- Email: [email protected]
H46 Is reversion of arterial abnormalities in treated hypertensive patients an important aspect? Use of an ace inhibitor (Perindopril) in a large international trial — the complior study
88A
ASH XII ABSTRACTS
AJH-APRIL 1997-VOL, 10, NO. 4, PART 2
H45
H46
CANDESARTANCILEXETfL 16MG PROVIDESGREATER ANTIHYPERTENSWE EFFECTTHAN LOSARTAN50MG m PATIENTS WITHMILDTO MODERATEHYPERTENSION 9.K. Andersson , Sahlgrenska University Hospital, Gothenburg, Sweden
IS REVERSION OF ARTERIAL ABNORMALITIES IN TREATEO HYPERTENSIVE PATIENTS AN IMPORTANT ASPECT ? USE OF AN ACE INHIBITOR (PERINOOPRIL) IN A tARGE INTERNATIONAL-TRIAL THE COMPLIORSTUOY R. Asmar’, J. Tcpouchian, AC, Potccka, Ch, Charpentier, B, Levy ME, Safar Insfittitd+?Rechemhe et Formation Cardiovasculaira Paris. France Motiidity and mortality in treated hypertensive patients are mainly determined by large arteries lesions tiich may occur in different organs and circulations (coronary, cerebral, renal ...). These struchtral and fundicmai changes of the arterialwall madia and alterations of vascular enrkihelium are usually obsewed at eady stage of hypertension, all l~diW to an increased stiffness of the an?pafily related to elevated arterial wall. Althmqh alterations of large arteries BP, other factors have been found to stimulate arterial VA hypertrcphy and stiffness during hypertension, This increase in arterial stiffness is responsible for an inadequate incraase in systolic blcnxl pressure and a relative decrease in aortic diastolic blcod preasure, and causes an increase in arlerial pulsatility and a disprq?mfionate incrsase in end-systolic stress, promoting development of cardiac hyparfrcphy, increases ventricular oxygen consumption and left ventricular hypartrcphy, and thus compromises capacity of coronary perfusion, Since clinical and qicksmicdcgical studies have mised the possibility that stiffening of large arterfes ia aaaociated Wh excess morbidity and mortality Independently of mean blood pressure : and since studies of pharmacological qents cleady indicate that for the same blood pressure reduction, Iatge artariaa alterations may b prevented or reverse to a greater or lesser extend, dependimg onthet~of antihypertensive compound, it is important to evaluate tha ability of antihypwtensive treatment to reverse arterial abnormalities chewed in untraated h~rtenaives, Attgiotensin converting! enzyme inhibitcm (ACEI), by acting on the reninargiotensin system in plasma and tiasue, and on the bradykinin NO system, have besn stggested to impmve arterial alterations. These clinical data lead to a new concept for hypeflension treatment, In this rsgard, the Complior tidy, a multicentric international study, was kigned to evaluate chronic effects on arterial stiffness of 6 months treatment with pertnckpril (4 to 8 rmjday), This study, perfomwd in out+afients with mild.to-moderate h~rtension allows the evaluation of arterial stiffness chaWe$ under antihypertenaive treatment and tha intfmrtanca of its applications in lametrials based on clinical approach,
and S. Neldam, Rodovre, Denmark, for the MC Study Group Candesartan cilexetil (canal. cil.) is a novel angiotensin 11 antagonist, selective for type 1 receptors. Due to its tight binding to and slow dissociation from the receptors, adminis~ation of canal, cil, results in a dose dependent and long lasting antihypertensive effect. Losartan was the first angiotensin 11 antagonist to be approved for the treatment of hypertension. The usually recommended dose of Iosartan is 50 mg once daily and higber doses do not seem to result in furtber blocd pressure (BP) reduction. This study was performed to compare the antihypertensive effect and tolerability of canal. cil. 8 or 16 mg once daily with that of placebo and of Iosartan 50 mg once dcily in patients with mild to moderate primary hypertension. Men and women, aged 20-80 yecrs, with primary hypertension and sitting diastolic BP 95-114 mmHg at the end of a 4 week placebo run-in period, were randomised to once daily (o.d.) double-blind treatment with canal. cil. 8 mg (n=82), canal. cil. 16 mg (n=86), Iosartan 50 mg (.=84) or placebo (.