162A ASH XI ABSTRACfS AJH-APRIL 1996-VOL. 9, NO, 4, PART 2 F89 F90 24hABPM daytime nighttime Key words: ambulatory blood pressure. oombination therapy. bellHllodters. angiotensin converting enzyme inhibttors A COMPARATIVE AMBULATORY STUOY OF CIlAZAPRIL COMBINEO WITH EITHER ISRAOIPINE, HYORQCHLOROTHIAZJOE OR BISOPROLOL e Vaisse, 0 Helj>in, S Boutelanl V Gressm. R Asmar. HOpltal de Ia TlIIIOl'Ie, Marseille, France. The purpose of tillS study was III assess with IIllbulaloly blood pressure (ASP) mollltoring, the eflicacy 01 cornblnabon therapy lithe 162 out of 407 patients (43%) With essential mIld III moderate hypertenSlOll which level of 24-11our ABP (NOV8COf 01 Space/abs, 96 measuresl24 hr) was hogh (> 139 01 87 mmHg, Staessen 1991) after a 6-week open lrealment WIth cilazapril 2.5 mg/day 00 (C). In thIS mulbcenler study, these non-respondets patients _e randomized III a double-blind lrealment WIth C cornbtned WIth 8Ither isradipine 2 5 mglday 00 (I), hydrochlorothlazJde 12.5 mglday 00 (H) or blsoprolol 5 mg/day 00 (B) for 6 additional weeks ABP was assessed Intent to treal analYSiS p < 0 05 P< 0 01 0.001 day 42 vs 84 . 6SABP P< 0.01 C+I VI C+ e, p < 0 05 C+Hvs C+B. 6DABP P< 0 01 C+I and C+HvsC+B We conclude that. althOUgh casual BP IS not different ABP data indICate that the combinabon of Cllazapnl and btsoprolollS more effective than that with isradlplne 01 hydrochlorothiazide aQaln at the end 01 thiS treatmenl phase (dav 84) Casual BP C+ Ifn =61\ C+HIn =461 C+B In =54} Oay42 SBP 162± 10" 160± 15- 158±15- OBP 97±10· 98 ± 10" 95±9- Day84SBP 153± 19- 152± 17"" 152± 16· OBP 92±9- 92± 11- 91 ±10- May SBP 8±14- 8±12'"" 6±17" 42-84 OBP 5±19- 6±10- 5±11- 24-hr ASP C+ I In =611 C+Hln=46) C+ BIn = 54) Day 42 SBP 148± 15 147 ± 11 148 ± 13 OBP 92±9 92±9 93±8 Day 84 SBP 142±13- 141±14- 137 ± 14- DBP 88±9- 89110- 84±8- 6day SBP 5± 10- 6±12'"" 11±11- 42-84 OBP 5±7- 4±8" 8±r- . - - A DOUBLE-BLIND COMPARISON OF PERINDOPRIL and ENALAPRIL ON 24-" CONTROL OF BLOOD PRESSURE IN HYPERTENSIVE PATIENTS. M Pego, J A Felizardo, A Santos, I J Martins Correia. Un. F. Qinica, Fac. Med Porto, Serviros OJrdiologia HU Coimbra, H PulidoValente Lisboa, Portugal. This multicentric, randomized, double-blind, parallel, controlled trial compared the antihypertensive efficacy and safety of perindopril (pER, 4-8mg/d) and enalapril (EN, 1o-20mg/d) administered (after 3 weeks on placebo) once daily for 8 weeks in patients with mild to moderate hypertension. Patients were included if on placebo, diastolic blood pressure (BP) was between 95-114 mmHg. PER 8mg/d or EN 20mg/d were used if after 1 month on the lower doses, DBP was still > 95mmHg. After 2 months 17 patients completed treatment with PER (7 on 4mg/d and 9 on 8mg/d) and I3 with EN (5 on IOmg/d and 8 on 20mg/d). There was no difference in age (53±7 v 50±9yrs) or in any demographic data within both groups. Ambulatory BP monitoring for 24h (ABPM) was performed on placebo (VO) and at the end of treatments (V2). Results (table) are mean (SEM). EN-VO EN-V2 PER-VO PER-V2 146I9S (613) 13S'/n, (713) 14S192 (312) m"/lS" (413) 1S419S (6/3) 142'/92' (7/4) 1S0197 (312) 138"/900 (4/3) 126/80 (6/4) 119/76 (514) 132/80 (5/J) 118"/73' (4/2) V2 .VO: I P<0.05.' P<O.02;. P<O.OI. Trough-to-peak (TIP) ratios (corrected for placebo) of both drugs were measured for systolic BP by two different methods: A- directly from curves that averaged all individual hourly 24h ABPM (TP of EN=O.54 and TP of PER=O.53) and B-averaging all individual TIP ratios after ABPM data were averaged for 3h intervals (TIP of EN=O.38±O.08 and TIP of PER=O.51±O.06. P=O.056). Five patients on each group reported mild side effects. We conclude that PER and EN have similar short term antihypertensive activity, although for the doses used PER is likely' to show a better TIP ratio. Key Words: Perindopril, enal april, efficacy, safety, trough. peak ratio. F91 F92 EFFICACY OF· LOSARTAN AS AN ANTmYPERTENSIVE DRUG ASSESSED BY AMBULATORY BLOOD PRESSURE MONITORING, BAND GRIP TEST AND ECBOCARDIOGRAPHIC STUDY. Maiorano G Bartolomucci F. Contursi V and Minenna F.S. Hypertension Group - Internal Medicine· University of Bari (ITALY) The effects of LOSARTAN (L), an orally active angiotensin n antagonist. on blood pressure monitoring, on the response 10 isometric stress and on the left ventricular diastolic funclJon, were studied in a group of IS patients (mean 49 ± SO ± 10.2) with nuld to moderate