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P130 Compliance with HRT in postmenopausal women with coronary artery disease
P130
Pl31
COMPL~NCE WITH HRT IN POSTMENOPAUSAL WOMEN WITH CORONARY ARTERY DISEASE. G Hall, U Pripp, K Schenck-Gustafsson,
URINARY SU~OGATE-MARKERS FOR VASCULAR EFFECTS OF TRANSDERMAL AND ORAL ESTRADIOL IN, POSTMENOPAUSAL WOMEN
B-M Landgren,
Dept of Ob. and Gyn. and Dept of Cardiology,KarolinskaInstitute andHospital,S-17176 Stockholm,Sweden 61 womenwith documentedcoronaryartery disease, meanage595 years+ 67 wererandomised into threetreatmentregiments: 1) TTSE2(50 ug/24 hours)for 18 daysfollowed by TTSEz+ MPA (5 mg)for 10days(n=20). 2) (TTSE2+ MPA) -placebo(n=21). 3) Conjugatedestrogen(CE) (0,625mgdaily) + MPA 5 mg(n=20). The womenwerefollowedfor oneyear. 46 completedthe study, 14 in both TTS groupsand 18 in the CE estrogengroup. 15 women droppedout. One death - myocardial infarction (placebo),one colectomy (TTSE,), two TIA (TTSE*), two heavy bleedings (TTSE& one severeheadache(CE) and one allergic skin reaction (TTSE2),onepalpitations(CE), five failuresto cooperate(placebo), and one periferai edema(placebo). No differencesin negative adverseeventswerefound betweenthosewho completedthe study and the drop-outs. The women who completedthe study experienced significantlymorewell-beingthanthe drop-outs. 42 continuedHRT after the studyyear, 12from the TTSEzgroup, 13 from the placebogroup,and 17from the CE group. Conclusion: It seemsthat the positive effect of treatmentis moreimpo~antfor compliancethanadverseeffectsin olderwomenwith coronaryartery disease.
P132
TH Liuuert, H Seeger, A0 Mueck
University Hospital,Dept. OB/GYN, Clinical Pharmacology72076 Tuebingen,Germany Vasodilationtriggeredby estradioi(E2) may be mediatedby various vasoactivesubstances. The aimof the presentstudywasto investigate theinfluenceof transdennal andoralE2 on biochemical markerswhich can reflect the productionof vasoactivesubstances.Method: 40 postmenopausal womenwith climactericsymptoms receivedfor 4 weeks unoppo~ estradiol,i.e.20womentransdermal E2 (0.05mgidie)and20 womenoralE2 (2 mgidie).Nocturnalurine- excretedbetween10 pm and 6 am - was collectedbefore,after 14and28 daysof treatment.The following surrogate-markers were determinedin the urine by radioimmunoassays: prostacyclin-metabolites, thromboxane-metabohtes, cGMP (reflectingNO production);serotonin-metabolite; relaxin and insulin. Results:Pros~ycli~ ~ombox~~mtio was si~ifi~tIy increased aftertransdermal aswell asoralE2. cGMP excretionshowed only a tendencyto increase with transdermal E2. Serotonin-metabolite wassignificantlyincreased after oral and transdermal E2, relaxinand insulinweresignificantlyenhanced only aftertransdermal E2 treatment. Conclusions: Themeasurement of vasoactivesubstances, excretedin the urine, may reflect the mechanismby which estradiolproduces v~il~ion. Theinc~mentof pro~ycli~ ~o~x~e-mtio indicates a vasodilativeeffect of tmnsdermalas well as oral E2 involving eicosanoids. Thesignificance of urinarycGMPreflectingNO production remains unclear.The increase of the vasoactivesubstances serotonin relaxinandinsulinin the urinehasto besubjectto further studies.
P132 (cant)
COADMINISTRATION OF MOEXIPRIL AND HORMONAL REPLACEMENT THERAPY IN POSTMENOPAUSAL WOMEN Moexiprit waswell-toleratedamongpostmenopausal womenusing HRT. The mostfrequently occurringadverseevents for moexiprit for the investigatorsof the MADAM programme(Moexipril as includedheadache (21.3%),cough( 12.8%)andrhinitis ( 10.6%)and Antihypertensive Drug After Menopause), Dept. of Clinical there were no significant differencesin the numberand severity of Research, SchwarzPharma,Monheim,Germany adverseeventsbetweenthemoexiprilandplacebogroups. Coadminis~ationof antihypertensivedrug therapy and ho~ona1 This study indicatesthat moexipri! is effective and well toleratedin the Trident of hype~ensive,po~enopaus~ women and can replacementtherapy (HRT) may be required in pos~enopausal safelybecoadministered to HRT. women. Sinceno data is availableon whetherHR’T interactswith concomitanttherapy, the presentstudy wasoutlinedto investigate efficacy and safetyof the ACE inhibitor moexiprilin comparisonto placeboin hypertensive,postmenopausal womenon HRT. After a 4-weekplaceborun-mphase95 postmenopausal women(3574 years of age) were randomizedto a IZweek treatmentwith moexipril 15 mg or placebowhen having a sitting diastolicblood pressure(BP) of 95-114 mmHg and being treated with HRT. Efficacy andsafetywasassessed by measuring changes in sittingblood pressure and selected metabolic parametersassociatedwith cardiovascular disease andby continuouslyrecordingadverseevents. After 12weeksof treatmentmoexipril 15mg wassi~ifi~tiy more effective in reducingsitting systolicand diastolicBP from baseline than placebo (-12.21-9.9mmHg vs. -1.614.3mmHg, p
(-33.6%).
