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The antiproteinuric effect of enalapril is potentiated by losartan in normotensive patients with diabetic nephropathy
AJH–APRIL 2000 –VOL. 13, NO. 4, PART 2
Blood pressure reduction, effect duration and tolerability of the AT1-receptor blocker candesartan and the ACE inhibitor enalapril, once daily, was studied in a multicenter, doubleblind, randomised, parallel group study. A total of 395 patients, aged 20 – 80 years, with mean sitting diastolic blood pressure 95–114 mmHg and mean awake diastolic ambulatory blood pressure (ABP) ⬎85 mmHg after a 4-week placebo run-in period were randomised to 8 weeks treatment. The starting doses were candesartan cilexetil 8 mg or enalapril 10 mg. After 4 weeks the doses were doubled to 16 mg and 20 mg respectively, for all patients. At the end of the study, ABP was measured 0 –36 hours after dose. Trough blood pressure was calculated as ABP 22–24 hours post dose. The mean adjusted reduction from baseline to after 8 weeks of trough diastolic ABP was 8.7 mmHg (95% CI 7.0 –10.5) in the candesartan group vs 5.8 mmHg (95% CI 4.0 –7.6) in the enalapril group (p ⫽ 0.008). For trough systolic ABP 22–24 hours post dose, the mean adjusted reduction in the candesartan group was 13.5 mmHg (95% CI 10.9 –16.1) vs 9.9 mmHg (95% CI 7.3–12.6) in the enalapril group (p ⫽ 0.032). Mean adjusted reduction of diastolic ABP on the day of a missed dose (6 a.m.– 6 p.m.) was 8.0 mmHg (95% CI 6.7–9.3) in the candesartan group vs 4.5 mmHg (95% CI 3.2–5.9) in the enalapril group (p ⬍ 0.001). The corresponding reductions in systolic ABP were 11.4 mmHg (95% CI 9.3–13.5) with candesartan and 7.2 mmHg (95% CI 5.1– 9.4) with enalapril (p ⫽ 0.002). The proportion of patients who discontinued due to adverse events was 2.0% and 3.6% in the candesartan and enalapril groups, respectively. Once-daily candesartan cilexetil, 16 mg, was superior to enalapril, 20 mg, in reducing blood pressure at trough. At least 12 hours after a missed dose there was a persistent reduction of blood pressure during treatment with candesartan. Both treatments were well tolerated. Key Words: Candesartan; cilexetil; enalapril; ambulatory blood pressure; missed dose A017 THE ANTIPROTEINURIC EFFECT OF ENALAPRIL IS POTENTIATED BY LOSARTAN IN NORMOTENSIVE PATIENTS WITH DIABETIC NEPHROPATHY J. Arteaga*, E. Petrina, E. Anda, D. Calderon, M. Sorbet, M. Asiro´n. Dept. of Nephrology. Hospital de Navarra. Pamplona. Spain It is well known that enalapril and losartan play an important role in decreasing proteinuria in diabetic nephropathy. The aim of this work was to analyze if the addition of losartan 50 mg/day to normotensive diabetic patients with normal renal function in treatment with enalapril could be beneficial in terms of decreasing proteinuria. We selected 10 patients (4M, 6F) with type 2 diabetes, normotensives, proteinuric and with normal renal function in treatment with enalapril 10 –20 mg/day (6 –14 months). We added Losartan 50 mg/day for two months and then, enalapril was discontinued for another two months. They were their own control. There were no significant changes in weight, serum creatinine, sistolic and diastolic blood pressure.
