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Erectil dysfunction in spanish treated essential hypertensives effects of sildenafil. preliminary report
POSTERS: Clinical Trials
B001
EFFECTS OF WEIGHT REDUCTION, ACE INHIBITOR AND ANGIOTENSIN II ANTAGONIST ON OBESITY HYPERTENSION K. Masuo*, H. Mikami*, T. Ogihara*, M.L. Tuck*. Dept. Geriat. Med., Osaka Univ. Medical School, Osaka, Japan, Sepulveda VA Medical Center, Sepulveda, CA, USA
To clarify the effects of long-term treatments with weight reduction (WR), ACE inhibitor (ACEI; enalapril) and angiotensin II antagonist (AIIA; candesartan) in obese hypertensives on BP reduction, especially focusing on sympathetic activity, renin angiotensin system (RAS), plasma insulin (INS) and leptin (LEP). Five groups with 20 obese hypertensives (HT) each were treated with WR alone, ACEI alone, AIIA alone, ACEI⫹WR, AIIA⫹WR over 12 months. WR was defined as 10% or more reduction in BMI for the first 6 months. The doses of ACEI and AIIA were chosen as less than 140/90 mmHg. At entry, month 6 & 12, BMI, BP, pulse rate (PR), plasma norepinephrine (NE), PRA, AII, INS and LEP were measured after overnight fast. WR program was performed in low caloric diet (1000 kcal, NaCl 7g/day) and exercise. At month 6, WR was succeeded in 65% of WR alone group, 60% of ACEI⫹WR, and 50% of AIIA⫹WR. BP and NE were suppressed in 5 groups at month 6. PRA and AII increased in AIIA alone group, although those decreased in the other 4 groups. At month 6 & 12, BP was lower in order of ACEI⫹WR ⬍ AIIA⫹WR ⬍ ACEI alone ⬍ AIIA alone ⬍ WR. Plasma NE and PR were lower in order of ACEI⫹WR ⬍ ACEI alone ⬍ AIIA⫹WR ⬍ AIIA alone ⬍ WR. AII was lower in order of ACEI⫹WR ⬍ ACEI alone ⬍ WR ⬍ AIIA⫹WR ⬍ AII alone. Plasma INS and LEP were lower in AIIA⫹WR ⬍ ACEI⫹WR ⬍ WR ⬍ AIIA alone ⬍ ACEI alone. In a whole cohort, at month 6 and 12 the reduction in plasma AII (⌬AII) correlated with ⌬NE (P⬍0.01 at month 6, P⬍0.05 at month 12) and ⌬leptin (P⬍0.05 at month 6, P⬍0.05 at month 12). In addition, ⌬insulin correlated with ⌬leptin (P⬍0.05 at month 6, P⬍0.01 at month 12). These results demonstrate that both pharmacological therapies with ACEI & AIIA with WR suppressed sympathetic hyperactivity and activated RAS in obesity hypertension. Despite the fact that BP reduction with WR alone is less than achieved by drugs, weight reduction should be regarded as an essential component of treatment program for obesity hypertension, because of the favorable metabolic responses. Plasma leptin level appears to be regulated by plasma insulin and AII without bradykinin or angiotensin converting enzyme pathways.
Key Words: Angiotensin II antagoniast; ACE inhibitor; weight reduction; obesity; sympathetic activity © 2000 by the American Journal of Hypertension, Ltd. Published by Elsevier Science, Inc.
