- Email: [email protected]
Assessment of adherence to ADA treatment guidelines for hypertensive patients with type 2 diabetes
132A
POSTERS: Antihypertensive Drugs
sion of SNA by the BRS was comparable in all groups. Omapatrilat, but not ramipril, increased the blood pressure sensitivity of SNA (-1.47 %SNA/mmHg) vs. placebo (-0.61 %SNA/mmHg), and shifted the setpoint (MAP5o) of SNA suppression by the BRS from 151 mmHg (placebo) to 124 mmHg. Inhibition of NEP in addition to that of ACE increases the sensitivity of the sympathetic part of the baroreceptor reflex compared with pure ACE inhibition. A possible influence of this mechanism on HR in conscious rats is obscured by other factors. Key Words: vasopeptidase inhibition, baroreceptor reflex, sympathetic nerve activity
P-262 DIFFERENTIATION OF URINARY MICROALBUMIN EXCRETION CHANGES WITH ANTIHYPERTENSIVE REGIMENS G. P. Vyssoulis, E. A. Karpanou, A. G. Marinakis, J. Rizos, J. D. Barbetseas, D. V. Cokkinos, P. K. Toutouzas. Cardiology Dept, Athens University, Athens, Greece. Nowadays, microalbuminmuria is considered as a marker of endothelial dysfunction and is associated with increase cardiovascular mortality in arterial hypertension. The aim of the present study was the comparison of microalbumin decrease after antihypertensive therapy with a b-blocker, a calcium antagonist and an angiotensin receptor blocker. The study comprised 180 consecutive, non-diabetics patients with uncomplicated , essential arterial hypertension . They were randomised to antihypertensive monotherapy for 6months with atenolol (n⫽56, 50-100 mg/day), amlodipine (n⫽59, 5-10mg/day) and irbesartan (n⫽65, 150300mg/day). Microalbuminuria, albumin/creatinine ratio (ACR) and microglobulinuria were measured before and after 6-month monotherapy. Systolic , diastolic and pulse blood pressure were similarly decreased in the three therapy groups.(35.0, 20.5 and 13.2% respectively for irbesartan, 33.8, 20.6 , 13.2% for amlodipine and 35.3, 19.8 , 15.6% for atenolol). Microalbuminuria, albumin/creatinine ratio (ACR) and microglobulinuria were significantly (p⬍0.0001)reduced only in the irbesartan group (51.7 , 52.5 and 23.4% respectively) while atenolol and amlodipine antihypertensive therapy did not reduce either mean values of microalbuminuria, albumin/creatinine ratio (ACR) and microglobulinuria or the percentage of patients with abnormal values for these parameters It is concluded that antihypertensive monotherapy with irbesartan results to significant microalbuminuria decrease, while atenolol and amlodipine have no demonstrable favorable effects, despite similar hypotensive efficacy. Key Words: microalbuminuria
P-263 COMPARATIVE DOSE-RESPONSE AND SAFETY OF EPLERENONE, ENALAPRIL, LOSARTAN, AND AMLODIPINE IN PATIENTS WITH ESSENTIAL HYPERTENSION M Weber, E Burgess, E Saunders, R Willenbrock, M Gatlin, W He, S Krause. SUNY Downstate College of Medicine, Brooklyn, NY; University of Calgary, Calgary, Alberta, Canada; University of Maryland School of Medicine, Baltimore, MD; St. Elizabeth Krankenhaus, Halle, Germany; Pharmacia Corporation, Skokie, IL. Comparative efficacy data are useful in evaluating the utility of new therapeutic agents. Data from 3 titration-to-effect antihypertensive trials comparing eplerenone (EPL) with enalapril (ENAL), losartan (LOS), and amlodipine (AML), respectively, of 16 to 24 weeks in duration were summarized to evaluate efficacy and safety data from a setting that closely mimics clinical practice. Each study provided guidelines for dose escalation if BP remained uncontrolled: EPL 50–200 mg, ENAL 10– 40 mg, LOS 50 –100 mg, and AML 2.5–10 mg. BP reduction and safety at each dose
AJH–May 2003–VOL. 16, NO. 5, PART 2