POSTERS: Antihypertensive Drugs
Enalapril Proteinuria gr/24 h (Paired t-test)
117A
enalapril ⴙ losartan
Losartan
1,955 ⫾ 0,334
2,458 ⫾ 0,428
2,396 ⫾ 0,535 p ⬍ 0,05
p ⬍ 0,01
A decrease in proteinuric levels was observed during the combination time period. After stopping enalapril there was an increase of proteinuria that reached similar levels to the first period ones. We suggest that the additive effect of enalapril and losartan could be an elective treatment in patients with diabetic nephropathy. Long term studies are necessary to confirm the useful effect of this association. Key Words: Diabetic nephropathy; enalapril; losartan hypertension
A018 CONTROL OF BLOOD PRESSURE IN A POPULATION OF WOMEN WITH HYPERTENSION AND CAD USING AN INTERNET-BASED ELECTRONIC PRESCRIBING SYSTEM R.M. Cooper-DeHoff, E.M. Handberg-Thurmond, R.G. Marks, M. Conlon, H.R. Kolb, C.J. Pepine for the INVEST Investigators. University of Florida, Gainesville, FL Background: Adequate BP control in patients with hypertension is difficult as various reports document that only 16 –24% of patients actually achieve control despite treatment. Because coronary artery disease (CAD) is the #1 killer of women, it is imperative that focus be placed on adequate BP control in women who are hypertensive and have CAD. Data for CAD & women are lacking. To determine what is required to control BP using JNC VI criteria with lower targets for special populations, we examined data from a cohort of women with CAD enrolled in an ongoing trial. Methods: The INternational VErapamil/trandolapril Study (INVEST) utilizes a unique internet-based all electronic data management system to collect data and randomly assign and prescribe antihypertensive medications (HCTZ, atenolol, verapamil SR and trendolapril). CAD is defined as either a remote confirmed MI, abnormal coronary angiogram, abnormal stress tests or classic angina pectoris. Physicians, primarily in the community, utilize the internet to generate electronic prescriptions from the assigned strategy. The system guides physicians, based on blood pressure control, to up-titrate dose and number of medications as necessary. Patients are seen every 6 weeks for the first 6 months and then biannually. Results: Data from the first 3766 women enrolled reveal an elderly population (60% ⬎65 yo), 58% Caucasian, 23% African American, 19% Hispanic, and 28% with a history of diabetes. BP data reveal diastolic and systolic control in 83% and 46% respectively, during the first year, with very few reported episodes of hypotension. BP control however, required ⱖ2 different medications in 74% of the women. Daily doses of medications ranged from: Verapamil SR 240 – 480 mg, trandolapril 2– 8 mg, atenolol 50 –100 mg and hydrochlorothiazide 25–50 mg.
Blood pressure reduction, effect duration and tolerability of the AT1-receptor blocker candesartan and the ACE inhibitor enalapril, once daily, was studied in a multicenter, doubleblind, randomised, parallel group study. A total of 395 patients, aged 20 – 80 years, with mean sitting diastolic blood pressure 95–114 mmHg and mean awake diastolic ambulatory blood pressure (ABP) ⬎85 mmHg after a 4-week placebo run-in period were randomised to 8 weeks treatment. The starting doses were candesartan cilexetil 8 mg or enalapril 10 mg. After 4 weeks the doses were doubled to 16 mg and 20 mg respectively, for all patients. At the end of the study, ABP was measured 0 –36 hours after dose. Trough blood pressure was calculated as ABP 22–24 hours post dose. The mean adjusted reduction from baseline to after 8 weeks of trough diastolic ABP was 8.7 mmHg (95% CI 7.0 –10.5) in the candesartan group vs 5.8 mmHg (95% CI 4.0 –7.6) in the enalapril group (p ⫽ 0.008). For trough systolic ABP 22–24 hours post dose, the mean adjusted reduction in the candesartan group was 13.5 mmHg (95% CI 10.9 –16.1) vs 9.9 mmHg (95% CI 7.3–12.6) in the enalapril group (p ⫽ 0.032). Mean adjusted reduction of diastolic ABP on the day of a missed dose (6 a.m.