essential hypertension. The patients enrolled and admitted to the study should have received no previous antihypertensive treatment. After 3- week of observation period. L was adnulUstered once daily (SO mg) for a 8 week treatment period. Clinic and 24-hour ambulatory blood pressure (Spacelabs 90207 device), hand-grip exercise (Asimow Dynamometer, LA. CAl and echocardlographic study (Esaole AU3) according to the American Society of Echocardiography, were performed at the end of each period. The differences between pre-treatment and post·treatment periods were assesed by the Studenl'-test for paired observalions. Compared to the pre-treatmenl period, bolh systolic (SBP) and diastolic (DBP) blood pressure were significantly less at rest (rispectively p<O.Ol, p<O.OS) during the administration of therapy. Ambulatory blood pressure data, showed a significative reduction on 24-hour average of SBP and heart rate (HR) (p<;o.OS), but no differences were noted on OBP values Blood pressure response 10 isometric exercise showed no Significative d,fferences between pre and post-treatment period. All the patients refered no side effects dunng the treatment. Doppler-echo data showed no significative differences of Interventricular septum thickness, fractional shortening, systolic stress and sistemic vascular resistences. Our data mdicates thai Losartan SO mg/day was effective in lowering blood pressure values at rest, whtlst it does nol demonstrale the same efficacy to reduce DBP in 24-hour monitoring. The response to isometric exercise With hand-gnp lest, was not improved during treatment, probabily implying an inefficacy of the drug in stress conditions Losartan also caused a shghl bUI significant redUclJon in HR both during day and nighttime because it produced mh'bition of the vasoconstriction mduced by angIOtensin Ie II as ACE·mhlbitors bul Without significantly mlluencing the bradykinin-induced vas<"hlalion. This effect should be regarded as 8 favourable feature because of HR has been found to be 8 risk factor for cardiovascular disease and death Key Words: 24-hour blood pressure,Echocardiography.Hand Gnp Test.Losartan A NDI SEUX:'1'IVE ANrlllXNISf a 'nE (lNlAIN I'RESSCR unrr. P Fetrari, M. Ferran:1i, L. Duzzi, G, PllCi:lan1, I. MInotti, P. Mellon!. Tau, SettJJno M.ee, Milan, Italy Inaeased leYels of enr:Iogencus c:uabain-1ike factor (CU) have dEsnalstrated in experiJNrtal and genetic an1mal and in around JO' Of easent.ial hypertensi"" patients. Olronic infusial of 0Jabain (001 causes hypertension in rats. "n1us, au and ()J CXlU1d be phazmaoological targets for oow antihypertensive drugs. lie have synthetized a nev CXJl1XlUlX1 (PST 2238) tohich displaaos C1J frCJll the NaKAWase and it is clelIoid of inotrqrl.c activity and affinity for adrenergic, ca c:hanr>e1, Angio II and hoIm:Jnal steroid receptors. 'nle antihypertensive activity of PSf 2238 -.. assayed in rats with both experilrental, irdJced by C1J infusia\ (SO 'J'KgIdie " 4 _1<5; OS rats), and genetic hypertension sustained by inCreased levels of erd:lgenous eu (lollS rats). PSf 2238 vas c;iwn to OS uts at I, 10 and 100 y/I(q 011 for 4 _ks and to yaJn<J prehypertensive lflS at 0.1, 3 and 90 y/Ifq os for 5 _1<5, Systolic blood pressme (SI!P) and Mart rate (HI\) went recortIl!red weekly. I<id"ley na:itlla (KI, left ventricle (LV) and hypothalamic (Ilyl NaIOo'll'ase activity IMl'e measured at the end of treatment only in OS rats, PST 2238 re<lloed SSP in OS rats at all doses (-20 1II1flq, p<O.Ol). l( and LV NaXase activity increased in OS etr, (K. 2.55 1.1; LV. 0.2Jt.01 JII1lO1/11\l.n/m;l, p<O. 01) as lXJ!PBred to shaIlI aalire-infWled rats (K-1.471.15; jImOl/minlng). PSf 2238 at 100 y/Kg restored the NaI\a5e activity at the shaft· s 1e¥als in both tissues (K-1. 71.11, JII1lO1/1llin1Jrq}. In Hy the aJ-isoforlll NaKase activity 113S cllcreased in OS etr. (1. 441 .1 JII1lOl/Jllinlng, p<O. 01) as CQIll&red to shim rats (2.01±.36 jImOl/lllinlng), and returned toward the sham's l"""ls by PSf 2238 bct.h at 1 (1. 92 1 0.01 JII1lO11111in1ng1 and 100 y/Kg (1. 79 1 0.1 jlIlO:>1/minlngl. In lflS PSf 2238 re<lloed in a dose-dependent way the develClplWlflt of hypertension (-5. -12-, -16- 1IIItlg, 0.011. In ocn:lusion PST 2238 is a prototype of a new class of anUhypertensi". <:IJ:U1s tohich at very 1"" doses selectively antagcnizes the pressor effect of C1J or a.z by interferrinq at the level of the NaK An-sse.