H54 Efficacy and safety of candesartan cilexetil in combination with hydrochlorothiazide (HCTZ) in the treatment of patients with mild to moderate hypertension unresponsive to HCTZ alone

9

ASH XII ABSTRACTS

A]H-APRIL 1997-VOL. 10, NO. 4, PART 2

H53

H54

COMPARISON OF THE ANTlHVPER7ENSNfE EFFtCACVOF CANDESARTAN CILEXETILVERSUS PtACESOOR ENALAPRLIN PATIENTS WITH MILOTO MODERATE ESSENTfAL 16VPERTENSION

EFFICACV ANOSAFETVOF CANOESARTAN CILEXETILIN COMBINATION WTTH HVDROCHLGROTHIAZIDE (HCTZ) IN THE TREATMENT oF PATIENTS WtTH MILD TO MOOEFIA7E HVPERTENSN2N UNRESPONSIVE TO HCTZ ALONE

AZancheEti, ~

and C Oi Biagio. university of Miian, Milan, ltsly. ~

This phsss Ill, mulfkenkr, dcubJa-blind,rsndwnind sfwdywas pufwrnedt.a primafiiywmpare theantlhypwtensiw efocscyofcandsssrfsn cikxefilwifh placaba in paflenkwifh mildtomcdwate hype!tenslon(sittingDSP 95-10S mmHg). A comparisonwilhthe refersncadmgenalapril and am feyandtolemml~ ana~h were alsa included.0fthe227 paflantsag9d 18-70 ~rsenmNed in a 4W placeborun-inpha~, 2C60Ngit4apdtlentswrssub8squsniiy rmd0m!se2 fOS waeks, Para!hltreatman twithUnwtian cikxefil (SO),placaka (44) oremlapril (81), A doublingofd-asaga,from 4t0S mg Onesdaiiyfor candasartancllexatiland fr.an Iotorn mg .mce dai~forenalapril, was presorted aSer4w-eeks7tresfimnf f sdfingDBP remainad=Sd mmHgorthe DSP reductioncomparedto ba8ditwwas .8mmHg, Bkodprse-Wreme asuremmtswero pmformsd24hourspmtdose Om3age.doubiingws8neces.smya tler4vmeks in 43.2% ofplawbo patients,3S7% ofcandesartan cikxetll patiemsand 28.2% ofenalspdl patients.Mea” reducthi” sittingDBP frcfn baseliWwere6.3 mmHg fcfplaceba, 10.1 mmHg forcandesatin ciksetil (P.O.0$ vs placeka) and 10.5 rnmHgforenalap_il(p
Key words:

Candewfan
enalapril,antihypertensive-eh7Cq.

E Reti and SG Magin. Psris VI University, Paris, France.

325 pstienfswed l&70 yarstih mitdtomtiwsfse ssmtial hyptension (sMing DBP95-10SmmHg)were enrolledihtofhis rand.nnked, daubls-bll,?d,mutiicanter, placebmmtml!ad Studyt.aassessthe atilh~e”she ewandtdemtil~ of candessrlsncitaxsfilsddedto HC7Z in pstlonfaunrqnsiveto HCTZ I?mnofhwapy,AIWa &waskplacsba nm.in Podcdacd 6wmeksttreatmanlWlh HCTZ monotherapf Z34n.nnespcmsive patkntswere mndomisedto HCTZ 12.5 m#day + ptaceb.a(@), HC7Z 12S mg + candsaman cikxetil 4 mg/day(94) or HCTZ 12,5 mg +candssartan cil.sxefilS mg/day(91) for 6wssks. Blocdpressure measurementswre mad.e24hours post-dose. After 4weeks, treatmentwtthplacebo sittingDBPWSS telcwththreshold for study continuation(44mmHg) in 9% of the original325 patients.Furthermore,6% of262 patienfsti.arked 6v.eeks HC7Z mmafherapy had normalisedDBP (sS9 mmHg). Resuiisofthe intention-tstreafanaiysis(lT7)v.mfe simllartothoseof the per-pmtcd anaiysia Fuflhermduetions (IT7) in mean sittingDBP from basdinewere: HCT2 + placebc.,3.3 rnmHg; HCTZ + Gandesartancilexetil4 mg, 7 mmHg: and HC7Z + Candesafianoilexetil8 mg, 7.9 mmHg, The,ewas a signitintoverall inkrgro”pdiffemnce in these rewts (2.sided ANOvA; p=0,0361) and an estimatedaddkionalDBP.!.aweri”geffect of3.9 nvnHgw-as providedby candesmtancilexstil4n&T(p=O.0127 vs HCT2 + placebo)and 5 mrnHgwtih candessrta” citexetilB mg (p=O.C017vs HCTZ + placetm)wher!added to HCTZ 12.5 mg. There Wasno Qgnifcant differencein this measure betwsemcandesartan cilexetilgroups Responssrsfea (based cma decrease in stiing OBP ofzlo rnmHg or reductionof sittingDBP to sS9mmHg)were: HCTZ + pkcet.a, 32.7%; HCTZ + candsswta”cikxetil 4mg, 4S8%; HC7Z + Csndessdsndlemfil S mg, 53.S%. 3ttiistiml~ signifi~”tr&Wti”s rdativeto placekv,nre also recordedfcjrsitting SBPwith HCTZ + candesarfancilexetll4mg (p
KeyWords:

Candesmtamcilexetil,hydrc-shlorothi~ide,combination-therapy, antihypetiemsive.erfirjacy.

