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Lifestyle changes
AJH-APRIL 1997-VOL. 10, NO. 4, PART 2
ASH XII ABSTRACTS
WednesdayMay 28, BallroomB, 8:30 am New PharmacologicApproachesto the Managementof Hypertension
M.D. Professor of kedicine, Indiana University School of Medicine, Indianapolis, Indiana
ClinicalOverviewofrrlwmrtan: A New AIIReceptorAntagonist H. Pouleur,M.D., Ph.D. frbesartanis a potentandspecificantagonistof AT,receptors,witha much greatoraftinity(morethan8500-fold)fortheAT,receptorthanfortheATZ mc.?Ptor.frbesartanexhibitslinearphannacoti,neticsoverrhotherapeutic dosenmgswithatennittaleliminationhalf-lifeofirbssartanaveraging1115 hours. No gender related differencesin phanmacokineticswere ohservedin healthyelderlyor in healthyyoungsubjects. No dosage adju.stmentis necessaryinpatientswithrenalimptintor inpatientswith mild to mcderat.?cirrhosisof the liver. Inhealthysubjects,singleoral irhssartandosos of up to 3C0mg produceddose-dependentinhibition &90% at peak) of the presser effect of angiotensin11infusions,and sustainedfor24 hours(60%at 30+Jmg). The antihypertensive effectsof irbesartanwereexaminedin 7 majorplacebo-controlled 8-12weaktrials inpatientswithbaselinediastolicblocdpressuresof95-llOmmHg. Doses ware included hthese trialsinorderto fullyexplorethe doseof l-900mg rangeof irbesartamThe 7 studiesof irbesartanmonotherapyincludeda totalof 1915patiermrandomizedto irbesartan(1-900mg)and611patients randomizedto placebo.Once daily doses of 150 to 900 mg provided statisticallyand clinicallysignificantdecreasesin systolicand diastolic blood pressure with a plateau effect at doses above 300 mg. (24hours Systolicldiastolicmeandecreasesin bloodpressureat trough post-dosing), compared toplacebo, follo~ng 6 to12wee~ ofneatment werein the rangeof 7.5-9 .9/4.6-6.2 nunlfg whha 150mg dose, and7.912.6/5 .2-7.9 mmHg wiha300mg dose. Oncedailydosingwith 150mg irbesartanand 12.5mg hydrochlomthiazide gavesystolic/diastolicmean placebo-acjustedblood pressurereductionsat trough (24 hours postdosing)of 14.6-18.0/8.4-9.6mmHg. Irb-e.sartan hasbaenevaluated for safety in more than 43(XIpatients with hypertensionand about 5000 subjectsoverall. Treatmentwith irhesartanwas well-toleratedwith an incidenceof adverseeventssimilarto placebo. Theseeventsgenerally weremildandtransientwithno relationshipto the doseof irbesartan.In placebo-controlledclinical trials, discontinuationof therapydue to a clinicaladverseeventwasrequiredin 3.3percentof patientstreatedwith irbesartan,versus4.5 percentof patientsgivenplacebo. KeyWords:
Elevatedblood pressure results from a variety of abnormalities including genetic factors,environmentalcomponents and acquired abnormalities.Many of these aspects of lifestyle have been found to play a role in the development or maintenanceof hypertension.Such factors include increased body weight (generally resulting from increasedcaloric intake), decreasedexercise,increasedconsumption of alcohol and salt or decreased intake of potassium and calcium. While these may not consistentlybe involved in the blood pressure elevation of all hypertensives, attention to the lifestyle factors may lower blood pressure in many patients. Moreover, such lifestyle changes, if maintained, can reduce the amount of medication reguired for optimal blood pressure control. Finally, in susceptible individua 1s, institution lifestyle measures holds for primary prevention of
of
sDeci
f ic
the potential hypertension.
