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Comparative effects of lercanidipine and hydrochlorothiazide on hypertension-related cardiac and vascular structural alterations
AJH–April 2002–VOL. 15, NO. 4, PART 2
medication and time of treatment in patients receiving only one drug. We studied 275 patients with mild-moderate essential hypertension (115 men), 53.2⫾14.1 (mean⫾SD) years of age, who underwent antihypertensive treatment in monotherapy for at least 3 months. BP was measured at 20-minute intervals during the day (07:00 to 23:00 hours) and every 30-minutes at night for 48 consecutive hours. Physical activity was simultaneously monitored at 1-minute intervals by wrist actigraphy. The percentage of non-dippers (BP nocturnal decline ⬍10% with respect to the diurnal BP mean) and the percentage of patients with BP in the normotensive range were evaluated as a function of type of medication and circadian time of therapy. As compared to the reported incidence of dippers among untreated hypertensive patients (62% [Hermida et al. Am J Hypertens. 2001;14:33]), the percentage of dippers in this trial was above 50% only on those receiving ARBs (58%), ACE inhibitors (52%) and ␣-blockers (51%). When analysis was restricted to patients with only one morning dose, the percentage of dippers was maintained only on theARB group (57%), and was highly reduced on the other groups (41%, 37%, 39%, 40%, and 28% for CCBs, ACE inhibitors, ␣-blockers, -blockers, and diuretics, respectively). The percentage of patients with controlled ambulatory BP was below 15% in all groups, except for those receiving ARBs (22%). Monotherapy with one morning dose does not preserve the dipping BP pattern, except, at least in some degree, in those patients receiving ARBs. A single morning dose of ACE inhibitors, ␣-blockers, -blockers or diuretics shows a poor nocturnal BP control, what seems to be related to their therapeutic coverage shorter than 24 hours.
POSTERS: Antihypertensive Drugs
39A
incidence of drug-related AEs was similar among the treatment groups (L100/25 7.5%, L50/12.5 7.1%, and PBO 11.2%). Losartan 100 mg/HCTZ 25 mg provided additional antihypertensive efficacy beyond that of losartan 50 mg/HCTZ 12.5 mg (and both are superior to placebo) as measured by change from baseline in mean trough SiDBP after 8 weeks of therapy. Nearly 9 out of 10 patients treated with losartan 100 mg/HCTZ 25 mg responded to therapy, as did approximately 4 out of 5 patients treated with losartan 50 mg/HCTZ 12.5 mg. The tolerability profiles of the losartan treatment arms were similar to that of placebo.
SiDBP (mm Hg) L100/25
L50/12.5
SiSBP (mm Hg) PBO L100/25
L50/12.5
PBO
Baseline (BSL) 107.9 108.0 108.2 159.9 160.5 161.1 Change from ⫺17.5**,*** ⫺15.2*** ⫺8.5 ⫺21.8*,*** ⫺18.3*** ⫺4.7 BSL, Week 8 % Responders 86.7*** 78.9*** 50.0 NA NA NA * p ⬍ 0.05 L100/25 vs. L50/12.5. ** p ⬍ 0.01 L100/25 vs. L50/12.5. *** p ⬍ 0.001 L100/25 vs. PBO, and L50/12.5 vs. PBO.