Continued 157
Pl31
COMPL~NCE WITH HRT IN POSTMENOPAUSAL WOMEN WITH CORONARY ARTERY DISEASE. G Hall, U Pripp, K Schenck-Gustafsson,
URINARY SU~OGATE-MARKERS FOR VASCULAR EFFECTS OF TRANSDERMAL AND ORAL ESTRADIOL IN, POSTMENOPAUSAL WOMEN
B-M Landgren,
Dept of Ob. and Gyn. and Dept of Cardiology,KarolinskaInstitute andHospital,S-17176 Stockholm,Sweden 61 womenwith documentedcoronaryartery disease, meanage595 years+ 67 wererandomised into threetreatmentregiments: 1) TTSE2(50 ug/24 hours)for 18 daysfollowed by TTSEz+ MPA (5 mg)for 10days(n=20). 2) (TTSE2+ MPA) -placebo(n=21). 3) Conjugatedestrogen(CE) (0,625mgdaily) + MPA 5 mg(n=20). The womenwerefollowedfor oneyear. 46 completedthe study, 14 in both TTS groupsand 18 in the CE estrogengroup. 15 women droppedout. One death - myocardial infarction (placebo),one colectomy (TTSE,), two TIA (TTSE*), two heavy bleedings (TTSE& one severeheadache(CE) and one allergic skin reaction (TTSE2),onepalpitations(CE), five failuresto cooperate(placebo), and one periferai edema(placebo). No differencesin negative adverseeventswerefound betweenthosewho completedthe study and the drop-outs. The women who completedthe study experienced significantlymorewell-beingthanthe drop-outs. 42 continuedHRT after the studyyear, 12from the TTSEzgroup, 13 from the placebogroup,and 17from the CE group. Conclusion: It seemsthat the positive effect of treatmentis moreimpo~antfor compliancethanadverseeffectsin olderwomenwith coronaryartery disease.
P132
TH Liuuert, H Seeger, A0 Mueck
University Hospital,Dept. OB/GYN, Clinical Pharmacology72076 Tuebingen,Germany Vasodilationtriggeredby estradioi(E2) may be mediatedby various vasoactivesubstances. The aimof the presentstudywasto investigate theinfluenceof transdennal andoralE2 on biochemical markerswhich can reflect the productionof vasoactivesubstances.Method: 40 postmenopausal womenwith climactericsymptoms receivedfor 4 weeks unoppo~ estradiol,i.e.20womentransdermal E2 (0.05mgidie)and20 womenoralE2 (2 mgidie).Nocturnalurine- excretedbetween10 pm and 6 am - was collectedbefore,after 14and28 daysof treatment.The following surrogate-markers were determinedin the urine by radioimmunoassays: prostacyclin-metabolites, thromboxane-metabohtes, cGMP (reflectingNO production);serotonin-metabolite; relaxin and insulin. Results:Pros~ycli~ ~ombox~~mtio was si~ifi~tIy increased aftertransdermal aswell asoralE2. cGMP excretionshowed only a tendencyto increase with transdermal E2. Serotonin-metabolite wassignificantlyincreased after oral and transdermal E2, relaxinand insulinweresignificantlyenhanced only aftertransdermal E2 treatment. Conclusions: Themeasurement of vasoactivesubstances, excretedin the urine, may reflect the mechanismby which estradiolproduces v~il~ion. Theinc~mentof pro~ycli~ ~o~x~e-mtio indicates a vasodilativeeffect of tmnsdermalas well as oral E2 involving eicosanoids. Thesignificance of urinarycGMPreflectingNO production remains unclear.The increase of the vasoactivesubstances serotonin relaxinandinsulinin the urinehasto besubjectto further studies.
P132 (cant)
COADMINISTRATION OF MOEXIPRIL AND HORMONAL REPLACEMENT THERAPY IN POSTMENOPAUSAL WOMEN Moexiprit waswell-toleratedamongpostmenopausal womenusing HRT. The mostfrequently occurringadverseevents for moexiprit for the investigatorsof the MADAM programme(Moexipril as includedheadache (21.3%),cough( 12.8%)andrhinitis ( 10.6%)and Antihypertensive Drug After Menopause), Dept. of Clinical there were no significant differencesin the numberand severity of Research, SchwarzPharma,Monheim,Germany adverseeventsbetweenthemoexiprilandplacebogroups. Coadminis~ationof antihypertensivedrug therapy and ho~ona1 This study indicatesthat moexipri! is effective and well toleratedin the Trident of hype~ensive,po~enopaus~ women and can replacementtherapy (HRT) may be required in pos~enopausal safelybecoadministered to HRT. women. Sinceno data is availableon whetherHR’T interactswith concomitanttherapy, the presentstudy wasoutlinedto investigate efficacy and safetyof the ACE inhibitor moexiprilin comparisonto placeboin hypertensive,postmenopausal womenon HRT. After a 4-weekplaceborun-mphase95 postmenopausal women(3574 years of age) were randomizedto a IZweek treatmentwith moexipril 15 mg or placebowhen having a sitting diastolicblood pressure(BP) of 95-114 mmHg and being treated with HRT. Efficacy andsafetywasassessed by measuring changes in sittingblood pressure and selected metabolic parametersassociatedwith cardiovascular disease andby continuouslyrecordingadverseevents. After 12weeksof treatmentmoexipril 15mg wassi~ifi~tiy more effective in reducingsitting systolicand diastolicBP from baseline than placebo (-12.21-9.9mmHg vs. -1.614.3mmHg, p
(-33.6%).
Continued 157