Irbesartan,Hypertension,AngiotensinII
WednesdayMay 28, BallroomA, 8:30 am Two Dialogueson TreatingHypertension Selecting Antihypetiensive Therapy: Pickingthe First Choice. HenryR. Black,M.D. Rush-Presbyterfan-St. Luke’sMadicalCenter Departmentof PreventiveMadlcine Chisago,Illinois The mostimportanttherapeuticdecisionmadewhentreatingthe hypeiiensivepatientis the selectionof initial therapy. Though4050°/0of patientscurrentlyremainontheir first dmg prescribed,I feel that this percentagewouldincreasedramaticallyif we usethe initial evaluationto guideour choiceand if we are clear aato howcertain subgroupsof patientsrespondto antihyperiensivetherapy. All antihyperlensivesare at leastsomewhateffective in all sukgroups of patients,aosimply uaingdemographyas a guideto a choiesof therapy,is only modestlyhelpful. It is true, for example, that older African-Americanstend to respondbetterto calciumentryblockers and lesswell to beta-blockersand ACE Inhibitors,manywill do well withtheseagents. YoungerAfricanAmericando almostas well withACE Inhibitorsas they do with otherdregsexceptpetiraps calciumentryblockem,wherethe responserate is higher. The responseratesin whitesof all agesare similarwith all classesof dregs. The mostimpotiantfactor in makingthe initial selectionis comorbidity. Patientswho havecertainconditions,suchas congestiveheari failure or anginabenefitfrom drugswhichwould treat bothof thesaproblema. Patientswith other conditions,euch as asthmashouldnot receivebeta-blockersand patientawith gout shouldnot receivethiazidediuretics. It is unclearhowmuchthe metabolicchangesassociatedwith diureticsand beta-blockers affect patientswith hyperlipidemiaor glucoseintolerancebut these conditionsshouldbetaken into considerationwhen makinga choice. Finally,abilityto pay is an importantconsiderationsince patientsmustbe ableto purchaseantihypetfensivetherapyif we expectthem to betreated. KeyWords:
WednesdayMay 28, BallroomA, 8:30 am Two Dialogueson TreatingHypertension LIFEsTym CHANGES Myron H. Weinberger,
Antihypertensive;individualization
—.
WednesdayMay 28, BallroomC, 12:00 pm AchievingComprehensiveHypertension Managem-ent HOW TO DEVELOPA PIXED-DOSE COMBINATION Nonnan M. Kaplan, M.D., University of Texas Southwestern Medical Center, Dallaa, Texas Fixeddoeecombinations are rapidly beingreintroduced, somees irsitkd therapy formifd-moderate hypertension, others asneceasery forsnszirnal protection against renal andcardiac rnartifestadone. Unfifre those available inthepaat, thenewerforrnulationa arebasedon a numberofprinciples, istehtding: - use of the lowest doses poaaible, particularly if a diuretic is one of the ingredients usc of agents which maximize antihypertenaive efficacy use of agenta which minimize the potential for adverse effeete - use of agenta which act aynergiaticallyto overcome multiple medtaniams that raise blood presaure or aeeeleretetarget organ darnage Examples will be given of a variety of fmed-doac combimtions that are currently marketed or in the last stages of development with a critical aaeeaamentof how they meet the above principles.
ASH XII ABSTRACTS
WednesdayMay 28, BallroomB, 8:30 am New PharmacologicApproachesto the Managementof Hypertension
M.D. Professor of kedicine, Indiana University School of Medicine, Indianapolis, Indiana
ClinicalOverviewofrrlwmrtan: A New AIIReceptorAntagonist H. Pouleur,M.D., Ph.D. frbesartanis a potentandspecificantagonistof AT,receptors,witha much greatoraftinity(morethan8500-fold)fortheAT,receptorthanfortheATZ mc.?Ptor.frbesartanexhibitslinearphannacoti,neticsoverrhotherapeutic dosenmgswithatennittaleliminationhalf-lifeofirbssartanaveraging1115 hours. No gender related differencesin phanmacokineticswere ohservedin healthyelderlyor in healthyyoungsubjects. No dosage adju.stmentis necessaryinpatientswithrenalimptintor inpatientswith mild to mcderat.?cirrhosisof the liver. Inhealthysubjects,singleoral irhssartandosos of up to 3C0mg produceddose-dependentinhibition &90% at peak) of the presser effect of angiotensin11infusions,and sustainedfor24 hours(60%at 30+Jmg). The antihypertensive effectsof irbesartanwereexaminedin 7 majorplacebo-controlled 8-12weaktrials inpatientswithbaselinediastolicblocdpressuresof95-llOmmHg. Doses ware included hthese trialsinorderto fullyexplorethe doseof l-900mg rangeof irbesartamThe 7 studiesof irbesartanmonotherapyincludeda totalof 1915patiermrandomizedto irbesartan(1-900mg)and611patients randomizedto placebo.Once daily doses of 150 to 900 mg provided statisticallyand clinicallysignificantdecreasesin systolicand diastolic blood pressure with a plateau effect at doses above 300 mg. (24hours Systolicldiastolicmeandecreasesin bloodpressureat trough post-dosing), compared toplacebo, follo~ng 6 to12wee~ ofneatment werein the