level were evaluated. Results demonstrated comparable efficacy between EPL and the comparator agents at the initial and second dose levels:
Study
EPL Dose (mg)
BP Reduction (mmHg)
Comparator Dose (mg)
BP Reduction (mmHg)
1 1 2 2 2 2 3 3
50 (n ⫽ 85) 100 (n ⫽ 43) 50 WHT (n ⫽ 18) 50 BLK (n ⫽ 27) 100 WHT (n ⫽ 20) 100 BLK (n ⫽ 32) 50 (n ⫽ 15) 100 (n ⫽ 7)
16.6/14.8 15.1/12.2 16.2/14.5 11.7/10.5 14.1/13.0 13.9/11.0 26.1/19.0 16.9/12.3
ENAL 10 (n ⫽ 72) ENAL 20 (n ⫽ 53) LOS 50 WHT (n ⫽ 19) LOS 50 BLK (n ⫽ 24) LOS 100 WHT (n ⫽ 8) LOS 100 BLK (n ⫽ 26) AML 2.5 (n ⫽ 9) AML 5 (n ⫽ 23)
17.4/16.3 15.5/13.4 13.4/10.1 7.1/14.6 10.4/14.0 3.7/7.3 10.1/12.3 16.6/13.9
WHT ⫽ white patients, BLK ⫽ black patients.
Event profiles were comparable between EPL and the comparative agents at each dosage level. Incidence of diarrhea was greater for ENAL 10 mg versus EPL 50 mg (P⫽0.029). There were no differences between EPL versus LOS, or EPL versus AML for any single event at a given dose. In conclusion, the efficacy and safety of EPL compared favorably to that of widely used antihypertensive agents. BP reductions were similar to agents compared to EPL monotherapy in these studies. Key Words: eplerenone, comparative dose response, titration-to-effect
P-264 ASSESSMENT OF ADHERENCE TO ADA TREATMENT GUIDELINES FOR HYPERTENSIVE PATIENTS WITH TYPE 2 DIABETES Matthew R. Weir, Marvin Moser. Nephrology and Clinical Research, University of Maryland School of Medicine, Baltimore, MD; Internal Medicine, Yale University School of Medicine, New Haven, CT. A survey involving 22,165 patients with hypertension and type 2 diabetes treated by 2,247 family practitioners, internists, and cardiologists was conducted to evaluate adherence to the American Diabetes Association (ADA) treatment guidelines for this population. Data on each patient’s diabetes and hypertension history, current blood pressure (BP) measurement, target BP goal, screening history for microalbuminuria/proteinuria (M/P), treatment for type 2 diabetes, and treatment for hypertension were collected through a questionnaire completed by the physician. Mean patient age was 64 years; 11,304 patients (51%) were female. Patients had a mean weight of 206 lbs and mean body mass index of 33. Eighty-eight percent of the patients were nonsmokers. Seventy-one percent (15,645) were Caucasian, 18% (3,923) were African American, 5% (1,159) were Hispanic, 3% (763) were Asian, and 3% (230) were Native American and Other. Most patients had been diagnosed with hypertension and type 2 diabetes for at least 5 years (72% and 61%, respectively). Results showed that all patients with hypertension and type 2 diabetes had been screened for M/P in accordance with ADA treatment guidelines; screening methods included the standard dipstick (34.8%), Micral 2 test strip (34.85%), or other (30.4%). In the treatment of type 2 diabetes, patients were prescribed the following therapies, often in combination: dietary control, 19,306 patients (87%); oral antidiabetic agents, 17,480 (79%); exercise, 16,322 (74%); and insulin, 4,976 (22%). Angiotensin II receptor blockers (ARBs) comprised only 19% of total antihypertensive medications prescribed, despite the ADA guideline recommendations that ARBs be given as a first-line treatment for hypertension in patients with diabetes, especially in those subjects with proteinuria. Angiotensin-converting enzyme (ACE) inhibitors comprised 35% of total antihypertensive medications prescribed. The study also found that despite treatment, only 8,201 (37%) of patients achieved the ADA-recommended target goal of a BP ⬍ 130/80 mm/Hg for patients with hypertension and type 2 diabetes. Approximately 9,974 patients (45%) had a BP of ⱖ 140/90 mm Hg, and 3,768 patients (17%) had a BP of 130/80 to 139/89 mm Hg.
