Pulse pressure changes with six classes of antihypertensive agents and placebo in Whites and African Americans by age

AJH–APRIL 2000 –VOL. 13, NO. 4, PART 2

POSTERS: Clinical Trials

ues and country, was ⫺1.9 mmHg (95% CI: ⫺2.7, ⬀). The CI excluded a treatment difference of 3.0 mmHg or more. Consistent results were found in the analyses of secondary endpoints. Analysis of morning ABPM DBP means (06:00 –11: 59) and of trough cuff DBP confirmed the non-inferiority of telmisartan 80 mg versus losartan 50 mg/HCTZ 12.5 mg by ruling out a clinically meaningful difference of 3 mmHg with 95% confidence. Both treatments were well tolerated. This study shows that telmisartan 80 mg is as effective as a fixed dose combination of losartan 50 mg/HCTZ 12.5 mg with regard to the reduction in 24-h mean ABPM DBP in patients with mild-to-moderate hypertension. Furthermore, both treatments provided blood pressure control during the early morning period, when patients are most vulnerable to cardiovascular events. Key Words: Telmisartan; losartan; hydrochlorothiazide; angiotensin II antagonist; ambulatory blood pressure monitoring B014 PULSE PRESSURE CHANGES WITH SIX CLASSES OF ANTIHYPERTENSIVE AGENTS AND PLACEBO IN WHITES AND AFRICAN AMERICANS BY AGE W.C. Cushman*, B.J. Materson*, D.J. Reda, and D.W. Williams for the Veteran Affairs (VA) Cooperative Study Group on Antihypertensive Agents. VA Medical Center, Memphis, TN Age-race groups have differing systolic (SBP) and diastolic (DBP) blood pressure responses to antihypertensive medications. Since pulse pressure (PP) has been more strongly associated with cardiovascular events than SBP, DBP, or mean arterial pressure, we compared the PP changes in 1,292 men with untreated DBP hypertension (DBP 95–109 mm Hg) randomized to hydrochlorothiazide (HC) 12.5–50 mg QD, atenolol (AT) 25–100 mg QD, captopril (CP) 12.5–50 mg BID, clonidine (CL) 0.1– 0.3 mg BID, diltiazem SR (DL) 60 –180 mg BID, prazosin (PR) 2–10 mg BID, and placebo (PB). Mean (⫾SD) baseline SBP, DBP, and PP were 152⫾14, 99⫾3, and 52.9⫾12.9 mm Hg, respectively. The table reports mean PP change (mm Hg) for all patients and by age-race subgroup during 3 months of treatment [Y⫽younger (⬍60 yrs), O⫽older (ⱖ60 yrs), W⫽white, AA⫽African American].

AII Y-W Y-AA O-W O-AA

p

HC

AT

CP

CL

DL

PR

PB

.0001 .0224 .0001 .0001 .0013

⫺3.5 ⫺4.5 ⫺4.0 ⫺2.2 ⫺4.2

1.3 ⫺1.2 3.8 0.8 1.9

0.2 ⫺0.3 1.1 ⫺0.1 0.3

⫺4.0 ⫺3.6 ⫺3.9 ⫺3.7 ⫺4.7

1.1 1.4 0.2 1.8 0.5

⫺1.2 1.2 0.1 ⫺3.1 ⫺1.6

2.7 ⫺0.2 3.1 3.8 2.2

In all, CL reduced PP significantly more than all groups but HC, and HC reduced PP more than all but CL and PR. In Y-W (n⫽246), follow-up tests were not significant; in Y-AA (n⫽291), HC and CL were significantly different from AT and PL; in O-W (n⫽408), CL reduced PP more than DL and PL, and PR and HC more than PL; in O-AA (n⫽330), CL and HC reduced PP more than AT and PL. Conclusions: In this study of 6 classes of agents, all age-race groups reduced PP most with a central agonist and a diuretic (O-W also did with an alpha blocker).

59A

Key Words: Pulse pressure; antihypertensive agents; age; race; randomized controlled trial B015 ROLE OF CANDESARTAN, LISINOPRIL AND THEIR COMBINATION ON BLOOD PRESSURE AND ALBUMINURIA IN HYPERTENSIVE MICROALBUMINURIC DIABETIC SUBJECTS M.E. Cooper*, C.E. Mogensen†, for the CALM study group. University of Melbourne, Australia, †Aarhus University Hospital, Denmark Reduction of blood pressure and urinary albumin/creatinine ratio (UACR) was studied in the CALM trial, a multicentre, randomised, double-blind trial with candesartan, lisinopril and their combination. A total of 199 hypertensive (DBP 90 –110 mmHg) type 2 diabetic patients with microalbuminuria (UACR 2.5–25 mg/mmol) were randomised following a 4 week placebo run-in period. The patients were randomised to either the ACE I lisinopril (L) 20 mg o.d. or the AT1 blocker candesartan cilexitil (C) 16 mg o.d. for 12 weeks followed by an additional 12 weeks of the same monotherapy or the combination of C⫹L. There were no imbalances in baseline characteristics among the different treatment groups; mean age 60 years, ⬃35% female, BMI ⬃30 kg/m2, 8 year history of hypertension and a 9 year history of diabetes. Mean baseline BP was 163/96 mmHg and UACR 10 mg/mmol. After 12 weeks of monotherapy, both L (n⫽99) and C (n⫽98) reduced sitting BP (C, 12.4/9.5mmHg p⬍0.001, L, 15.7/9.7mmHg, p⬍0.001) and UACR (C 29% p⬍0.001, L 45% p⬍0.001) with no significant difference between the treatment groups. During the 12–24 week period there was no further decrease in BP with monotherapy but C⫹L resulted in a further decrease in blood pressure (n⫽49, 10.6/ 6.0mmHg, p⬍0.001). No further significant reduction in UACR was observed with either continued monotherapy or combination treatment but there was a non-significant trend for a further reduction on combination treatment. Both drugs and their combination were well tolerated and no difference in adverse event profile was observed among the three treatment groups. Importantly, no adverse effects were observed in the combination treatment group such as acute deterioration in renal function or symptomatic hypotension. AT1 receptor blockade with C is as effective as ACE inhibition with L in reducing blood pressure and microalbuminuria in hypertensive type 2 diabetic subjects. The combination of the AT1 blocker candesartan and the ACE-I lisinopril is a well-tolerated and highly effective treatment for reducing BP in hypertensive diabetic subjects. Key Words: Candesartan; lisinopril; diabetes; microalbuminuria B016 OMAPATRILAT IN ELDERLY HYPERTENSIVE PATIENTS: A PLACEBO-CONTROLLED TRIAL J.L. Izzo, Jr.*1, T.S. Herman, S. Nash, J. McKenney, R.A. Reeves*2. 1State University of New York at Buffalo; and 2B-MS PRI, Princeton, NJ