rangeof 7.5-9 .9/4.6-6.2 nunlfg whha 150mg dose, and7.912.6/5 .2-7.9 mmHg wiha300mg dose. Oncedailydosingwith 150mg irbesartanand 12.5mg hydrochlomthiazide gavesystolic/diastolicmean placebo-acjustedblood pressurereductionsat trough (24 hours postdosing)of 14.6-18.0/8.4-9.6mmHg. Irb-e.sartan hasbaenevaluated for safety in more than 43(XIpatients with hypertensionand about 5000 subjectsoverall. Treatmentwith irhesartanwas well-toleratedwith an incidenceof adverseeventssimilarto placebo. Theseeventsgenerally weremildandtransientwithno relationshipto the doseof irbesartan.In placebo-controlledclinical trials, discontinuationof therapydue to a clinicaladverseeventwasrequiredin 3.3percentof patientstreatedwith irbesartan,versus4.5 percentof patientsgivenplacebo. KeyWords:
Elevatedblood pressure results from a variety of abnormalities including genetic factors,environmentalcomponents and acquired abnormalities.Many of these aspects of lifestyle have been found to play a role in the development or maintenanceof hypertension.Such factors include increased body weight (generally resulting from increasedcaloric intake), decreasedexercise,increasedconsumption of alcohol and salt or decreased intake of potassium and calcium. While these may not consistentlybe involved in the blood pressure elevation of all hypertensives, attention to the lifestyle factors may lower blood pressure in many patients. Moreover, such lifestyle changes, if maintained, can reduce the amount of medication reguired for optimal blood pressure control. Finally, in susceptible individua 1s, institution lifestyle measures holds for primary prevention of
of
sDeci
f ic
the potential hypertension.
Irbesartan,Hypertension,AngiotensinII
WednesdayMay 28, BallroomA, 8:30 am Two Dialogueson TreatingHypertension Selecting Antihypetiensive Therapy: Pickingthe First Choice. HenryR. Black,M.D. Rush-Presbyterfan-St. Luke’sMadicalCenter Departmentof PreventiveMadlcine Chisago,Illinois The mostimportanttherapeuticdecisionmadewhentreatingthe hypeiiensivepatientis the selectionof initial therapy. Though4050°/0of patientscurrentlyremainontheir first dmg prescribed,I feel that this percentagewouldincreasedramaticallyif we usethe initial evaluationto guideour choiceand if we are clear aato howcertain subgroupsof patientsrespondto antihyperiensivetherapy. All antihyperlensivesare at leastsomewhateffective in all sukgroups of patients,aosimply uaingdemographyas a guideto a choiesof therapy,is only modestlyhelpful. It is true, for example, that older African-Americanstend to respondbetterto calciumentryblockers and lesswell to beta-blockersand ACE Inhibitors,manywill do well withtheseagents. YoungerAfricanAmericando almostas well withACE Inhibitorsas they do with otherdregsexceptpetiraps calciumentryblockem,wherethe responserate is higher. The responseratesin whitesof all agesare similarwith all classesof dregs. The mostimpotiantfactor in makingthe initial selectionis comorbidity. Patientswho havecertainconditions,suchas congestiveheari failure or anginabenefitfrom drugswhichwould treat bothof thesaproblema. Patientswith other conditions,euch as asthmashouldnot receivebeta-blockersand patientawith gout shouldnot receivethiazidediuretics. It is unclearhowmuchthe metabolicchangesassociatedwith diureticsand beta-blockers affect patientswith hyperlipidemiaor glucoseintolerancebut these conditionsshouldbetaken into considerationwhen makinga choice. Finally,abilityto pay is an importantconsiderationsince patientsmustbe ableto purchaseantihypetfensivetherapyif we expectthem to betreated. KeyWords:
WednesdayMay 28, BallroomA, 8:30 am Two Dialogueson TreatingHypertension LIFEsTym CHANGES Myron H. Weinberger,
Antihypertensive;individualization
—.
WednesdayMay 28, BallroomC, 12:00 pm AchievingComprehensiveHypertension Managem-ent HOW TO DEVELOPA PIXED-DOSE COMBINATION Nonnan M. Kaplan, M.D., University of Texas Southwestern Medical Center, Dallaa, Texas Fixeddoeecombinations are rapidly beingreintroduced, somees irsitkd therapy formifd-moderate hypertension, others asneceasery forsnszirnal protection against renal andcardiac rnartifestadone. Unfifre those available inthepaat, thenewerforrnulationa arebasedon a numberofprinciples, istehtding: - use of the lowest doses poaaible, particularly if a diuretic is one of the ingredients usc of agents which maximize antihypertenaive efficacy use of agenta which minimize the potential for adverse effeete - use of agenta which act aynergiaticallyto overcome multiple medtaniams that raise blood presaure or aeeeleretetarget organ darnage Examples will be given of a variety of fmed-doac combimtions that are currently marketed or in the last stages of development with a critical aaeeaamentof how they meet the above principles.