=85) for 8 weeks. Sitting BP was measured 6 and 24 hours after dose, i.e. at time of peak and trough effects. The primary effect variable was sitting diastolic BP at trough. The differences between treatments in BP change from randomisation to the end of the study were analysed by analysis of variance. At randomisation, mean sitting diastolic BP at trough for all treatment groups ranged from 102 to 104 mm Hg. Compared with placebo treatment, diastolic BP was significantly reduced at trough by a mean (95% CI) of 8.9 (6.0;1 1.8) mmHg witb 8 mg and 10.3 (7.4; 13.2) mmHg with 16 mg canal. cil. The comesponding reductions at peak were 7.6 (4.6; 10.6) mmHg and 10.6 (7.6; 13.7) mmHg, respectively. Canal. cil. 8 mg wcs as effective in reducing sitting diastolic BP as Iosartan 50 mg and the 16 mg dose was significantly more effective than Iosarlan at trough, witb a mean difference of 3.7 (0.8;6.7) mmHg (P=O.013). The placebo-corrected troughlpeck ratios for sitting systolic and diastolic BP were close to I with canal. cil. and approximately 0.7 with Ioscrtcn. Both 8 and 16 mg canal. cil. were at least as well tolerated as Iosartcn and similar to placebo in this respect. In conclusion, canal. cil. 8 or 16 mg o.d. is an effective and well tolerated antihypertensive treatment, Canal. cil. 16 mg is significantly more effective than Iosartan 50 mg o.d,, 24 hours after dose administmtiom Key Words:
Keywords hprtension
candesartan cilexetil, Iosartan, antihypertensive efficacy, tolerability
: antih~rtensive
drugs, arterial
stiffness,
ACE
inhibitor,
H47
H48
INSIGHT: BASELINE CHARACTEFGSTICS MJBrownl, A. Ccstaigne2, PW de Leeuw3, G. M cncisa4,T. ROSentba15,LMRuilope6 IAdd~br~ks Ho~ital Cambrid e 2Hospital Hemi Msdor (keteil, 3Accdtic Hospital Maastricht, f’Umvcrsdd degli Studi MilmO, 5ChafiM~ic~ Cat= TelH~h~m~, 6Cmetma &A&lucia
FACTORS PREDICTING BLOOD PRESSURE RESPONSE TO BODY WEIGHT LOSS THE HARVEST STUDY. M. Wimickl “$, M. Santonastaso, E. Cozzutti, M. Dal FoOO, G. Berron, P. Palatini on behalf of the HARVEST Trial Group, Italy. Clinica Medica I, University of’ Padova, Italy, and ‘Department of Hypertension and Diabetology Medical University of Gdansk, Poland. We investigated how changes in body weight (BW) affect office cnd ambulatow blood pressure (BP) and if BW changes are related to baseline catecholamines in hypefiensives with positive (FH+) and negative (FH-) family history of hypertension. In 744 borderline to mild hyperrensives (535 men and 209 women) participating in the HARVEST study 24-h urine catechokimines, otike cnd ambukwmy BP (Ac%D TM2420 or Spacelabs 90207) were measured. Ovenveight subjects were advised to decrease calorie intake. After 3 months ambulato~ BP measurement was repeated. Subjects were divided into two groups, according to whether their BW decreased (Gl) or not (G2) cnd by FH stares (GIFH+, n=l 18; GIFH-,n=203; G2FH+,n=178; G2FH-, n=245). All subjects were also divided using mean urimxy dopamine level as a tresbold value (572 #g/ml124hour). After 3 months BW decreased by 2.7i0.lkg in GI and increased by l. OtO.lkg in G2. Witbin the two groups, FH+ cnd FH- subjects chcnged BW to a similar extent. Office BP fell to a similar extent in the two GOUPS, while ambulatory BP showed a decrease only in GI in comparison with G2 (SBP = -1.8+ 0.5 vs +0.3+ 0.4mmHg, P=0.003; DBP = -1.7+ 0.4 VS O.t)+tl.hndfg, p=O.OO1). GIFH+ subjects sbowed a gfeater response of 24-h BP to BW loss tban 31 FH- (DBP=-2.5*0.5 VS 0.6+0 .6mmHg, P=0.04; SBP=-2.5+0.7 VS 0.8*0 .8mmHg, p=ns). In comparison with G2, only GIFH+ subjects showed a significant decrease in SBP (P=O.03) and DBP @=O.Ot). A negative correlation was found of BP changes with dopamine level (SBP I= -0,135, P=O.024; DBP r -0.119, p=O.047) in FH+ subjects but not in FH- subjects. fn a two-way ANCOVA, FH status cnd urinary dopandne (in a negative fashion, rO.046) were predictive of the weight-related BP fall. Moreover, an FH-dopamin interaction was found on the effect of weight loss (p=O.05). In fact, onfy FH+ low dopamine subjects showed a significant decrease in 24-hour ambtdatoty DBP in comparison with FH+ high dopamine subjects and with FH- groups. fn conclusion weight reduction in mild hypertensive is effective mostly in patients with FH+. Detection of low dopamine values is an additional reason for recommending BW loss in these subjects.