AJH–May 2003–VOL. 16, NO. 5, PART 2
POSTERS: Antihypertensive Drugs
Conclusion: ADA guidelines for the treatment of hypertension in patients with type 2 diabetes are not being followed in a majority of cases. There should be a reemphasis of these guidelines. Key Words: diabetes, angiotensin II receptor antagonists, ADA treatment guidelines
P-265 COMPARISON OF NOCTURNAL DOSING OF DILTIAZEM ER AND RAMIPRIL ON EARLY MORNING BLOOD PRESSURE, HEART RATE AND THE RATE-PRESSURE PRODUCT William B White, David H.G Smith, Theophilus J Gana, Luz G Pascual, Kenneth S Albert. Medicine, University of Connecticut School of Medicine, Farmington, CT; Medicine, University of California, Irvine, CA; Clinical Development, Biovail Corporation, Chantilly, VA. The early morning is a time of enhanced cardiovascular risk and is associated with steep increases in both blood pressure (BP) and heart rate. Blood pressure control and outcome may be improved by nocturnal dosing of antihypertensive therapy as was recently reported in the HOPE trial. However, little is known about comparative effects of nighttime dosing of antihypertensive therapy. We compared a novel formulation, diltiazem ER, to ramipril, both dosed at bedtime in a multicenter, randomized, double-blind, parallel-group, dose-to-effect study in 261 patients with Stages I-II hypertension. The key efficacy endpoints were changes from baseline in BP, heart rate and the heart rate-systolic BP product (rate-pressure product) measured by ambulatory BP monitoring during the first 4 hours after awakening and for the entire 24-hour period. Patients were randomized to receive either diltiazem ER (240 mg to 360 mg to 540 mg QD; n⫽130) or ramipril (5 mg to 10 mg to 20 mg QD; n⫽131) for 10 weeks. Titration of dose occurred when the clinic BP was ⱖ 130/85 mm Hg. In both groups, 76% of patients were at the highest dose at the end of 10 weeks of treatment. As shown in the Table, diltiazem ER was associated with significantly greater reductions in mean BP during the first 4 hours after awakening compared to ramipril. The mean reductions in heart rate and rate-pressure product during all time intervals and for the 24-hour mean diastolic BP were also significantly larger (p⬍0.001 each) for diltiazem ER compared to ramipril. Tolerability and adverse events were similar for the 2 treatment groups. Thus, nocturnal dosing of diltiazem ER was more effective than nocturnal dosing of ramipril in reducing the early morning BP, heart rate and rate-pressure product as well as 24 hour diastolic BP, heart rate, and rate-pressure product.
