- Email: [email protected]
Comparison between irbesartan and amlodipine in reducing left ventricular mass in hypertensive patients with left ventricular hypertrophy
AJH–April 2002–VOL. 15, NO. 4, PART 2
POSTERS: Antihypertensive Drugs
P-56 CANDESARTAN CILEXITIL BOTH ALONE AND COMBINED TO HYDROCHLOROTHIAZIDE HAS NO EFFECT ON METABOLIC PARAMETERS IN HYPERTENSIVE PATIENTS Mari Auranen, Petri Ma¨ kela¨ , Ilkka Kantola. Department of Medicine, Turku University Central Hospital, Turku, Finland. As a part of the Finnish Hypertension Measurement Study we studied the effect of candesartan cilexitil and its combination to hydrochlorothiazide (HCTZ) on plasma glucose and serum lipid concentrations. After a four week placebo wash-out period 38 patients whose mean daytime 24 hour ABPM DBP was ⬎85 mmHg were given candesartan cilexitil (Atacand, AstraZeneca) 8 mg a day for six weeks. After that time the dose was increased to 16 mg a day if DBP was not ⬍80 mmHg. At 12 weeks HCTZ 12,5 mg a day was combined to candesartan if DBP goal was not achieved (n⫽18). Thereafter medication was continued unchanged up to 24 weeks. Table 1.The effect of 12 week candesartan (either 8 mg or 16 mg a day alone) treatment on plasma glucose and serum lipid concentrations (n⫽38).The combination of HCTZ 12.5 mg a day to candesartan (either 8 mg or 16 mg a day ) (n⫽18) did not worsen the metabolic parameters. Plasma glucose concentration was at 12 weeks 5.37 (0.44) mmol/l and at 24 weeks 5.39 (0.53) mmol/l. Total cholesterol was 5.82 (1.03) mmol/l at 12 weeks and 5.70 (0.90) mmol/l at 24 weeks, fS-HDL-chol was 1.47 (0.40) mmol/l and 1.45 (0.36) mmol/l, fS-trigly 1.18 (0.49) mmol/l and 1.21 (0.52) mmol/l and fS-LDL-chol 3.82 (0.83) and 3.71 (0.69) mmol/l. Candesartan cilexitil both alone and combined to hydrochlorothiazide was metabolically neutral in Finnish hypertensive patient. 0 week
fP-gluc (mmol/l) fS-chol (mmol/l) fS-HDL-chol (mmol/l) fS-trigly (mmol/l) fS-LDL-chol (mmol/l)
12 weeks
mean
SD
mean
SD
5.51 5.74 1.50 1.21 3.67
0.63 0.89 0.46 0.53 0.75
5.48 5.71 1.49 1.27 3.65
0.59 0.90 0.45 0.63 0.73
Key Words: Metabolism, Candesartan Cilexitil, Hypertension
P-57 COMPARISON OF THE EFFECT OF SUSTAINEDRELEASE ISRADIPINE AND FELODIPINE IN HYPERTENSIVE MEN Michael B. Ganz, B. Saksa. Case Western Reserve University School of Medicine, Cleveland, OH, United States. Both sustained-release felodipine (SR-F) and isradipine (SR-I) provide effective control of hypertension with once per day dosing, but the pharmacodynamics of SR-I (trough/peak ⬇ 76%-100%) suggest that it might provide better 24-hour control than SR-F (trough/peak ⬇ 50%). We tested this hypothesis in an open-label, drug substitution study. A total of 41 male patients who had been treated with SR-F for at least 6 months were enrolled in the study. The only major exclusion criteria were evidence of coronary artery disease or congestive heart failure. The average age was 63 years, 90% were receiving adjuvant therapy to control blood pressure (1 additional drug - 49%, 2 additional drugs 41%), and 61% were controlled (BP ⱕ 140/90) on their current regimen. Treatment regimen remained constant during the 6 months prior to entering the study. All BP measurements were made 24 hr after the previous dose. Seated BP was measured 3 times during this 6-month period and again 2 weeks prior to switching drugs. Baseline BP was the average of these 4 measurements. SR-I was substituted for SR-F on a mg-for-mg basis and BP was measured 2, 4, and 6 weeks after switching drugs. After 6 weeks the patients were returned to SR-F and BP was
53A
measured 6 weeks later. SBP was significantly lower in the SR-I 10 mg group after 4 weeks and remained lower through 6 weeks. DBP was also reduced, but the change was not significant. Nine additional patients were adequately controlled while on SR-I, primarily because of reductions in SBP. Six weeks after returning to SR-F, BP had returned towards baseline values. These results indicate that SR-I can be safely substituted for SR-F and suggest that SR-I may provide better 24-hour control of BP than SR-F.mean ⫾ SD, *P⬍.01