Madrid In INSIGHT a total of 7,428 hypertensive atients with at least one additional risk-factor were,reqmted and 6,5 ! 8 randomized to &ubleb~d@imentwitbci tbermfed,pine once-daily ?rhydmcblorothiczide / amdonde. ,Primary endpoints We mywxdud infarction, stroke, subcracbnold hemorrhage, congestwe heart failure, and sudden dcatb. Rmuitmentstarfed ~ Septembex 1994 andwcs finalized in April 1996. Treatment duration M 3 -4.5 years. Therefore results cre expected in 1999.5 diflerentsde-cnn studies will estabbsbthe relationship between hypertension, progression of atherosclerosis, end organ damage, cnd critical events.
Hm
E Sweden
182
Denmark
133
Norway
71
Total
6588
Key Words:
Proteimtria
2Y0
nifedipine, outcome, hypcrtcnsimt
1
Key worda: hypertension,heredity,obesity,dopamine
ASH XII ABSTRACTS
AJH-APRIL 1997-VOL, 10, NO. 4, PART 2
H45
H46
CANDESARTANCILEXETfL 16MG PROVIDESGREATER ANTIHYPERTENSWE EFFECTTHAN LOSARTAN50MG m PATIENTS WITHMILDTO MODERATEHYPERTENSION 9.K. Andersson , Sahlgrenska University Hospital, Gothenburg, Sweden
IS REVERSION OF ARTERIAL ABNORMALITIES IN TREATEO HYPERTENSIVE PATIENTS AN IMPORTANT ASPECT ? USE OF AN ACE INHIBITOR (PERINOOPRIL) IN A tARGE INTERNATIONAL-TRIAL THE COMPLIORSTUOY R. Asmar’, J. Tcpouchian, AC, Potccka, Ch, Charpentier, B, Levy ME, Safar Insfittitd+?Rechemhe et Formation Cardiovasculaira Paris. France Motiidity and mortality in treated hypertensive patients are mainly determined by large arteries lesions tiich may occur in different organs and circulations (coronary, cerebral, renal ...). These struchtral and fundicmai changes of the arterialwall madia and alterations of vascular enrkihelium are usually obsewed at eady stage of hypertension, all l~diW to an increased stiffness of the an?pafily related to elevated arterial wall. Althmqh alterations of large arteries BP, other factors have been found to stimulate arterial VA hypertrcphy and stiffness during hypertension, This increase in arterial stiffness is responsible for an inadequate incraase in systolic blcnxl pressure and a relative decrease in aortic diastolic blcod preasure, and causes an increase in arlerial pulsatility and a disprq?mfionate incrsase in end-systolic stress, promoting development of cardiac hyparfrcphy, increases ventricular oxygen consumption and left ventricular hypartrcphy, and thus compromises capacity of coronary perfusion, Since clinical and qicksmicdcgical studies have mised the possibility that stiffening of large arterfes ia aaaociated Wh excess morbidity and mortality Independently of mean blood pressure : and since studies of pharmacological qents cleady indicate that for the same blood pressure reduction, Iatge artariaa alterations may b prevented or reverse to a greater or lesser extend, dependimg onthet~of antihypertensive compound, it is important to evaluate tha ability of antihypwtensive treatment to reverse arterial abnormalities chewed in untraated h~rtenaives, Attgiotensin converting! enzyme inhibitcm (ACEI), by acting on the reninargiotensin system in plasma and tiasue, and on the bradykinin NO system, have besn stggested to impmve arterial alterations. These clinical data lead to a new concept for hypeflension treatment, In this rsgard, the Complior tidy, a multicentric international study, was kigned to evaluate chronic effects on arterial stiffness of 6 months treatment with pertnckpril (4 to 8 rmjday), This study, perfomwd in out+afients with mild.to-moderate h~rtension allows the evaluation of arterial stiffness chaWe$ under antihypertenaive treatment and tha intfmrtanca of its applications in lametrials based on clinical approach,
