Long-term efficacy and tolerability of telmisartan as monotherapy and in combination with other antihypertensive medications

106A

POSTERS: Antihypertensive Drugs

randomization in three groups receiving an acute administration of Nifedipine GITS (30mg) (NGITS), or Nifedipine capsule 10mg (Ncap) or placebo (PL). Each administration was separated by one week with placebo daily intake. Blood pressure (BP) and heart rate measurements were performed at H0 then repeated at H1/2, H1, H2, H4, H6, H8 then H24 after placebo or drugs intake during a 24-hour hospitalization. Catecholamines dosage were simultaneously repeated together with BP recordings in a temperature-regulated room. A 2-way ANOVA for repeated measure was used. Results : Norepinephrine, but not epinephrine nor dopamine rose significantly (p⬍0.02) following Ncap by comparison with NGITS and PL with no difference between NGITS and PL. BP decreased significantly from H1/2 to H4 with Ncap, and at H4 and H24 with NGITS. HR increased at H1/2 and H1 with Ncap and did not change with NGITS. Summary : An acute administration of Nifedipine GITS (30mg) significantly decreased BP at the 4th and 24th hours following administration, with no alteration of catecholamines while nifedipine capsule (10mg) decreased BP from the 30th minute to the 4th hour with increase in HR until H1. Among the catecholamines, only norepinephrine increased significantly following Ncap in parallel with BP alterations with no change following NGITS. Conclusion: While nifedipine capsule 10mg increases plasma norepinephrine during the first 4 hours after an acute administration, slow release nifedipine GITS does not induce any change in plasma catecholamine. Key Words: catecholamine, arterial hypertension, nifedipine

P-232 LONG-TERM EFFICACY AND TOLERABILITY OF TELMISARTAN AS MONOTHERAPY AND IN COMBINATION WITH OTHER ANTIHYPERTENSIVE MEDICATIONS Joel M. Neutel, Christiane Klein, Thomas W. Meinicke, Helmut Schumacher. 1Orange County Heart Institute & Research Center, Orange, CA, United States, 2Kuenzing, Germany, 3Clinical Research, Boehringer Ingelheim Pharma KG, Biberach, Germany, 4Medical Data Services, Boehringer Ingelheim Pharma KG, Ingelheim,, Germany This open-label, multicenter, extension study assessed the efficacy and tolerability of telmisartan 80 mg administered alone or with hydrochlorothiazide (HCTZ) and/or other antihypertensive agents over a maximal 1-year treatment period. Of the 690 patients with mild-to-moderate hypertension completing the preceding 6-week, randomized study (comparing telmisartan 80 mg with losartan 50 mg/HCTZ 12.5 mg combination therapy), 490 patients (71.0%) continued in this extension study. A fixed-titration regimen was employed: all patients received telmisartan 80 mg initially, with stepwise addition of HCTZ 12.5 mg, HCTZ 25 mg, and/or other antihypertensives to attain DBP control (⬍90 mmHg). 489 patients received treatment and 483 patients were included in the intent-to-treat analysis. 57.3% (277/483) of patients were maintained on telmisartan 80 mg monotherapy throughout the study and 68.6% (194/ 283) of them reached DBP control at the final visit. A subgroup analysis by pretreatment (telmisartan 80 mg vs losartan 50 mg ⫹ HCTZ 12.5 mg) in the preceding study did not reveal any difference in maintenance rate of telmisartan monotherapy and control rates in the present study. 17.8% (86/483) of patients were titrated to telmisartan 80 mg ⫹ HCTZ 12.5 mg and 55.8% (48/86) reached DBP control. 54.7% (47/86) titrated to telmisartan 80 mg ⫹ HCTZ 25 mg and 64.7% (22/34) titrated to telmisartan 80 mg ⫹ other antihypertensive ⫾ HCTZ (12.5 or 25 mg) reached DBP control. The DBP and SBP reductions observed in the preceding randomized study continued during extension treatment. Overall, a further decrease by a mean of 4.5 (SD ⫾ 10.0) mmHg in DBP and by a mean of 5.7 (SD ⫾ 16.4) mmHg in SBP was observed. Progressively