Dose
N
5 mg
18
10 mg
23
SBP DBP SBP DBP
Felodipine Baseline
Isradipine 6 Weeks
Felodipine 6 Weeks
151.4 ⫾ 8.9 87.1 ⫾ 6.8 156.1 ⫾ 10.2 86.2 ⫾ 8.0
147.2 ⫾ 9.1 84.7 ⫾ 8.3 145.3 ⫾ 8.0* 82.6 ⫾ 6.7
150.4 ⫾ 10.7 86.5 ⫾ 6.9 150.1 ⫾ 10.2 85.2 ⫾ 7.3
Key Words: Calcium Channel Blocker, Isradipine, Felodipine
P-58 COMPARISON BETWEEN IRBESARTAN AND AMLODIPINE IN REDUCING LEFT VENTRICULAR MASS IN HYPERTENSIVE PATIENTS WITH LEFT VENTRICULAR HYPERTROPHY Carlo Gaudio, Fabio M. Ferri, Sara Di Michele, Alessandro Vittore, Giuseppe Pannarale. II Department of Cardiology, ‘La Sapienza’ University, Rome, Italy. The aim of this between-patient, open-label, blind observer, randomized study was to assess the effects of irbesartan and amlodipine monotherapies on left ventricular mass index (LVMi) in patients with mild-tomoderate untreated essential hypertension and left ventricular hypertrophy (LVH). Sixty hypertensive patients (pts) (35 males, 25 females, mean age 52.8 ⫹ 12.6 years) LVH were randomized to irbesartan (I) 150 mg or amlodipine (A) 5 mg once daily. Dosage of both drugs was increased to I 300 mg or A 10 mg, once daily, in case of seated diastolic blood pressure (SDBP) still ⬎90 mmHg after the first 2 weeks of treatment. After 4 weeks, only responders (SDBP ⬍ 90 mmHg) entered the 5-month maintenance period. At baseline (T0) and after three (T3) and six (T6) months of monotherapy, all pts underwent clinical and echocardiographic (ECHO) evaluation in order to assess the changes in SDBP, LVMi, the interventricular septal (IVS) and left ventricular posterior wall (PW) thickness. The results seen at T6 were already present at T3. Mean values (⫹ SEM) obtained at T0 and T6 were the following: I T0 BP (mmHg) Systolic 160.5 ⫾ 9.2 Diastolic 103 ⫾ 3.4 ECHO LVMi (g/m2) 137.4 ⫾ 14.3 IVS (mm) 12.9 ⫾ 0.8 LVPW (mm) 11.8 ⫾ 0.6 I ⫽ irbesartan; A ⫽ amlodipine;
A T6
T0
T6
135 ⫾ 4.7# 82 ⫾ 2.5#
158.3 ⫾ 11.1 138.8 ⫾ 6.5# 104.4 ⫾ 3.9 85 ⫾ 3.5#
104.9 ⫾ 12.3# 10.8 ⫾ 0.6# 9.9 ⫾ 0.6#
139.8 ⫾ 22.4 126.6 ⫾ 18.3° 12.8 ⫾ 1.0 11.7 ⫾ 0.7* 11.7 ⫾ 1.0 11.1 ⫾ 0.7°
#
p ⬍ 0.001; * p ⬍ 0.01; ° NS vs T0.
In conclusion, despite their similar antihypertensive effects, short-term I led to a greater reduction in LVMi then A monotherapy (23.7% vs 9.5%). Key Words: Irbesartan, Amlodipine, Left Ventricular Hypertrophy
POSTERS: Antihypertensive Drugs
P-56 CANDESARTAN CILEXITIL BOTH ALONE AND COMBINED TO HYDROCHLOROTHIAZIDE HAS NO EFFECT ON METABOLIC PARAMETERS IN HYPERTENSIVE PATIENTS Mari Auranen, Petri Ma¨ kela¨ , Ilkka Kantola. Department of Medicine, Turku University Central Hospital, Turku, Finland. As a part of the Finnish Hypertension Measurement Study we studied the effect of candesartan cilexitil and its combination to hydrochlorothiazide (HCTZ) on plasma glucose and serum lipid concentrations. After a four week placebo wash-out period 38 patients whose mean daytime 24 hour ABPM DBP was ⬎85 mmHg were given candesartan cilexitil (Atacand, AstraZeneca) 8 mg a day for six weeks. After that time the dose was increased to 16 mg a day if DBP was not ⬍80 mmHg. At 12 weeks HCTZ 12,5 mg a day was combined to candesartan if DBP goal was not achieved (n⫽18). Thereafter medication was continued unchanged up to 24 weeks. Table 1.The effect of 12 week candesartan (either 8 mg or 16 mg a day alone) treatment on plasma glucose and serum lipid concentrations (n⫽38).The combination of HCTZ 12.5 mg a day to candesartan (either 8 mg or 16 mg a day ) (n⫽18) did not worsen the metabolic parameters. Plasma glucose concentration was at 12 weeks 5.37 (0.44) mmol/l and at 24 weeks 5.39 (0.53) mmol/l. Total cholesterol was 5.82 (1.03) mmol/l at 12 weeks and 5.70 (0.90) mmol/l at 24 weeks, fS-HDL-chol was 1.47 (0.40) mmol/l and 1.45 (0.36) mmol/l, fS-trigly 1.18 (0.49) mmol/l and 1.21 (0.52) mmol/l and fS-LDL-chol 3.82 (0.83) and 3.71 (0.69) mmol/l. Candesartan cilexitil both alone and combined to hydrochlorothiazide was metabolically neutral in Finnish hypertensive patient. 0 week