Parameter
Diltiazem ER
Ramipril
P-Value
4-hour Post-awakening Values BP (mmHg) ⫺18/⫺15 ⫾ 1/1 ⫺13/⫺8 ⫾ 1/1 0.002/⬍0.001 Heart rate (beats/min) ⫺9 ⫾ 0.7 ⫺3 ⫾ 0.7 ⬍0.001 Rate-pressure product (beats/ ⫺2518 ⫾ 128 ⫺1393 ⫾ 127 ⬍0.001 min.mmHg) 24-hour Mean Values BP (mmHg) ⫺11/⫺10 ⫾ 1/1 ⫺10/⫺7 ⫾ 1/1 0.564/⬍0.001 Heart rate (beats/min) ⫺7 ⫾ 0.5 ⫺1 ⫾ 0.5 ⬍0.001 Rate-pressure product (beats/ ⫺1789 ⫾ 93 ⫺917 ⫾ 92 ⬍0.001 min.mmHg)
Key Words: nocturnal antihypertensive dosing, diltiazem ER, ramipril
133A
P-266 COMPARISON OF NISOLDIPINE ER VERSUS AMLODIPINE FOR THE TREATMENT OF AFRICANAMERICAN PATIENTS WITH HYPERTENSION William B White, Elijah Saunders. Section of Hypertension and Clinical Pharmacology, University of Connecticut School of Medicine, Farmington, CT; Division of Hypertension, University of Maryland School of Medicine, Baltimore, MD. Calcium channel blockers (CCBs) are widely used, either alone or in combination with other agents, to treat hypertension in the AfricanAmerican population. Nisoldipine ER is a vasculoselective dihydropyridine CCB that is presently dosed from 10-60 mg daily and has a lower acquisition cost compared to most other CCBs. We studied nisoldipine ER (20 to 60 mg) and amlodipine (5 to 10 mg) in hypertensive AfricanAmerican men and women (mean age, 52 years, baseline clinic BP range, 140-200/95-114 mmHg) using clinic and 24-hour ambulatory BP monitoring to compare their safety and efficacy in this population. There were 193 patients randomized to nisoldipine ER (n ⫽ 92) or amlodipine (n ⫽ 101) at 18 clinical sites in the USA. The design was titration to effect at 4 week intervals to achieve a seated office BP ⬍ 140/90 mmHg. This resulted in 74% of the patients on ⱖ 40 mg of nisoldipine and 82% of the patients on 10 mg of amlodipine. Changes from baseline in ambulatory and clinic BP and heart rate in the modified intent-to-treat population are shown in the Table (mean ⫾ SE). Parameter Ambulatory (24h) Diastolic mmHg Systolic mmHg Heart rate, bpm Clinic, seated Diastolic mmHg Systolic mmHg Heart rate, bpm
Difference in Nisoldipine Amlodipine Treatments 90% CI
P-Value
⫺16.0 (2.3) ⫺15.0 (2.3) ⫺23.1 (2.7) ⫺19.9 (2.7) ⫺1.7 (2.4) ⫺3.1 (2.4)
⫺1.0 (1.5) ⫺3.2 (1.7) 1.4 (1.6)
(⫺3.5, 1.5) 0.500 (⫺6.0, ⫺0.3) 0.067 (⫺1.2, 4.0) 0.362
⫺13.7 (1.9) ⫺14.7 (1.9) ⫺19.4 (2.9) ⫺19.9 (2.9) ⫺0.6 (1.8) 1.2 (1.8)
1.0 (1.2) 0.5 (1.9) ⫺1.8 (1.1)
(⫺1.0, 3.0) (⫺2.6, 3.6) (⫺3.6, 0.1)
0.424 0.784 0.118
No significant differences were noted in the safety and tolerability between treatments. The most prevalent adverse events were headache (nisoldipine, 14%; amlodipine, 15%) and lower extremity edema (nisoldipine, 12%; amlodipine, 10%). These data show that substantial changes in BP occurred for both the clinic and ambulatory BP for each treatment arm. The reduction in 24-hour systolic BP was somewhat greater (3.2 mmHg) with nisoldipine ER compared to amlodipine in African-American patients with hypertension. Key Words: nisoldipine ER, calcium antagonists, African-Americans
P-267 ADDITION OF EPLERENONE TO CALCIUM CHANNEL BLOCKERS AND BETA BLOCKERS IMPROVES BLOOD PRESSURE CONTROL R Willenbrock, W van Mieghem, V von Behren, I Balazovjech, C Lademacher, M Gatlin, S Krause. St. Elizabeth Krankenhaus, Halle, Germany; Dienst Cardio, St. Jan Ziekenhuis, Genk, Belgium; Intermed, Wiesbaden, Germany; Faculty Hospital, Bratislava, Slovakia (Slovak Republic); Pharmacia Corporation, Skokie, IL. Background: Antihypertensive monotherapy provides BP control in as few as 30-60% of patients. Therefore, JNC-VI recommends combining antihypertensive agents, preferably those with different mechanisms of action, to enhance BP control. This study evaluated adding the selective aldosterone blocker eplerenone (EPL) to patients inadequately controlled on either calcium-channel blockers (CCB) or -blockers (BB). Methods: This was an 8-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study in patients with mild-to-moder-