AJH
2000;13:54A– 67A
B002 TRANDOLAPRIL-VERAPAMIL REDUCES PROTEINURIA IN DIABETIC HYPERTENSIVE PATIENTS INSUFFICIENTLY PRETREATED WITH AN ACE INHIBITOR, AND IN SPITE OF A POOR GLYCEMIC CONTROL A.F. Rubio G.*, C. Trevin˜o G., G. Vargas A., J.L. Narvaez R., J.J. Lozano N., L. Rodriguez L. Hypertension Study Group. dept of Internal Medicine. Ticoman General Hospital SSDF. Mexico D.F. MEXICO We have shown that trandolapril-verapamil (TV) reduces proteinuria in diabetic hypertensive patients (DHP) insufficiently pretreated with an angiotensin converting-enzyme (ACE) inhibitor, even though a group of those patients did not reach an adecuate glycemic control. The aim of this work is to evaluate the effect of TV on proteinuria in a cohort of those DH patients that did not reached a good glycemic control. We include DH patients with blood pressure ⬎ 140/90 mm Hg in spite of more than 6 month of treatment with an ACE inhibitor. They received TV (2/180 mg in the same pill) once a day. In all of them blood pressure was registered monthly (in triplicate), as well as fasting serum glucose. Also 24 hrs proteinuria was determinated at the beggining of the study and six month later, good glycemic control was defined as fasting serum glucose ⬍ 140 mg/dl. Statistical analysis was performed with ANOVA. We found that 30 patients did not reach a good metabolic control during the study, They has a blood pressure reduction from 168⫾5/ 93⫾3 to 135⫾4/79⫾5 mm Hg (p⬍ 0,001). 24 hours proteinuria went down from 4564.7 to 2096.9 mg, (p⬍0.01). three patients suffered symptomatic hypotension and were controlled with half of the dose, we did not find significative changes in heart rate (76⫾6 to 75⫾5 bpm p⬎0.05). We conclude that TV is effective in reducing proteinuria in DH patients insufficiently pretreated with an ACE inhibitor, even in the case of a poor glycemic control, this fact may be relevant in the renoprotection on DH patients. Key Words: Trandolapril/verapamil; proteinuria; diabetes mellitus; renoprotection B003 ERECTIL DYSFUNCTION IN SPANISH TREATED ESSENTIAL HYPERTENSIVES EFFECTS OF SILDENAFIL. PRELIMINARY REPORT P. Aranda(*), L.M. Ruilope(*), A. Coca(*), C. Calvo(*), J. Mora, J. Rodriguez, C. Campos, F.J. Aranda, M. Lo´pez, I. Martinez, M. Luque. Spanish Hypertension Society. Madrid. Spain In a nation-wide survey 367 treated essential hypertensive men (mean time since diagnosis: 8,4⫾4,5 years and mean age: 52,7⫾8 years) were interviewed about their sexual health by filling up the Sexual Health Index for Men (SHIM) form. They had as associated CV risk factors (%): diabetes (35,97); dyslipidemie (27,2) or smoking (11,4), and as CV complications (%) IHD (9,2), Stroke (2.5) or CRF (15). After answering the 5 questions about their sexual activity, the 0895-7061/00/$20.00
AJH–APRIL 2000 –VOL. 13, NO. 4, PART 2
mean score was: 18,3⫾6,3 points, showing 195 (53,1%) a score ⱕ 21 as indicative of erectil dysfunction (ED). The mean duration of HBP was 3,72⫾2,7 years (range: 0,5–15). 76 (39%) patients with ED (mean age: 58,74⫾7,7 years. Mean BMI: 28,4⫾3,2) who had a mean SHIM score of 10.46 ⫾ 5.1 points were treated with Sildenafil. (S). The rest of patients refused or had some contraindications to use S. Associated diseases (%): Diabetes (15,8), Dyslipidemie (9,2), IHD (2,6), Chronic bronchitis (4) and CRF (14,5). Antihypertensive treatment: 25(32,4%) pts were with monoterapie (%): ACEIs: (28), CCBs (24), BBs (12), AB (16), Ds (8) or AIIRAs (12). The rest (67,6%) were treated with two (46,8%) or more drugs. Required dosage of S: 67(88,2%) pts 50 mg, and 9 (11,8%) pts 100 mg. Although 8 (10,5%) pts. were lost during follow-up, 56 (73,7%) pts improved their erectil function. Their International Erectil Function Index (IEFI) improved after S, scoring their global Sexual Satisfaction (from 4,14⫾2 to 6,91⫾2 (p⬍0.000)), their Erectil Function (12,4⫾8 to 20,5⫾8 (p⬍0.000)), their Orgasmic Function (5,01⫾3,7 to 7,2⫾2,7 (p⬍0,000)), as well as their Sexual Appetite (4,68 ⫾ 1,8 to 6,48⫾1,8 (p⬍0.003)). 