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OOSE-FINOING STUOV OF CANOESARTAN CILEXETILANO HYDROCHLOROTHIAZIOE IN COMBINATION IN PATIENTS WfTH MILOTO MOOERATE HYPERTENSION

COMPARISON OF THE EFFICACY AND SAFETY OF CANDESARTAN CILEXETIL4, 8 AND 72 MGViSTH PLACESOANO ENALAPRfL IOMG IN PATIENTS WITH MILD TO MODERATE Essential HYPERTENSION

~,

H Lekel a“d H-J Arms. University of E~en,

Essen, Gemny.

To determine whether the antlhyperfensiveeffed ofcandesaftan cilexetlli“ combinationwith hydrtmhlorothiazide(HCTZ) is suwriorto that cdakherdrug alone, 1306 patients aged 1S-75 yewswth mild to modsrate hyp-ertenskm (sittingOBP 295-s110 mmHg) were WIml)sd in this double.blind, randomud, placsbo-controlk.d,multicenter,factorialdesign, phase II study. Aflera 4-wssk placebo run-in p+ricd, 109s patients were randomissd to trsatmentwih combinationsOfO, 2, 4, 8 or 16 mg candesartm C&exetiland O, 12.5 CW2Smg HCTZ for 8 wseks. 1030 patients were included in the inb?ntion-t.a.trwat (llTI analysis and 89S in the p+protocol (PP) analysis. Overall, the greatest mean reductions(least squsres means) in sitting DBPwsre assoc!akd with candesartan cilsxeO 16 mg and the grsatest decrease mlativeto baseline (16.6 mmHg) was sssn with candessrtan ci!exetil16 mg/HCTZ 12.5 mg. Other notable reductionswere 13.t mmHg (16 mg/25 mg), 10.7 mmHg (8 mg/25 mg),10.2 mmHg (8 mg/12.5 mg) and 10.1 mmHg (4 mg/12.5 mg), Confirmatov analysis Ofmmparisons of each combinationviith individual components and placebo (llT) showsd the 6 mg125mg combinationto be s.periorto candesartan cilexetil8 mg (P=0,0249), HCTZ 25 mg (P=O.0C44)and placebo (P=O.0000). Other combinationswith significantl ygreatereftlcscythan individualcomponents (maximum pvalue from pair of tests shown for each combination) and placebo aflerdescriptive analysis wsre Csndasattan cikxetil 4 mg/HCTZ 12.5 mg (P=O.0108 and 0.0001, rsspecfively)and Csndesatian cilexetil 16 mg/HCTZ 12.5 mg (P=O.0D45 and 0.00Q0, respectively).All combinationsexcept candesartan cilexetil2 mg/HCTZ 12.5 mg were statistically significantlys.periorto placebo. The incidence of adverse events (influenza-likesymptoms were most common) increased when HCTZwas added to candesartan cilexetil4 mg, S mg and 16 mg, Adverse events were experienced by 24% (candesarfan Cilexetil 2 mg/HCTZ 25 mg) to 40% (candesarfan cilexetil 16 mgfHCTZ 25 mg) of patients. There were no ma!ked diffsremxts in the qualify ofadverseevants between groups. 2.4% of all patients withdrswfrom the study. Laboratowand ECG resultswere slmilarfor all groups. In summary combinationsofcandesartsn cilexetil/HCTZwsre supetiorto monotherapy - candesartan cilexetil 16 mg/HCTZ 12.5 mg being most effacfivs, followed by respective combined doses of 16 mg/25 mg, 8 mgL?5mg, 6 mg/12.5 mg and 4 mg/12.5 mg. Increasing the HCRdose to 25 mg in combinationwith candesatian cilexetil 16 mg did nOtreduca bloc%pressure fwtherthan HCTZ 12.5 mg. Candesarlan Cilexetilwas well tolerated by patients in this study. Key WOrds:cande~afla”.cilexetil, hydrochlorothiazide,combination-therapy, antihypertensive-eficscy, factorialdesign.

~, WM Hern’nmm and SG Magin. Cemre for Oialysk, Saarl.auis, Germany. TheantihWensiw efF&&cyand saretyofcandeswfm cikxetil (4, 8 and 12 rng Oncedaiiy)Wascomparti wththatof placeboorenalapdl (10 mg once daiiy) Inthia 12-week, randmnized,double-blind,muiitcenterstudy 3S0 patientsaged <&70 yearstith mildtommfemteeesential hyp.wtension(sittingDBP SS-lt4 mrnHg) were recruitedand Wcd pressuremeasurementswere performed24hwra ~t. dose. 32S PatientswWeavailablefor intentio”totreat (ITT) a“aiysis (F+a.ebo. 5s, enalapril= 7t, Candasattsncikxstil4mg = S3, B mg = 5Sand 12 mg = 65) which shuwedchan~insitfing DBP from baselineafier 12weeks, treatmemto ba: candssartancilexdil 4mg, 4,4 mmHg (p=O.07 vs placeba);8 mg, -tO.5 mmHg (P
KeyWords:

Candesarta..cikxetil, enak~il, antih~etie”siv~e fficacy.