POSTERS: Antihypertensive Drugs
sion of SNA by the BRS was comparable in all groups. Omapatrilat, but not ramipril, increased the blood pressure sensitivity of SNA (-1.47 %SNA/mmHg) vs. placebo (-0.61 %SNA/mmHg), and shifted the setpoint (MAP5o) of SNA suppression by the BRS from 151 mmHg (placebo) to 124 mmHg. Inhibition of NEP in addition to that of ACE increases the sensitivity of the sympathetic part of the baroreceptor reflex compared with pure ACE inhibition. A possible influence of this mechanism on HR in conscious rats is obscured by other factors. Key Words: vasopeptidase inhibition, baroreceptor reflex, sympathetic nerve activity
P-262 DIFFERENTIATION OF URINARY MICROALBUMIN EXCRETION CHANGES WITH ANTIHYPERTENSIVE REGIMENS G. P. Vyssoulis, E. A. Karpanou, A. G. Marinakis, J. Rizos, J. D. Barbetseas, D. V. Cokkinos, P. K. Toutouzas. Cardiology Dept, Athens University, Athens, Greece. Nowadays, microalbuminmuria is considered as a marker of endothelial dysfunction and is associated with increase cardiovascular mortality in arterial hypertension. The aim of the present study was the comparison of microalbumin decrease after antihypertensive therapy with a b-blocker, a calcium antagonist and an angiotensin receptor blocker. The study comprised 180 consecutive, non-diabetics patients with uncomplicated , essential arterial hypertension . They were randomised to antihypertensive monotherapy for 6months with atenolol (n⫽56, 50-100 mg/day), amlodipine (n⫽59, 5-10mg/day) and irbesartan (n⫽65, 150300mg/day). Microalbuminuria, albumin/creatinine ratio (ACR) and microglobulinuria were measured before and after 6-month monotherapy. Systolic , diastolic and pulse blood pressure were similarly decreased in the three therapy groups.(35.0, 20.5 and 13.2% respectively for irbesartan, 33.8, 20.6 , 13.2% for amlodipine and 35.3, 19.8 , 15.6% for atenolol). Microalbuminuria, albumin/creatinine ratio (ACR) and microglobulinuria were significantly (p⬍0.0001)reduced only in the irbesartan group (51.7 , 52.5 and 23.4% respectively) while atenolol and amlodipine antihypertensive therapy did not reduce either mean values of microalbuminuria, albumin/creatinine ratio (ACR) and microglobulinuria or the percentage of patients with abnormal values for these parameters It is concluded that antihypertensive monotherapy with irbesartan results to significant microalbuminuria decrease, while atenolol and amlodipine have no demonstrable favorable effects, despite similar hypotensive efficacy. Key Words: microalbuminuria
P-263 COMPARATIVE DOSE-RESPONSE AND SAFETY OF EPLERENONE, ENALAPRIL, LOSARTAN, AND AMLODIPINE IN PATIENTS WITH ESSENTIAL HYPERTENSION M Weber, E Burgess, E Saunders, R Willenbrock, M Gatlin, W He, S Krause. SUNY Downstate College of Medicine, Brooklyn, NY; University of Calgary, Calgary, Alberta, Canada; University of Maryland School of Medicine, Baltimore, MD; St. Elizabeth Krankenhaus, Halle, Germany; Pharmacia Corporation, Skokie, IL. Comparative efficacy data are useful in evaluating the utility of new therapeutic agents. Data from 3 titration-to-effect antihypertensive trials comparing eplerenone (EPL) with enalapril (ENAL), losartan (LOS), and amlodipine (AML), respectively, of 16 to 24 weeks in duration were summarized to evaluate efficacy and safety data from a setting that closely mimics clinical practice. Each study provided guidelines for dose escalation if BP remained uncontrolled: EPL 50–200 mg, ENAL 10– 40 mg, LOS 50 –100 mg, and AML 2.5–10 mg. BP reduction and safety at each dose
AJH–May 2003–VOL. 16, NO. 5, PART 2
