGIOTENSIN BLOCKERS COMBINATION IN RESISTANT HYPERTENSION

M. Frank1, G. Bobrie2, M. Azizi1,3, S. Peyrard4, P. Boutouyrie3,5,6, G. Chatellier3,4, S. Laurent3,5,6, J. Menard1, P.F. Plouin2,3. 1APHP, Georges Pompidou European Hospital, Clinical Investigation Center, Paris, France, 2 APHP, Georges Pompidou European Hospital, Hypertension Unit, Paris, France, 3 Universite Paris Descartes, Paris, France, 4CIC-EC4 INSERM, Georges Pompidou European Hospital, Paris, France, 5APHP, Georges Pompidou European Hospital, Department of Pharmacology, Paris, France, 6INSERM U 970, Paris, France In case of resistant essential hypertension (RH), guidelines recommend to increase the treatment, especially diuretics, without precision of use. Objective: To compare in RH patients (pts), over a three-month period, the efcacy and the safety of 2 stepped care strategies chosen to limit counter regulations: either to increase sodium depletion by combining low doses of diuretics acting at different sites of the renal tubule (D group) or to combine renin-angiotensin system blockers (RASB, R group). Methods: In a PROBE study, after a standardized 4-week (W) 3 drugregimen (irbesartan 300 mg/d, hydrochlorothiazide 12.5 mg/d, amlodipine 5 mg/d), pts with mean day-time ambulatory BP (dABP) > 135 and/or 85mmHg were randomized to receive, on top of these 3 drugs, either spironolactone 25 mg/d (D) or ramipril 5 mg/d (R) for 4 weeks. Then, treatment was increased either on W4, W8 or W10 if home BP was >135 and/or 85 mmHg: in D, furosemide 20 mg/d then 40 mg/d then amiloride 5 mg/d; in R, ramipril 10 mg/d, then bisoprolol 5 mg/d then 10 mg/d. Results: 169 pts were included: sex ratio M/F: 3.1; age 55 10 years; BMI 29 4 kg/m2; eGFR 82 18 ml/mn; dABP 150 13/92 10 mmHg (no intergroup difference). At W12: dABP was 128 11/80 9 mmHg in D and 141 17/85 10 mmHg in R; difference between groups (mmHg): 11.5 [CI95% 7.615.4] / 4.7 [2.27.2] (p < 0.001/0.0003); 68% were controlled (dABP < 135/85 mmHg) in D vs 28% in R (p < 0.0001). 19% needed uptitration until last step in D vs 55% in R (p < 0.0001). 7 pts in D and 5 in R discontinued the study due to drug related adverse events. At W12, only eGFR differed between D (69 18 ml/mn) and R (83 17 ml/mn) (p < 0.0001). Conclusions: Increasing sodium depletion by combining low doses of several diuretics induces a large and safe reduction in BP in resistant hypertension, and is more effective than RASB combination. PP.16.90 TREATMENT STRATEGIES FOR CARDIOVASCULAR RISK FACTOR MANAGEMENT IN PATIENTS WITH HYPERTENSION AND ADDITIONAL RISK FACTORS EXPERIENCES FROM THE USUAL CARE ARM OF THE CRUCIAL TRIAL

PP.16.88

NEW ANGIOTENSIN II RECEPTOR BLOCKER AZILSARTAN MEDOXOMIL: COMPARISON TO VALSARTAN

D. Sica1, W.B. White2, M.A. Weber3, G.L. Bakris4, A. Perez5, C. Cao5, S. Kupfer5. 1Virginia Commonwealth University Health System, Richmond, USA, 2 University of Connecticut School of Medicine, Farmington, USA, 3SUNY Downstate College of Medicine, New York, USA, 4University of Chicago Pritzker School of Medicine, Chicago, USA, 5Takeda Global Research & Development, Deereld, USA Objective: We compared azilsartan medoxomil (AZL-M), a novel angiotensin II receptor blocker (ARB) with another agent in the class, valsartan (VAL). Design and Method: In this randomized, double-blind trial, 982 patients received AZL-M or VAL daily for 24 weeks. At 2 weeks, intermediate doses were force-titrated to maximal doses (Table). The primary efcacy endpoint was change in 24-hour mean systolic blood pressure (SBP) by ambulatory BP monitoring (ABPM). Clinic SBP was also measured. Primary analysis was based on an analysis of covariance for change from baseline to week 24 or last treatment visit for AZL-M 80 and 40 mg versus VAL 320 mg. Hierarchical testing of noninferiority was followed by superiority to compare AZL-M and VAL. Responders were dened as SBP less than 140 mm Hg and/or SBP reduction of 20 mm Hg or more and DBP less than 90 mm Hg and/or DBP reduction of 10 mm Hg or more. Safety and tolerability parameters were also assessed. Results: The randomized subjects mean age was 58 years; 52% were men, 77% Caucasian. Baseline SBPs were similar (Table). AZL-M 40 and 80 mg lowered 24-hour mean SBP and clinic SBP signicantly more than VAL 320 mg (Table). Safety and tolerability were similar among treatment groups. Responder rates were higher for AZL-M 40 mg (50.2%) and 80 mg (54.7%) compared to VAL (41.3%; p 0.018 and <0.001, respectively).

A. Pavia Lopez1, J. Zamorano2, J.H. Kim3, S. Erdine4, A. Al Khadra5, M. Westergaard6, S. Sutradhar6, C. Yunis6. 1Hospital General de Mexico, Mexico, Mexico, 2Hospital Clinico San Carlos, Madrid, Spain, 3Catholic University St. Pauls Hospital, Seoul, South Korea, 4Cerrahpasa School of Medicine, Istanbul, Turkey, 5Prince Sultan Cardiac Center, Riyadh, Saudi Arabia, 6Pzer Inc., New York, USA Objective: The CRUCIAL study cluster randomization scheme aimed to recruit and maintain a true real-life Usual Care control arm, where treatment was entirely based on the investigators best clinical judgment.