– 6 p.m.) was 8.0 mmHg (95% CI 6.7–9.3) in the candesartan group vs 4.5 mmHg (95% CI 3.2–5.9) in the enalapril group (p ⬍ 0.001). The corresponding reductions in systolic ABP were 11.4 mmHg (95% CI 9.3–13.5) with candesartan and 7.2 mmHg (95% CI 5.1– 9.4) with enalapril (p ⫽ 0.002). The proportion of patients who discontinued due to adverse events was 2.0% and 3.6% in the candesartan and enalapril groups, respectively. Once-daily candesartan cilexetil, 16 mg, was superior to enalapril, 20 mg, in reducing blood pressure at trough. At least 12 hours after a missed dose there was a persistent reduction of blood pressure during treatment with candesartan. Both treatments were well tolerated. Key Words: Candesartan; cilexetil; enalapril; ambulatory blood pressure; missed dose A017 THE ANTIPROTEINURIC EFFECT OF ENALAPRIL IS POTENTIATED BY LOSARTAN IN NORMOTENSIVE PATIENTS WITH DIABETIC NEPHROPATHY J. Arteaga*, E. Petrina, E. Anda, D. Calderon, M. Sorbet, M. Asiro´n. Dept. of Nephrology. Hospital de Navarra. Pamplona. Spain It is well known that enalapril and losartan play an important role in decreasing proteinuria in diabetic nephropathy. The aim of this work was to analyze if the addition of losartan 50 mg/day to normotensive diabetic patients with normal renal function in treatment with enalapril could be beneficial in terms of decreasing proteinuria. We selected 10 patients (4M, 6F) with type 2 diabetes, normotensives, proteinuric and with normal renal function in treatment with enalapril 10 –20 mg/day (6 –14 months). We added Losartan 50 mg/day for two months and then, enalapril was discontinued for another two months. They were their own control. There were no significant changes in weight, serum creatinine, sistolic and diastolic blood pressure.
POSTERS: Antihypertensive Drugs
Enalapril Proteinuria gr/24 h (Paired t-test)
117A
enalapril ⴙ losartan
Losartan
1,955 ⫾ 0,334
2,458 ⫾ 0,428
2,396 ⫾ 0,535 p ⬍ 0,05
p ⬍ 0,01
A decrease in proteinuric levels was observed during the combination time period. After stopping enalapril there was an increase of proteinuria that reached similar levels to the first period ones. We suggest that the additive effect of enalapril and losartan could be an elective treatment in patients with diabetic nephropathy. Long term studies are necessary to confirm the useful effect of this association. Key Words: Diabetic nephropathy; enalapril; losartan hypertension
A018 CONTROL OF BLOOD PRESSURE IN A POPULATION OF WOMEN WITH HYPERTENSION AND CAD USING AN INTERNET-BASED ELECTRONIC PRESCRIBING SYSTEM R.M. Cooper-DeHoff, E.M. Handberg-Thurmond, R.G. Marks, M. Conlon, H.R. Kolb, C.J. Pepine for the INVEST Investigators. University of Florida, Gainesville, FL Background: Adequate BP control in patients with hypertension is difficult as various reports document that only 16 –24% of patients actually achieve control despite treatment. Because coronary artery disease (CAD) is the #1 killer of women, it is imperative that focus be placed on adequate BP control in women who are hypertensive and have CAD. Data for CAD & women are lacking. To determine what is required to control BP using JNC VI criteria with lower targets for special populations, we examined data from a cohort of women with CAD enrolled in an ongoing trial. Methods: The INternational VErapamil/trandolapril Study (INVEST) utilizes a unique internet-based all electronic data management system to collect data and randomly assign and prescribe antihypertensive medications (HCTZ, atenolol, verapamil SR and trendolapril). CAD is defined as either a remote confirmed MI, abnormal coronary angiogram, abnormal stress tests or classic angina pectoris. Physicians, primarily in the community, utilize the internet to generate electronic prescriptions from the assigned strategy. The system guides physicians, based on blood pressure control, to up-titrate dose and number of medications as necessary. Patients are seen every 6 weeks for the first 6 months and then biannually. Results: Data from the first 3766 women enrolled reveal an elderly population (60% ⬎65 yo), 58% Caucasian, 23% African American, 19% Hispanic, and 28% with a history of diabetes. BP data reveal diastolic and systolic control in 83% and 46% respectively, during the first year, with very few reported episodes of hypotension. BP control however, required ⱖ2 different medications in 74% of the women. Daily doses of medications ranged from: Verapamil SR 240 – 480 mg, trandolapril 2– 8 mg, atenolol 50 –100 mg and hydrochlorothiazide 25–50 mg.