level were evaluated. Results demonstrated comparable efficacy between EPL and the comparator agents at the initial and second dose levels:
Study
EPL Dose (mg)
BP Reduction (mmHg)
Comparator Dose (mg)
BP Reduction (mmHg)
1 1 2 2 2 2 3 3
50 (n ⫽ 85) 100 (n ⫽ 43) 50 WHT (n ⫽ 18) 50 BLK (n ⫽ 27) 100 WHT (n ⫽ 20) 100 BLK (n ⫽ 32) 50 (n ⫽ 15) 100 (n ⫽ 7)
16.6/14.8 15.1/12.2 16.2/14.5 11.7/10.5 14.1/13.0 13.9/11.0 26.1/19.0 16.9/12.3
ENAL 10 (n ⫽ 72) ENAL 20 (n ⫽ 53) LOS 50 WHT (n ⫽ 19) LOS 50 BLK (n ⫽ 24) LOS 100 WHT (n ⫽ 8) LOS 100 BLK (n ⫽ 26) AML 2.5 (n ⫽ 9) AML 5 (n ⫽ 23)
17.4/16.3 15.5/13.4 13.4/10.1 7.1/14.6 10.4/14.0 3.7/7.3 10.1/12.3 16.6/13.9
WHT ⫽ white patients, BLK ⫽ black patients.
Event profiles were comparable between EPL and the comparative agents at each dosage level. Incidence of diarrhea was greater for ENAL 10 mg versus EPL 50 mg (P⫽0.029). There were no differences between EPL versus LOS, or EPL versus AML for any single event at a given dose. In conclusion, the efficacy and safety of EPL compared favorably to that of widely used antihypertensive agents. BP reductions were similar to agents compared to EPL monotherapy in these studies. Key Words: eplerenone, comparative dose response, titration-to-effect
P-264 ASSESSMENT OF ADHERENCE TO ADA TREATMENT GUIDELINES FOR HYPERTENSIVE PATIENTS WITH TYPE 2 DIABETES Matthew R. Weir, Marvin Moser. Nephrology and Clinical Research, University of Maryland School of Medicine, Baltimore, MD; Internal Medicine, Yale University School of Medicine, New Haven, CT. A survey involving 22,165 patients with hypertension and type 2 diabetes treated by 2,247 family practitioners, internists, and cardiologists was conducted to evaluate adherence to the American Diabetes Association (ADA) treatment guidelines for this population. Data on each patient’s diabetes and hypertension history, current blood pressure (BP) measurement, target BP goal, screening history for microalbuminuria/proteinuria (M/P), treatment for type 2 diabetes, and treatment for hypertension were collected through a questionnaire completed by the physician. Mean patient age was 64 years; 11,304 patients (51%) were female. Patients had a mean weight of 206 lbs and mean body mass index of 33. Eighty-eight percent of the patients were nonsmokers. Seventy-one percent (15,645) were Caucasian, 18% (3,923) were African American, 5% (1,159) were Hispanic, 3% (763) were Asian, and 3% (230) were Native American and Other. Most patients had been diagnosed with hypertension and type 2 diabetes for at least 5 years (72% and 61%, respectively). Results showed that all patients with hypertension and type 2 diabetes had been screened for M/P in accordance with ADA treatment guidelines; screening methods included the standard dipstick (34.8%), Micral 2 test strip (34.85%), or other (30.4%). In the treatment of type 2 diabetes, patients were prescribed the following therapies, often in combination: dietary control, 19,306 patients (87%); oral antidiabetic agents, 17,480 (79%); exercise, 16,322 (74%); and insulin, 4,976 (22%). Angiotensin II receptor blockers (ARBs) comprised only 19% of total antihypertensive medications prescribed, despite the ADA guideline recommendations that ARBs be given as a first-line treatment for hypertension in patients with diabetes, especially in those subjects with proteinuria. Angiotensin-converting enzyme (ACE) inhibitors comprised 35% of total antihypertensive medications prescribed. The study also found that despite treatment, only 8,201 (37%) of patients achieved the ADA-recommended target goal of a BP ⬍ 130/80 mm/Hg for patients with hypertension and type 2 diabetes. Approximately 9,974 patients (45%) had a BP of ⱖ 140/90 mm Hg, and 3,768 patients (17%) had a BP of 130/80 to 139/89 mm Hg.