5 (6,6%) pts showed clinical side-effects (mainly headache), while 10 (13,2%) pts withdrew during follow-up because of lack of efficacy (n⫺3), side-effects (n⫺2) or loss (n⫺5). In conclusion, ED is a quite common disorder among treated hypertensives. S may be usefull in most of them, independently of the n° of antihypertensives taken, improving their sexual function and satisfaction with a good tolerability. Key Words: Erectil dysfunction; arterial hypertension; sildenafil B004 GENDER DIFFERENCES IN THE CLINICAL PROFILE OF COMPLICATED HYPERTENSIVE PATIENTS SEEN IN THE HOSPITAL SETTING P. Aranda-Granados, F.J. Aranda, A. Cansino, P. Aranda(*), Z. Jimenez, E. Lo´pez de Novales. Hypertension Unit. Carlos Haya Hospital. Malaga. Spain Cardiovascular morbidity and mortality rates and causes differ from men to women. Looking at that direction we analyzed the clinical and therapeutic profile of 397 hypertensive patients derived to hospital due to one or more cardiovascular complications. The patients were 223(56,17%) men with a men age mean age 52,8⫾12 years, a mean BP (treated): 162,6⫾22 / 102⫾14 mmHg, HR: 78⫾13 b/min and BMI: 29⫾4.4 kg/m2 compared with 174(43,83) women with a mean age: 52,4⫾13 years, a mean BP: 170⫾30 / 101⫾16 mmHg, HR: 79⫾12, and BMI: 31,3⫾7. Associated C-V risk factors (%) (men vs women): Smoking (35,9/4,6)***; Diabetes (27,8/29,9); Dyslipidemie (44,9/44,3); Obesity (25,1/23). Ethiologic diagnosis (%) (men vs women): Essential HBP: (75,3/70,7); Renal HBP: (13,9/21,3); Renovascular: (6,28/5,75); Hyperaldosteronisms: (2,71/2,3). Cardiovascular complications (%) (men vs women): Stroke ( 20,6/20,7); IHD: (17,9/10,4)*; CHF: (3,6/8,1); CRF: (65,9/56,9). BP control (%) (men vs women): BP ⬍ 140/90: (2,69/8,10); DBP ⬍ 90 mmHg: (18,8/21,8). Use of antihypertensives (%) (men vs women): D: (43,9/37,9); BBs: (31,8/26,4); CCBs: (40,4/ 24,7)***; ACEIs: (55,6/52,3). Use of Statins (%): 7,2 in men
POSTERS: Clinical Trials
55A
and 1,15 in women***. In conclusions, although both group of patients showed a high prevalence of associated CV risk factors and a very poor BP control (even worse in men), men and women with complicated HBP differ because of the higher percentage of smokers among the former and the higher levels of systolic BP and BMI in the later. Theses differences may explain, at least in part, the higher frecuency of IHD, CRF and ischaemic strokes in men while women showed a greater frecuency of CHF and haemorrhagic strokes. (*) p⬍ 0.05; (**) p ⬍ 0.01; (***) p ⬍ 0.001. Key Words: Arterial hypertension; gender; cardiovascular risk
B005 ADMINISTRATION-TIME DEPENDENT EFFECTS OF LOW-DOSE ASPIRIN ON BLOOD PRESSURE IN HIGH RISK PREGNANT WOMEN R.C. Hermida, D.E. Ayala, A. Mojo´n, J.R. Ferna´ndez, M. Iglesias†. Bioengin. & Chronobiol. Labs., Univ. Vigo, Spain; †Hospital Clı´nico Universitario de Santiago, Spain This study extends previous results on the effects of lowdose aspirin on blood pressure (BP) in pregnant women at a higher risk of developing preeclampsia than the general obstetric population who received aspirin at different times of their rest-activity cycle. A double-blind, randomized, placebo-controlled trial was conducted in 274 pregnant women (153 primipara) randomly assigned to 1 of 6 groups according to treatment (placebo or aspirin, 100 mg/d, starting at 12–16 weeks of gestation) and the time of treatment: on awakening (Time-1), 8 hrs after awakening (Time-2), or before bedtime (Time-3). BP for each subject was automatically monitored for 2 days every 4 weeks from the day of recruitment until delivery, as well as at puerperium (6 – 8 weeks