Irbesartan safety and effectiveness: a post-marketing surveillance study

120A

ASH XIV ABSTRACTS

AJH-APRIL

DO37

1999-VOL.

12, NO. 4, PART 2

DO38

OF AT- 1 RECEPTOR ENDOTHELIUM - DERIVED FACTORS HYPERTENSION. INFLUENCE

BLOCKADE ON IN ESSENTIAL

INHIBITION LOSARTAN

OF SYMPATHETIC ACTIVITY INDUCED IN ESSENTIAL HYPERTENSIVE%

S. Cottone. A.L. Neri. M.C.

Vella,

A.

Vadall.

R.

Riccobene,

BY

and

G.Cerasola. Istituto

di

University It (NE)

Medica

Clinica

of

Palermo,

is established

release

by

that

activating

In the present evaluated the effect

Epinephrine (E) and

e

Malathe

Cardiovascolari.

ITALY.

Angiotensin prejuncrionat

II can enbanco AT, receptors.

norepinephrine

study in 12 mild essential bypertensives was of Losnrtsn on plasma tevols of NE and on blood pressure (BP). both in basal condition

and at the wane of a handgrip test. The lest was carried ou, under placebo treatment and afrer 0”s and two months of losartan-therapy (50

mglday).

Our results show that chronic blockade of AT, receptors induced losartsn in essential hypertensives leads to a decrease in basal by sympathetic aclivity and blunts sympathetic reactivity to stress. It is conceivable that this result is due to the inhibition of prejunctionsl AT 1 receptors. Thus. this effect may represent a further useful therapeutic outcome in hypertension treatment.

KEY WORDS

:

ENDOTHELIAL FACTORS, AT-I BLOCKERS, ESSENTIAL HYPERTENSION

DO39 SIJRVEJLUNCE

STUDY.

w

JS Park, K Reilly. J

Trkwi* for the AST investi@ors. Lnuisville t&tab& and Athemsclenwir Raearch Centa, L&will% KY. Irb*lsrtan, . potent, loogscting m&enaion 11receptor blocker withabigbrlslivityfmATlRlbtypcrrceptor*wutatedinr multicmter.opm-l&labe1.pr&i~trialu*4ga~oflSOmg admitliatucdalced.¶ilyfor4melrr. Tbepuqweofthestudywto c.xamktltcatltib~~etTe%i-mullafetyof~fa tmabnentofhypstenajmia~hodMgedsubj& lke-tbausmd thwhur&edelewcentusweretr&ered~11,783patimtr~ mmllcd~Eigainginformalemrnt Patientswactobcmalea fanalc,lE~ot~ooldawithabr+liocScDBPbchnea9 llSlnmB& ofthepatk&auolkd,7314wseeoa*dcrrdevduaMefar the cffiwy analysa and 9009 sue evaluable for the say analysis. Fmm&alinetoeodpointovathc4-wccl;study.ptia\trcxpricnccda tedwtion in sated diastolic blood pmswe (SeDBP) of 9.4 mm Hg (95% carfidena bltaval: -9.7. -9.1) and. meall Ieduction in se&d systolic blood presmuc (SeSBP) of 1~5.9 mm Hg (-16.3. -15.4). Subgmup aMlyaa~tcdti~rcducti~i,lscD~~of~e,

Markedre&timcinscDBPuuec*perislcedby p&XltSWhO~lUWlydiagnooed~tihad~~ewrurd c.aihyputauive mcdicatimq -13.3 mm Bg (-13.8. -12.8) and-13.9 mm Bg (-14.4, -13.5). lrspaivcly. subjects who had &bfailx SeDBP ofa llOmmHghadtkgratesIredwtiminSeDBP. ‘Ihmeanchange~ baaeliw for tbir nubglmp wu -21.2 mm Hg (-22.2, -20.1). OvMlll, 77%0fpatientswaccLktiedu~(scDBP<9ommBgaa10 mmHgmdwtion6mmbaselicc)and66%wreraonnalLcd(ScDBP< 9Omm IQ). A total of 1232 (13.7%) puimta in this nos-plubo cmtmlled trial experienced 1766 advase evada, 1257 (71%) ofwhich waccauidacdrelataito8huiy~ Themajciityotdwneevent8 cbwiticd by iwwtigatm were mild in severity with halack, 1.8% (Cr: l.6%,2.1%)anddizinm, lJ%(CI: I.7%.2.2%)beitqthemost umnnon. Ei&dy-five patimts (0.9% ofthe evaluable safety pqulation) repmtedl19aeriousadvuae~ta oftheevaltsq!ortedinthcde patients, 20 (0.2%) wcr~ Eanudacd by the investi@w to be pouibly, p&ably* Q detblitely related to tbe study drug. ovaall. this study drmc&&dtbatirbcrartrmgivcaonccdai1yattbcdar(iogdoaL?of 15Cmg ir uI etktive and wll-talemted antihypatmsve qatt race.a~ada.

Key Words:

WORDS

: CATECHOLAMINES, ATI- BLOCKERS, ESSENTIAL HYPERTENSION

DO40

lRBESARTAJiSAFZIYANDEFFECTIVENESS:APOSTMARKElwo

KEY

IrbeMltm. att@ainn~tianiagdg mtihypfdmsive dl-lacy. ddy

Long Twm Eflca~y, SW, and Tolembillty of Candoaatin CIIeXetll Added to Hydrochlorothiarlde In Patients Wlth Swore Syntamlo Hypertension Suzanne Oparil. Edc L. Michelson. University of Alabama at Birmingham. Birmingham, AL, Astra Pharmaceuticals, Wayne, PA for the Candesartan Cilexetil Study Investigators Efficacy. safety and tolerability of the potent angiotensin II receptor blocker candesaltan cilex@l (CAND) were evaluated in a 4 week. multicenter. randomized double-blind, placebo-controlled study of patients with severe hypertension (JNC VI: Stage 3) falbwad by a 48 week open label extension (OLE). Patients with sitllng diastolic blood pressure (DBP) t 110 mmHg were treated with HCTZ 12.5 mg once dailv (QDl for 1 week. Those with DBP z-95 mmHo after HCTZ run-in wer;, &io”lzed to CAND 8”3 QD or placebo, pi&z HCTZ 12.5 “79, and uptitrated as necessary. to CAND 16 mg Qo or matching placebo plus HCTZ 12.5 “g ClD to control DBP (< 90 mmlig). Patients who completed the 4 week double-blind phase were eligible to enter the 48 week OLE; 143 patients entered OLE and received 8 “g CAND plus 12.5 “g HCTZ, titrated to 16 mg CAND and then 25 “g HCTZ as necessary to control DBP. Results for the 141 patients with efficacy data:

Overall. 89043 patients (62.2%) received CAND 16 “g + HCTZ as final treatment and only 28043 (19.6%) were discfmtinued for lack of efficacy. Of the 70 patlents completing the OLE. 61 (87.l%)wem responders (DBP < 90 mmHQ or &? 10 mmHQ from double-blind enby) and 47170 (67.1%) patients were contmlled. Effective reductions @O.O96.6%) were seen acmss age. race and sex subgroups. A total of 15 patients (10.5%) discontinued due to adverse events. although most were not considered drug related. Conclusion: The addition of candasartan cilexetil to HCTZ is hiihly effective and has a” excallent safety and tolerability pmftle when used in the long term treatment of patients with severe hypertension (JNC VI: stage 3). Key Words: Candesaftan Cilexetil. Anglotensln Hydmchbmthiazide. Severe Hypertension

II Receptor Blocker.