and S. Neldam, Rodovre, Denmark, for the MC Study Group Candesartan cilexetil (canal. cil.) is a novel angiotensin 11 antagonist, selective for type 1 receptors. Due to its tight binding to and slow dissociation from the receptors, adminis~ation of canal, cil, results in a dose dependent and long lasting antihypertensive effect. Losartan was the first angiotensin 11 antagonist to be approved for the treatment of hypertension. The usually recommended dose of Iosartan is 50 mg once daily and higber doses do not seem to result in furtber blocd pressure (BP) reduction. This study was performed to compare the antihypertensive effect and tolerability of canal. cil. 8 or 16 mg once daily with that of placebo and of Iosartan 50 mg once dcily in patients with mild to moderate primary hypertension. Men and women, aged 20-80 yecrs, with primary hypertension and sitting diastolic BP 95-114 mmHg at the end of a 4 week placebo run-in period, were randomised to once daily (o.d.) double-blind treatment with canal. cil. 8 mg (n=82), canal. cil. 16 mg (n=86), Iosartan 50 mg (.=84) or placebo (.=85) for 8 weeks. Sitting BP was measured 6 and 24 hours after dose, i.e. at time of peak and trough effects. The primary effect variable was sitting diastolic BP at trough. The differences between treatments in BP change from randomisation to the end of the study were analysed by analysis of variance. At randomisation, mean sitting diastolic BP at trough for all treatment groups ranged from 102 to 104 mm Hg. Compared with placebo treatment, diastolic BP was significantly reduced at trough by a mean (95% CI) of 8.9 (6.0;1 1.8) mmHg witb 8 mg and 10.3 (7.4; 13.2) mmHg with 16 mg canal. cil. The comesponding reductions at peak were 7.6 (4.6; 10.6) mmHg and 10.6 (7.6; 13.7) mmHg, respectively. Canal. cil. 8 mg wcs as effective in reducing sitting diastolic BP as Iosartan 50 mg and the 16 mg dose was significantly more effective than Iosarlan at trough, witb a mean difference of 3.7 (0.8;6.7) mmHg (P=O.013). The placebo-corrected troughlpeck ratios for sitting systolic and diastolic BP were close to I with canal. cil. and approximately 0.7 with Ioscrtcn. Both 8 and 16 mg canal. cil. were at least as well tolerated as Iosartcn and similar to placebo in this respect. In conclusion, canal. cil. 8 or 16 mg o.d. is an effective and well tolerated antihypertensive treatment, Canal. cil. 16 mg is significantly more effective than Iosartan 50 mg o.d,, 24 hours after dose administmtiom Key Words:
Keywords hprtension
candesartan cilexetil, Iosartan, antihypertensive efficacy, tolerability
: antih~rtensive
drugs, arterial
stiffness,
ACE
inhibitor,
H47
H48
INSIGHT: BASELINE CHARACTEFGSTICS MJBrownl, A. Ccstaigne2, PW de Leeuw3, G. M cncisa4,T. ROSentba15,LMRuilope6 IAdd~br~ks Ho~ital Cambrid e 2Hospital Hemi Msdor (keteil, 3Accdtic Hospital Maastricht, f’Umvcrsdd degli Studi MilmO, 5ChafiM~ic~ Cat= TelH~h~m~, 6Cmetma &A&lucia