after delivery), for a total of 2,048 series. Effects of medication and circadian time of ingestion upon BP along duration of treatment were evaluated by analysis of variance. Results indicated that there was no effect of aspirin on BP at Time-1 (compared with placebo). A BP reduction was, however, highly statistically significant at Time-2 and, to a greater extent, at Time-3 (mean reductions of 13.9 and 9.3 mmHg in 24-hr mean for systolic and diastolic BP, respectively, at the time of delivery as compared to placebo given at the same time). Differences in BP among women receiving ASA at different circadian times disappeared at puerperium (P⬎0.283). Results further indicated a 69% reduction in the incidence of complications (gestational hypertension, preeclampsia, IUGR, and preterm delivery) in the groups receiving aspirin at Time-2 and Time-3, as compared to the other 4 groups where treatment had no effect on BP. Although the mechanism involved in the administration-time dependent responsiveness of BP to aspirin still remains uncertain, the use of doses of aspirin ⬍80 mg/d that do not affect placental thromboxane, initiation of the use of aspirin after 16 weeks’ gestation, and the lack of circadian timing for aspirin administration, could all explain the lack of positive results in previous clinical trials. SUPPORT: PGICT99-PXI-32202B; DGES, PM98-0106; Univ. Vigo.
B001
EFFECTS OF WEIGHT REDUCTION, ACE INHIBITOR AND ANGIOTENSIN II ANTAGONIST ON OBESITY HYPERTENSION K. Masuo*, H. Mikami*, T. Ogihara*, M.L. Tuck*. Dept. Geriat. Med., Osaka Univ. Medical School, Osaka, Japan, Sepulveda VA Medical Center, Sepulveda, CA, USA
To clarify the effects of long-term treatments with weight reduction (WR), ACE inhibitor (ACEI; enalapril) and angiotensin II antagonist (AIIA; candesartan) in obese hypertensives on BP reduction, especially focusing on sympathetic activity, renin angiotensin system (RAS), plasma insulin (INS) and leptin (LEP). Five groups with 20 obese hypertensives (HT) each were treated with WR alone, ACEI alone, AIIA alone, ACEI⫹WR, AIIA⫹WR over 12 months. WR was defined as 10% or more reduction in BMI for the first 6 months. The doses of ACEI and AIIA were chosen as less than 140/90 mmHg. At entry, month 6 & 12, BMI, BP, pulse rate (PR), plasma norepinephrine (NE), PRA, AII, INS and LEP were measured after overnight fast. WR program was performed in low caloric diet (1000 kcal, NaCl 7g/day) and exercise. At month 6, WR was succeeded in 65% of WR alone group, 60% of ACEI⫹WR, and 50% of AIIA⫹WR. BP and NE were suppressed in 5 groups at month 6. PRA and AII increased in AIIA alone group, although those decreased in the other 4 groups. At month 6 & 12, BP was lower in order of ACEI⫹WR ⬍ AIIA⫹WR ⬍ ACEI alone ⬍ AIIA alone ⬍ WR. Plasma NE and PR were lower in order of ACEI⫹WR ⬍ ACEI alone ⬍ AIIA⫹WR ⬍ AIIA alone ⬍ WR. AII was lower in order of ACEI⫹WR ⬍ ACEI alone ⬍ WR ⬍ AIIA⫹WR ⬍ AII alone. Plasma INS and LEP were lower in AIIA⫹WR ⬍ ACEI⫹WR ⬍ WR ⬍ AIIA alone ⬍ ACEI alone. In a whole cohort, at month 6 and 12 the reduction in plasma AII (⌬AII) correlated with ⌬NE (P⬍0.01 at month 6, P⬍0.05 at month 12) and ⌬leptin (P⬍0.05 at month 6, P⬍0.05 at month 12). In addition, ⌬insulin correlated with ⌬leptin (P⬍0.05 at month 6, P⬍0.01 at month 12). These results demonstrate that both pharmacological therapies with ACEI & AIIA with WR suppressed sympathetic hyperactivity and activated RAS in obesity hypertension. Despite the fact that BP reduction with WR alone is less than achieved by drugs, weight reduction should be regarded as an essential component of treatment program for obesity hypertension, because of the favorable metabolic responses. Plasma leptin level appears to be regulated by plasma insulin and AII without bradykinin or angiotensin converting enzyme pathways.