Key Words: Hypertension, Losartan, Angiotensin II Receptor Antagonist
SUPPORT: DGES, PM98-0106; PGICT00-PXI-32205PN; University of Vigo. Key Words: Ambulatory Blood Pressure Monitoring, Monotherapy, Therapeutic Coverage
P-17 LOSARTAN 100 MG/HYDROCHLOROTHIAZIDE 25 MG IS EFFECTIVE AND WELL TOLERATED IN THE TREATMENT OF MODERATE-TO-SEVERE ESSENTIAL HYPERTENSION Alan H. Gradman, William E. Brady, Lisa P. Gazdick, Kevin J. Gergich, Paulette A. Lyle, Robert K. Zeldin. The Western Pennsylvania Hospital, Pittsburgh, PA; Merck & Co., Inc., Whitehouse Station, NJ. Previous studies indicate that most patients with moderate-to-severe hypertension (HTN) require multiple drugs to achieve goal blood pressure (BP). The objective of this study was to compare the antihypertensive efficacy and tolerability over 8 weeks of losartan potassium 100 mg/hydrochlorothiazide 25 mg (L100/25) vs. losartan potassium 50 mg/hydrochlorothiazide 12.5 mg (L50/12.5) vs. placebo (PBO) in patients with moderate-to-severe essential HTN (diastolic BP [DBP] 105115 mm Hg). The primary efficacy measurement was the mean change from baseline (BSL) in trough sitting DBP (SiDBP) in L100/25 vs. L50/12.5. This was a randomized, double-blind, multicenter, parallel-group study. After a 4-week placebo run-in period, 446 patients were randomized to receive L100/25 (n⫽173) or L50/12.5 (n⫽184) or PBO (n⫽89) once daily for 8 weeks. Of these, 430 patients (L100/25 [n⫽166], L50/12.5 [n⫽180], and PBO [n⫽84]) had BSL and post-BSL assessments of SiDBP. BP measurements were taken at trough, 22-26 hours after the last dose, following AHA guidelines. Changes from BSL to Week 8 were analyzed using an ANCOVA model with terms for treatment, site, and BSL value. Responders were defined as patients with mean trough SIDBP ⬍90 mm Hg or ⱖ10 mm Hg decrease in mean trough SiDBP. Percentage of responders was analyzed using a logistic regression model with a term for treatment. The incidence of any adverse events (AEs) was similar between the L100/25 (34.7%) and PBO (32.6%) groups, while it was lower in the L50/12.5 group (23.9%). The
P-18 COMPARATIVE EFFECTS OF LERCANIDIPINE AND HYDROCHLOROTHIAZIDE ON HYPERTENSIONRELATED CARDIAC AND VASCULAR STRUCTURAL ALTERATIONS Gino Seravalle, Maria L. Stella, Guido Grassi, Giuseppe Mancia. Cardiology, Istituto Auxologico Italiano - S.Luca Hpt, Milan, Italy; Clinica Medica, S.Gerardo Hpt, Monza (MI), Italy. Objective: To evaluate the effects of a new calcium antagonist, lercanidipine (L), versus hydrochlorothiazide (H) on cardiac and vascular structural alterations associated to hypertension. Methods: In 24 untreated essential hypertensives (EH, age 47.3⫾0.5 yrs, mean arterial pressure MAP 115.4⫾3.6 mmHg), we measured beatto-beat MAP (Finapres), heart rate (HR, EKG), forearm and calf blood flow (FBF, CBF venous occlusion pletysmography) and calculated forearm and calf vascular resistance at rest (FVR and CVR) and following 12 min of local ischaemia associated with 2 min of isometric exercise (FVR min ,CVR min). Measurements also included echocardiographic assessment of left ventricular mass index (LVMI). The protocol, performed in the no drug condition, was repeated following 6 and 12 month treatment with L (10 mg/day, n⫽12) or H (25 mg/day, n⫽12) according to a double-blind randomized design. Results: After 6 months, treatment with L and H caused superimposable reductions in MAP (-12.9⫾1.1 vs -10.8⫾1.4 mmHg, p⬍0.01 for both) and LVMI (-9.5⫾2.0 vs -9.1⫾1.8 %, p⬍0.05) without affecting HR values. In contrast the reduction in FVRmin and CVRmin was significantly greater for L than H (-29.4⫾ 3 vs -7.8⫾1.5% and -21.1⫾ 2 vs -4.3⫾0.9%, p⬍0.01).This was the case also after 12 months of treatment, the LVMI reduction being superimposable in the 2 groups while the FVRmin and CVRmin reductions being more than 50% greater in the L-treated than in H-treated group. Conclusions: These data provide evidence that 1) therapeutical regression of cardiac and vascular hypertrophy have a similar temporal profile and 2) L is superior to H in favouring the regression of vascular hypertrophy Key Words: Regression of Vascular and Cardiac Hypertrophy, Antihypertensive Drugs, Vascular Structural Alterations
medication and time of treatment in patients receiving only one drug. We studied 275 patients with mild-moderate essential hypertension (115 men), 53.2⫾14.1 (mean⫾SD) years of age, who underwent antihypertensive treatment in monotherapy for at least 3 months. BP was measured at 20-minute intervals during the day (07:00 to 23:00 hours) and every 30-minutes at night for 48 consecutive hours. Physical activity was simultaneously monitored at 1-minute intervals by wrist actigraphy. The percentage of non-dippers (BP nocturnal decline ⬍10% with respect to the diurnal BP mean) and the percentage of patients with BP in the normotensive range were evaluated as a function of type of medication and circadian time of therapy. As compared to the reported incidence of dippers among untreated hypertensive patients (62% [Hermida et al. Am J Hypertens. 2001;14:33]), the percentage of dippers in this trial was above 50% only on those receiving ARBs (58%), ACE inhibitors (52%) and ␣-blockers (51%). When analysis was restricted to patients with only one morning dose, the percentage of dippers was maintained only on theARB group (57%), and was highly reduced on the other groups (41%, 37%, 39%, 40%, and 28% for CCBs, ACE inhibitors, ␣-blockers, -blockers, and diuretics, respectively). The percentage of patients with controlled ambulatory BP was below 15% in all groups, except for those receiving ARBs (22%). Monotherapy with one morning dose does not preserve the dipping BP pattern, except, at least in some degree, in those patients receiving ARBs. A single morning dose of ACE inhibitors, ␣-blockers, -blockers or diuretics shows a poor nocturnal BP control, what seems to be related to their therapeutic coverage shorter than 24 hours.
POSTERS: Antihypertensive Drugs
39A
incidence of drug-related AEs was similar among the treatment groups (L100/25 7.5%, L50/12.5 7.1%, and PBO 11.2%). Losartan 100 mg/HCTZ 25 mg provided additional antihypertensive efficacy beyond that of losartan 50 mg/HCTZ 12.5 mg (and both are superior to placebo) as measured by change from baseline in mean trough SiDBP after 8 weeks of therapy. Nearly 9 out of 10 patients treated with losartan 100 mg/HCTZ 25 mg responded to therapy, as did approximately 4 out of 5 patients treated with losartan 50 mg/HCTZ 12.5 mg. The tolerability profiles of the losartan treatment arms were similar to that of placebo.
SiDBP (mm Hg) L100/25
L50/12.5
SiSBP (mm Hg) PBO L100/25
L50/12.5
PBO
Baseline (BSL) 107.9 108.0 108.2 159.9 160.5 161.1 Change from ⫺17.5**,*** ⫺15.2*** ⫺8.5 ⫺21.8*,*** ⫺18.3*** ⫺4.7 BSL, Week 8 % Responders 86.7*** 78.9*** 50.0 NA NA NA * p ⬍ 0.05 L100/25 vs. L50/12.5. ** p ⬍ 0.01 L100/25 vs. L50/12.5. *** p ⬍ 0.001 L100/25 vs. PBO, and L50/12.5 vs. PBO.