FACTORS PREDICTING BLOOD PRESSURE RESPONSE TO BODY WEIGHT LOSS THE HARVEST STUDY. M. Wimickl “$, M. Santonastaso, E. Cozzutti, M. Dal FoOO, G. Berron, P. Palatini on behalf of the HARVEST Trial Group, Italy. Clinica Medica I, University of’ Padova, Italy, and ‘Department of Hypertension and Diabetology Medical University of Gdansk, Poland. We investigated how changes in body weight (BW) affect office cnd ambulatow blood pressure (BP) and if BW changes are related to baseline catecholamines in hypefiensives with positive (FH+) and negative (FH-) family history of hypertension. In 744 borderline to mild hyperrensives (535 men and 209 women) participating in the HARVEST study 24-h urine catechokimines, otike cnd ambukwmy BP (Ac%D TM2420 or Spacelabs 90207) were measured. Ovenveight subjects were advised to decrease calorie intake. After 3 months ambulato~ BP measurement was repeated. Subjects were divided into two groups, according to whether their BW decreased (Gl) or not (G2) cnd by FH stares (GIFH+, n=l 18; GIFH-,n=203; G2FH+,n=178; G2FH-, n=245). All subjects were also divided using mean urimxy dopamine level as a tresbold value (572 #g/ml124hour). After 3 months BW decreased by 2.7i0.lkg in GI and increased by l. OtO.lkg in G2. Witbin the two groups, FH+ cnd FH- subjects chcnged BW to a similar extent. Office BP fell to a similar extent in the two GOUPS, while ambulatory BP showed a decrease only in GI in comparison with G2 (SBP = -1.8+ 0.5 vs +0.3+ 0.4mmHg, P=0.003; DBP = -1.7+ 0.4 VS O.t)+tl.hndfg, p=O.OO1). GIFH+ subjects sbowed a gfeater response of 24-h BP to BW loss tban 31 FH- (DBP=-2.5*0.5 VS 0.6+0 .6mmHg, P=0.04; SBP=-2.5+0.7 VS 0.8*0 .8mmHg, p=ns). In comparison with G2, only GIFH+ subjects showed a significant decrease in SBP (P=O.03) and DBP @=O.Ot). A negative correlation was found of BP changes with dopamine level (SBP I= -0,135, P=O.024; DBP r -0.119, p=O.047) in FH+ subjects but not in FH- subjects. fn a two-way ANCOVA, FH status cnd urinary dopandne (in a negative fashion, rO.046) were predictive of the weight-related BP fall. Moreover, an FH-dopamin interaction was found on the effect of weight loss (p=O.05). In fact, onfy FH+ low dopamine subjects showed a significant decrease in 24-hour ambtdatoty DBP in comparison with FH+ high dopamine subjects and with FH- groups. fn conclusion weight reduction in mild hypertensive is effective mostly in patients with FH+. Detection of low dopamine values is an additional reason for recommending BW loss in these subjects.
Madrid In INSIGHT a total of 7,428 hypertensive atients with at least one additional risk-factor were,reqmted and 6,5 ! 8 randomized to &ubleb~d@imentwitbci tbermfed,pine once-daily ?rhydmcblorothiczide / amdonde. ,Primary endpoints We mywxdud infarction, stroke, subcracbnold hemorrhage, congestwe heart failure, and sudden dcatb. Rmuitmentstarfed ~ Septembex 1994 andwcs finalized in April 1996. Treatment duration M 3 -4.5 years. Therefore results cre expected in 1999.5 diflerentsde-cnn studies will estabbsbthe relationship between hypertension, progression of atherosclerosis, end organ damage, cnd critical events.
Hm
E Sweden
182
Denmark
133
Norway
71
Total
6588
Key Words:
Proteimtria
2Y0
nifedipine, outcome, hypcrtcnsimt
1
Key worda: hypertension,heredity,obesity,dopamine