Key Words: Angiotensin II antagoniast; ACE inhibitor; weight reduction; obesity; sympathetic activity © 2000 by the American Journal of Hypertension, Ltd. Published by Elsevier Science, Inc.
AJH
2000;13:54A– 67A
B002 TRANDOLAPRIL-VERAPAMIL REDUCES PROTEINURIA IN DIABETIC HYPERTENSIVE PATIENTS INSUFFICIENTLY PRETREATED WITH AN ACE INHIBITOR, AND IN SPITE OF A POOR GLYCEMIC CONTROL A.F. Rubio G.*, C. Trevin˜o G., G. Vargas A., J.L. Narvaez R., J.J. Lozano N., L. Rodriguez L. Hypertension Study Group. dept of Internal Medicine. Ticoman General Hospital SSDF. Mexico D.F. MEXICO We have shown that trandolapril-verapamil (TV) reduces proteinuria in diabetic hypertensive patients (DHP) insufficiently pretreated with an angiotensin converting-enzyme (ACE) inhibitor, even though a group of those patients did not reach an adecuate glycemic control. The aim of this work is to evaluate the effect of TV on proteinuria in a cohort of those DH patients that did not reached a good glycemic control. We include DH patients with blood pressure ⬎ 140/90 mm Hg in spite of more than 6 month of treatment with an ACE inhibitor. They received TV (2/180 mg in the same pill) once a day. In all of them blood pressure was registered monthly (in triplicate), as well as fasting serum glucose. Also 24 hrs proteinuria was determinated at the beggining of the study and six month later, good glycemic control was defined as fasting serum glucose ⬍ 140 mg/dl. Statistical analysis was performed with ANOVA. We found that 30 patients did not reach a good metabolic control during the study, They has a blood pressure reduction from 168⫾5/ 93⫾3 to 135⫾4/79⫾5 mm Hg (p⬍ 0,001). 24 hours proteinuria went down from 4564.7 to 2096.9 mg, (p⬍0.01). three patients suffered symptomatic hypotension and were controlled with half of the dose, we did not find significative changes in heart rate (76⫾6 to 75⫾5 bpm p⬎0.05). We conclude that TV is effective in reducing proteinuria in DH patients insufficiently pretreated with an ACE inhibitor, even in the case of a poor glycemic control, this fact may be relevant in the renoprotection on DH patients. Key Words: Trandolapril/verapamil; proteinuria; diabetes mellitus; renoprotection B003 ERECTIL DYSFUNCTION IN SPANISH TREATED ESSENTIAL HYPERTENSIVES EFFECTS OF SILDENAFIL. PRELIMINARY REPORT P. Aranda(*), L.M. Ruilope(*), A. Coca(*), C. Calvo(*), J. Mora, J. Rodriguez, C. Campos, F.J. Aranda, M. Lo´pez, I. Martinez, M. Luque. Spanish Hypertension Society. Madrid. Spain In a nation-wide survey 367 treated essential hypertensive men (mean time since diagnosis: 8,4⫾4,5 years and mean age: 52,7⫾8 years) were interviewed about their sexual health by filling up the Sexual Health Index for Men (SHIM) form. They had as associated CV risk factors (%): diabetes (35,97); dyslipidemie (27,2) or smoking (11,4), and as CV complications (%) IHD (9,2), Stroke (2.5) or CRF (15). After answering the 5 questions about their sexual activity, the 0895-7061/00/$20.00
AJH–APRIL 2000 –VOL. 13, NO. 4, PART 2