AJH–May 2003–VOL. 16, NO. 5, PART 2
POSTERS: Antihypertensive Drugs
Conclusion: ADA guidelines for the treatment of hypertension in patients with type 2 diabetes are not being followed in a majority of cases. There should be a reemphasis of these guidelines. Key Words: diabetes, angiotensin II receptor antagonists, ADA treatment guidelines
P-265 COMPARISON OF NOCTURNAL DOSING OF DILTIAZEM ER AND RAMIPRIL ON EARLY MORNING BLOOD PRESSURE, HEART RATE AND THE RATE-PRESSURE PRODUCT William B White, David H.G Smith, Theophilus J Gana, Luz G Pascual, Kenneth S Albert. Medicine, University of Connecticut School of Medicine, Farmington, CT; Medicine, University of California, Irvine, CA; Clinical Development, Biovail Corporation, Chantilly, VA. The early morning is a time of enhanced cardiovascular risk and is associated with steep increases in both blood pressure (BP) and heart rate. Blood pressure control and outcome may be improved by nocturnal dosing of antihypertensive therapy as was recently reported in the HOPE trial. However, little is known about comparative effects of nighttime dosing of antihypertensive therapy. We compared a novel formulation, diltiazem ER, to ramipril, both dosed at bedtime in a multicenter, randomized, double-blind, parallel-group, dose-to-effect study in 261 patients with Stages I-II hypertension. The key efficacy endpoints were changes from baseline in BP, heart rate and the heart rate-systolic BP product (rate-pressure product) measured by ambulatory BP monitoring during the first 4 hours after awakening and for the entire 24-hour period. Patients were randomized to receive either diltiazem ER (240 mg to 360 mg to 540 mg QD; n⫽130) or ramipril (5 mg to 10 mg to 20 mg QD; n⫽131) for 10 weeks. Titration of dose occurred when the clinic BP was ⱖ 130/85 mm Hg. In both groups, 76% of patients were at the highest dose at the end of 10 weeks of treatment. As shown in the Table, diltiazem ER was associated with significantly greater reductions in mean BP during the first 4 hours after awakening compared to ramipril. The mean reductions in heart rate and rate-pressure product during all time intervals and for the 24-hour mean diastolic BP were also significantly larger (p⬍0.001 each) for diltiazem ER compared to ramipril. Tolerability and adverse events were similar for the 2 treatment groups. Thus, nocturnal dosing of diltiazem ER was more effective than nocturnal dosing of ramipril in reducing the early morning BP, heart rate and rate-pressure product as well as 24 hour diastolic BP, heart rate, and rate-pressure product.