AJH–April 2001–VOL. 14, NO. 4, PART 2

greater blood pressure reductions occurred with the sequential addition of HCTZ and other antihypertensives. Adding HCTZ 12.5 mg to telmisartan 80 mg was particularly effective at enhancing antihypertensive efficacy. All treatments were well tolerated. In conclusion, telmisartan 80 mg administered alone or with HCTZ (12.5 or 25 mg) and/or other antihypertensives maintains a clinically significant therapeutic effect over the long term in patients with mild-tomoderate hypertension. Key Words: Telmisartan, Combination therapy, Hydrochlorothiazide

P-233 COMPARISON OF THE ANTIHYPERTENSIVE EFFICACY AND TOLERABILITY OF CANDESARTAN CILEXETIL AND ANGIOTENSIN-CONVERTING ENZYMZE INHIBITOR THERAPY IN PRIMARY HYPERTENSION : THE CHAMPION STUDY Robert Lins, Jean-Marie Krzesinski, Guy Vandenhoven, Christophe J. Giot. 1Nephrology, A.Z. Stuivenberg, Antwerpen, Belgium, 2Internal Medecine, CHU Liege, Liege, Belgium, 3Medical, AstraZeneca, Brussels, Belgium The aim of the study was to compare the efficacy and tolerability of candesartan cilexetil (C)with an angiotensin-converting enzyme inhibitor therapy (A), with the addition of hydrochlorothiazide (HCTZ) when necessary, in patients with mild to moderate primary hypertension (sitting diastolic blood pressure [sitDBP] ⬍ 115 mmHg and/or sitting systolic blood pressure [sitSBP] ⬍ 200 mmHg).Patients unsuccessfully treated with one or more antihypertensives or suffering from side effects were included in this multicenter (856) trial. Patients (n⫽ 5116) were randomized into a 20-week treatment phase and were started on oral C 8 mg, o.d., or A low dose. The dose of C was increased to 16 mg,o.d., and that of A to high dose at week 4, 8 and 12 if sitDBP was ⱖ90 mmHg and/or sitSBP ⱖ140 mmHg. If blood pressure remained uncontrolled on maximum doses of C or A at week 8 and 12, HCTZ 12,5 mg was added to the treatment regimen. At week 12, in uncontrolled patients, the dose of HCTZ was increased to 25 mg. The patients were randomized 4/5 to the C group and 1/5 to the A group. The major end-points were the changes in mean sitDBP from baseline and the response rate calculated at weeks 4, 8, 12 and 20. A patient was considered a responder when sitDBP and sitSBP fall under the thresholds of 90 and 140 mmHg respectively or in when one of the pressures decreases with a minimum of 10 mmHg from one visit to the other. A total of 5116 patients (2311 men,2805 women,mean age 58.8 years) were included in the intention to treat analysis dataset. After 12 weeks of treatment, a difference of 1.2 mmHg in the decrease of sitDBP in favor of C (p⫽ 0.0009) has been noted which has been maintained until the end of the study. At week 20, the percentage of responders was 93.4 in the C group and 90.3 in the A group (p⫽ 0.0022), the sitDBP was 83.3 mmHg and 84.6 mmHg in the C and A group respectively (p⫽0.0031) and the sitSBP was 139.5 mmHg and 141.4 mmHg in the C and A group respectively (p⫽0.0335). Finally in this study, 697 patients mentioned at least one adverse event 13.4% and 15.1% (p⬎0.05) in the C group and A group respectively. This study performed in a primary care setting showed a significantly higher responder rate in the Candesartan group than in the ACE inhibitor group and secondly that Candesartan was at least as safe and as well tolerated than ACE inhibithors. Grant/Research Support - AstraZeneca, Belgium Key Words: candesartan cilexetil, angiotensin converting enzyme inhibitor, drugs