mean score was: 18,3⫾6,3 points, showing 195 (53,1%) a score ⱕ 21 as indicative of erectil dysfunction (ED). The mean duration of HBP was 3,72⫾2,7 years (range: 0,5–15). 76 (39%) patients with ED (mean age: 58,74⫾7,7 years. Mean BMI: 28,4⫾3,2) who had a mean SHIM score of 10.46 ⫾ 5.1 points were treated with Sildenafil. (S). The rest of patients refused or had some contraindications to use S. Associated diseases (%): Diabetes (15,8), Dyslipidemie (9,2), IHD (2,6), Chronic bronchitis (4) and CRF (14,5). Antihypertensive treatment: 25(32,4%) pts were with monoterapie (%): ACEIs: (28), CCBs (24), BBs (12), AB (16), Ds (8) or AIIRAs (12). The rest (67,6%) were treated with two (46,8%) or more drugs. Required dosage of S: 67(88,2%) pts 50 mg, and 9 (11,8%) pts 100 mg. Although 8 (10,5%) pts. were lost during follow-up, 56 (73,7%) pts improved their erectil function. Their International Erectil Function Index (IEFI) improved after S, scoring their global Sexual Satisfaction (from 4,14⫾2 to 6,91⫾2 (p⬍0.000)), their Erectil Function (12,4⫾8 to 20,5⫾8 (p⬍0.000)), their Orgasmic Function (5,01⫾3,7 to 7,2⫾2,7 (p⬍0,000)), as well as their Sexual Appetite (4,68 ⫾ 1,8 to 6,48⫾1,8 (p⬍0.003)). 5 (6,6%) pts showed clinical side-effects (mainly headache), while 10 (13,2%) pts withdrew during follow-up because of lack of efficacy (n⫺3), side-effects (n⫺2) or loss (n⫺5). In conclusion, ED is a quite common disorder among treated hypertensives. S may be usefull in most of them, independently of the n° of antihypertensives taken, improving their sexual function and satisfaction with a good tolerability. Key Words: Erectil dysfunction; arterial hypertension; sildenafil B004 GENDER DIFFERENCES IN THE CLINICAL PROFILE OF COMPLICATED HYPERTENSIVE PATIENTS SEEN IN THE HOSPITAL SETTING P. Aranda-Granados, F.J. Aranda, A. Cansino, P. Aranda(*), Z. Jimenez, E. Lo´pez de Novales. Hypertension Unit. Carlos Haya Hospital. Malaga. Spain Cardiovascular morbidity and mortality rates and causes differ from men to women. Looking at that direction we analyzed the clinical and therapeutic profile of 397 hypertensive patients derived to hospital due to one or more cardiovascular complications. The patients were 223(56,17%) men with a men age mean age 52,8⫾12 years, a mean BP (treated): 162,6⫾22 / 102⫾14 mmHg, HR: 78⫾13 b/min and BMI: 29⫾4.4 kg/m2 compared with 174(43,83) women with a mean age: 52,4⫾13 years, a mean BP: 170⫾30 / 101⫾16 mmHg, HR: 79⫾12, and BMI: 31,3⫾7. Associated C-V risk factors (%) (men vs women): Smoking (35,9/4,6)***; Diabetes (27,8/29,9); Dyslipidemie (44,9/44,3); Obesity (25,1/23). Ethiologic diagnosis (%) (men vs women): Essential HBP: (75,3/70,7); Renal HBP: (13,9/21,3); Renovascular: (6,28/5,75); Hyperaldosteronisms: (2,71/2,3). Cardiovascular complications (%) (men vs women): Stroke ( 20,6/20,7); IHD: (17,9/10,4)*; CHF: (3,6/8,1); CRF: (65,9/56,9). BP control (%) (men vs women): BP ⬍ 140/90: (2,69/8,10); DBP ⬍ 90 mmHg: (18,8/21,8). Use of antihypertensives (%) (men vs women): D: (43,9/37,9); BBs: (31,8/26,4); CCBs: (40,4/ 24,7)***; ACEIs: (55,6/52,3). Use of Statins (%): 7,2 in men