Parameter
Diltiazem ER
Ramipril
P-Value
4-hour Post-awakening Values BP (mmHg) ⫺18/⫺15 ⫾ 1/1 ⫺13/⫺8 ⫾ 1/1 0.002/⬍0.001 Heart rate (beats/min) ⫺9 ⫾ 0.7 ⫺3 ⫾ 0.7 ⬍0.001 Rate-pressure product (beats/ ⫺2518 ⫾ 128 ⫺1393 ⫾ 127 ⬍0.001 min.mmHg) 24-hour Mean Values BP (mmHg) ⫺11/⫺10 ⫾ 1/1 ⫺10/⫺7 ⫾ 1/1 0.564/⬍0.001 Heart rate (beats/min) ⫺7 ⫾ 0.5 ⫺1 ⫾ 0.5 ⬍0.001 Rate-pressure product (beats/ ⫺1789 ⫾ 93 ⫺917 ⫾ 92 ⬍0.001 min.mmHg)
Key Words: nocturnal antihypertensive dosing, diltiazem ER, ramipril
133A
P-266 COMPARISON OF NISOLDIPINE ER VERSUS AMLODIPINE FOR THE TREATMENT OF AFRICANAMERICAN PATIENTS WITH HYPERTENSION William B White, Elijah Saunders. Section of Hypertension and Clinical Pharmacology, University of Connecticut School of Medicine, Farmington, CT; Division of Hypertension, University of Maryland School of Medicine, Baltimore, MD. Calcium channel blockers (CCBs) are widely used, either alone or in combination with other agents, to treat hypertension in the AfricanAmerican population. Nisoldipine ER is a vasculoselective dihydropyridine CCB that is presently dosed from 10-60 mg daily and has a lower acquisition cost compared to most other CCBs. We studied nisoldipine ER (20 to 60 mg) and amlodipine (5 to 10 mg) in hypertensive AfricanAmerican men and women (mean age, 52 years, baseline clinic BP range, 140-200/95-114 mmHg) using clinic and 24-hour ambulatory BP monitoring to compare their safety and efficacy in this population. There were 193 patients randomized to nisoldipine ER (n ⫽ 92) or amlodipine (n ⫽ 101) at 18 clinical sites in the USA. The design was titration to effect at 4 week intervals to achieve a seated office BP ⬍ 140/90 mmHg. This resulted in 74% of the patients on ⱖ 40 mg of nisoldipine and 82% of the patients on 10 mg of amlodipine. Changes from baseline in ambulatory and clinic BP and heart rate in the modified intent-to-treat population are shown in the Table (mean ⫾ SE). Parameter Ambulatory (24h) Diastolic mmHg Systolic mmHg Heart rate, bpm Clinic, seated Diastolic mmHg Systolic mmHg Heart rate, bpm
Difference in Nisoldipine Amlodipine Treatments 90% CI
P-Value
⫺16.0 (2.3) ⫺15.0 (2.3) ⫺23.1 (2.7) ⫺19.9 (2.7) ⫺1.7 (2.4) ⫺3.1 (2.4)
⫺1.0 (1.5) ⫺3.2 (1.7) 1.4 (1.6)
(⫺3.5, 1.5) 0.500 (⫺6.0, ⫺0.3) 0.067 (⫺1.2, 4.0) 0.362
⫺13.7 (1.9) ⫺14.7 (1.9) ⫺19.4 (2.9) ⫺19.9 (2.9) ⫺0.6 (1.8) 1.2 (1.8)
1.0 (1.2) 0.5 (1.9) ⫺1.8 (1.1)
(⫺1.0, 3.0) (⫺2.6, 3.6) (⫺3.6, 0.1)
0.424 0.784 0.118
No significant differences were noted in the safety and tolerability between treatments. The most prevalent adverse events were headache (nisoldipine, 14%; amlodipine, 15%) and lower extremity edema (nisoldipine, 12%; amlodipine, 10%). These data show that substantial changes in BP occurred for both the clinic and ambulatory BP for each treatment arm. The reduction in 24-hour systolic BP was somewhat greater (3.2 mmHg) with nisoldipine ER compared to amlodipine in African-American patients with hypertension. Key Words: nisoldipine ER, calcium antagonists, African-Americans
P-267 ADDITION OF EPLERENONE TO CALCIUM CHANNEL BLOCKERS AND BETA BLOCKERS IMPROVES BLOOD PRESSURE CONTROL R Willenbrock, W van Mieghem, V von Behren, I Balazovjech, C Lademacher, M Gatlin, S Krause. St. Elizabeth Krankenhaus, Halle, Germany; Dienst Cardio, St. Jan Ziekenhuis, Genk, Belgium; Intermed, Wiesbaden, Germany; Faculty Hospital, Bratislava, Slovakia (Slovak Republic); Pharmacia Corporation, Skokie, IL. Background: Antihypertensive monotherapy provides BP control in as few as 30-60% of patients. Therefore, JNC-VI recommends combining antihypertensive agents, preferably those with different mechanisms of action, to enhance BP control. This study evaluated adding the selective aldosterone blocker eplerenone (EPL) to patients inadequately controlled on either calcium-channel blockers (CCB) or -blockers (BB). Methods: This was an 8-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study in patients with mild-to-moder-