Key Words: Hypertension, Losartan, Angiotensin II Receptor Antagonist
SUPPORT: DGES, PM98-0106; PGICT00-PXI-32205PN; University of Vigo. Key Words: Ambulatory Blood Pressure Monitoring, Monotherapy, Therapeutic Coverage
P-17 LOSARTAN 100 MG/HYDROCHLOROTHIAZIDE 25 MG IS EFFECTIVE AND WELL TOLERATED IN THE TREATMENT OF MODERATE-TO-SEVERE ESSENTIAL HYPERTENSION Alan H. Gradman, William E. Brady, Lisa P. Gazdick, Kevin J. Gergich, Paulette A. Lyle, Robert K. Zeldin. The Western Pennsylvania Hospital, Pittsburgh, PA; Merck & Co., Inc., Whitehouse Station, NJ. Previous studies indicate that most patients with moderate-to-severe hypertension (HTN) require multiple drugs to achieve goal blood pressure (BP). The objective of this study was to compare the antihypertensive efficacy and tolerability over 8 weeks of losartan potassium 100 mg/hydrochlorothiazide 25 mg (L100/25) vs. losartan potassium 50 mg/hydrochlorothiazide 12.5 mg (L50/12.5) vs. placebo (PBO) in patients with moderate-to-severe essential HTN (diastolic BP [DBP] 105115 mm Hg). The primary efficacy measurement was the mean change from baseline (BSL) in trough sitting DBP (SiDBP) in L100/25 vs. L50/12.5. This was a randomized, double-blind, multicenter, parallel-group study. After a 4-week placebo run-in period, 446 patients were randomized to receive L100/25 (n⫽173) or L50/12.5 (n⫽184) or PBO (n⫽89) once daily for 8 weeks. Of these, 430 patients (L100/25 [n⫽166], L50/12.5 [n⫽180], and PBO [n⫽84]) had BSL and post-BSL assessments of SiDBP. BP measurements were taken at trough, 22-26 hours after the last dose, following AHA guidelines. Changes from BSL to Week 8 were analyzed using an ANCOVA model with terms for treatment, site, and BSL value. Responders were defined as patients with mean trough SIDBP ⬍90 mm Hg or ⱖ10 mm Hg decrease in mean trough SiDBP. Percentage of responders was analyzed using a logistic regression model with a term for treatment. The incidence of any adverse events (AEs) was similar between the L100/25 (34.7%) and PBO (32.6%) groups, while it was lower in the L50/12.5 group (23.9%). The
P-18 COMPARATIVE EFFECTS OF LERCANIDIPINE AND HYDROCHLOROTHIAZIDE ON HYPERTENSIONRELATED CARDIAC AND VASCULAR STRUCTURAL ALTERATIONS Gino Seravalle, Maria L. Stella, Guido Grassi, Giuseppe Mancia. Cardiology, Istituto Auxologico Italiano - S.Luca Hpt, Milan, Italy; Clinica Medica, S.Gerardo Hpt, Monza (MI), Italy. Objective: To evaluate the effects of a new calcium antagonist, lercanidipine (L), versus hydrochlorothiazide (H) on cardiac and vascular structural alterations associated to hypertension. Methods: In 24 untreated essential hypertensives (EH, age 47.3⫾0.5 yrs, mean arterial pressure MAP 115.4⫾3.6 mmHg), we measured beatto-beat MAP (Finapres), heart rate (HR, EKG), forearm and calf blood flow (FBF, CBF venous occlusion pletysmography) and calculated forearm and calf vascular resistance at rest (FVR and CVR) and following 12 min of local ischaemia associated with 2 min of isometric exercise (FVR min ,CVR min). Measurements also included echocardiographic assessment of left ventricular mass index (LVMI). The protocol, performed in the no drug condition, was repeated following 6 and 12 month treatment with L (10 mg/day, n⫽12) or H (25 mg/day, n⫽12) according to a double-blind randomized design. Results: After 6 months, treatment with L and H caused superimposable reductions in MAP (-12.9⫾1.1 vs -10.8⫾1.4 mmHg, p⬍0.01 for both) and LVMI (-9.5⫾2.0 vs -9.1⫾1.8 %, p⬍0.05) without affecting HR values. In contrast the reduction in FVRmin and CVRmin was significantly greater for L than H (-29.4⫾ 3 vs -7.8⫾1.5% and -21.1⫾ 2 vs -4.3⫾0.9%, p⬍0.01).This was the case also after 12 months of treatment, the LVMI reduction being superimposable in the 2 groups while the FVRmin and CVRmin reductions being more than 50% greater in the L-treated than in H-treated group. Conclusions: These data provide evidence that 1) therapeutical regression of cardiac and vascular hypertrophy have a similar temporal profile and 2) L is superior to H in favouring the regression of vascular hypertrophy Key Words: Regression of Vascular and Cardiac Hypertrophy, Antihypertensive Drugs, Vascular Structural Alterations