POSTERS: Clinical Trials
55A
and 1,15 in women***. In conclusions, although both group of patients showed a high prevalence of associated CV risk factors and a very poor BP control (even worse in men), men and women with complicated HBP differ because of the higher percentage of smokers among the former and the higher levels of systolic BP and BMI in the later. Theses differences may explain, at least in part, the higher frecuency of IHD, CRF and ischaemic strokes in men while women showed a greater frecuency of CHF and haemorrhagic strokes. (*) p⬍ 0.05; (**) p ⬍ 0.01; (***) p ⬍ 0.001. Key Words: Arterial hypertension; gender; cardiovascular risk
B005 ADMINISTRATION-TIME DEPENDENT EFFECTS OF LOW-DOSE ASPIRIN ON BLOOD PRESSURE IN HIGH RISK PREGNANT WOMEN R.C. Hermida, D.E. Ayala, A. Mojo´n, J.R. Ferna´ndez, M. Iglesias†. Bioengin. & Chronobiol. Labs., Univ. Vigo, Spain; †Hospital Clı´nico Universitario de Santiago, Spain This study extends previous results on the effects of lowdose aspirin on blood pressure (BP) in pregnant women at a higher risk of developing preeclampsia than the general obstetric population who received aspirin at different times of their rest-activity cycle. A double-blind, randomized, placebo-controlled trial was conducted in 274 pregnant women (153 primipara) randomly assigned to 1 of 6 groups according to treatment (placebo or aspirin, 100 mg/d, starting at 12–16 weeks of gestation) and the time of treatment: on awakening (Time-1), 8 hrs after awakening (Time-2), or before bedtime (Time-3). BP for each subject was automatically monitored for 2 days every 4 weeks from the day of recruitment until delivery, as well as at puerperium (6 – 8 weeks after delivery), for a total of 2,048 series. Effects of medication and circadian time of ingestion upon BP along duration of treatment were evaluated by analysis of variance. Results indicated that there was no effect of aspirin on BP at Time-1 (compared with placebo). A BP reduction was, however, highly statistically significant at Time-2 and, to a greater extent, at Time-3 (mean reductions of 13.9 and 9.3 mmHg in 24-hr mean for systolic and diastolic BP, respectively, at the time of delivery as compared to placebo given at the same time). Differences in BP among women receiving ASA at different circadian times disappeared at puerperium (P⬎0.283). Results further indicated a 69% reduction in the incidence of complications (gestational hypertension, preeclampsia, IUGR, and preterm delivery) in the groups receiving aspirin at Time-2 and Time-3, as compared to the other 4 groups where treatment had no effect on BP. Although the mechanism involved in the administration-time dependent responsiveness of BP to aspirin still remains uncertain, the use of doses of aspirin ⬍80 mg/d that do not affect placental thromboxane, initiation of the use of aspirin after 16 weeks’ gestation, and the lack of circadian timing for aspirin administration, could all explain the lack of positive results in previous clinical trials. SUPPORT: PGICT99-PXI-32202B; DGES, PM98-0106; Univ. Vigo.