fP-gluc (mmol/l) fS-chol (mmol/l) fS-HDL-chol (mmol/l) fS-trigly (mmol/l) fS-LDL-chol (mmol/l)
12 weeks
mean
SD
mean
SD
5.51 5.74 1.50 1.21 3.67
0.63 0.89 0.46 0.53 0.75
5.48 5.71 1.49 1.27 3.65
0.59 0.90 0.45 0.63 0.73
Key Words: Metabolism, Candesartan Cilexitil, Hypertension
P-57 COMPARISON OF THE EFFECT OF SUSTAINEDRELEASE ISRADIPINE AND FELODIPINE IN HYPERTENSIVE MEN Michael B. Ganz, B. Saksa. Case Western Reserve University School of Medicine, Cleveland, OH, United States. Both sustained-release felodipine (SR-F) and isradipine (SR-I) provide effective control of hypertension with once per day dosing, but the pharmacodynamics of SR-I (trough/peak ⬇ 76%-100%) suggest that it might provide better 24-hour control than SR-F (trough/peak ⬇ 50%). We tested this hypothesis in an open-label, drug substitution study. A total of 41 male patients who had been treated with SR-F for at least 6 months were enrolled in the study. The only major exclusion criteria were evidence of coronary artery disease or congestive heart failure. The average age was 63 years, 90% were receiving adjuvant therapy to control blood pressure (1 additional drug - 49%, 2 additional drugs 41%), and 61% were controlled (BP ⱕ 140/90) on their current regimen. Treatment regimen remained constant during the 6 months prior to entering the study. All BP measurements were made 24 hr after the previous dose. Seated BP was measured 3 times during this 6-month period and again 2 weeks prior to switching drugs. Baseline BP was the average of these 4 measurements. SR-I was substituted for SR-F on a mg-for-mg basis and BP was measured 2, 4, and 6 weeks after switching drugs. After 6 weeks the patients were returned to SR-F and BP was
53A
measured 6 weeks later. SBP was significantly lower in the SR-I 10 mg group after 4 weeks and remained lower through 6 weeks. DBP was also reduced, but the change was not significant. Nine additional patients were adequately controlled while on SR-I, primarily because of reductions in SBP. Six weeks after returning to SR-F, BP had returned towards baseline values. These results indicate that SR-I can be safely substituted for SR-F and suggest that SR-I may provide better 24-hour control of BP than SR-F.mean ⫾ SD, *P⬍.01
Dose
N
5 mg
18
10 mg
23
SBP DBP SBP DBP
Felodipine Baseline
Isradipine 6 Weeks
Felodipine 6 Weeks
151.4 ⫾ 8.9 87.1 ⫾ 6.8 156.1 ⫾ 10.2 86.2 ⫾ 8.0
147.2 ⫾ 9.1 84.7 ⫾ 8.3 145.3 ⫾ 8.0* 82.6 ⫾ 6.7
150.4 ⫾ 10.7 86.5 ⫾ 6.9 150.1 ⫾ 10.2 85.2 ⫾ 7.3
Key Words: Calcium Channel Blocker, Isradipine, Felodipine
P-58 COMPARISON BETWEEN IRBESARTAN AND AMLODIPINE IN REDUCING LEFT VENTRICULAR MASS IN HYPERTENSIVE PATIENTS WITH LEFT VENTRICULAR HYPERTROPHY Carlo Gaudio, Fabio M. Ferri, Sara Di Michele, Alessandro Vittore, Giuseppe Pannarale. II Department of Cardiology, ‘La Sapienza’ University, Rome, Italy. The aim of this between-patient, open-label, blind observer, randomized study was to assess the effects of irbesartan and amlodipine monotherapies on left ventricular mass index (LVMi) in patients with mild-tomoderate untreated essential hypertension and left ventricular hypertrophy (LVH). Sixty hypertensive patients (pts) (35 males, 25 females, mean age 52.8 ⫹ 12.6 years) LVH were randomized to irbesartan (I) 150 mg or amlodipine (A) 5 mg once daily. Dosage of both drugs was increased to I 300 mg or A 10 mg, once daily, in case of seated diastolic blood pressure (SDBP) still ⬎90 mmHg after the first 2 weeks of treatment. After 4 weeks, only responders (SDBP ⬍ 90 mmHg) entered the 5-month maintenance period. At baseline (T0) and after three (T3) and six (T6) months of monotherapy, all pts underwent clinical and echocardiographic (ECHO) evaluation in order to assess the changes in SDBP, LVMi, the interventricular septal (IVS) and left ventricular posterior wall (PW) thickness. The results seen at T6 were already present at T3. Mean values (⫹ SEM) obtained at T0 and T6 were the following: I T0 BP (mmHg) Systolic 160.5 ⫾ 9.2 Diastolic 103 ⫾ 3.4 ECHO LVMi (g/m2) 137.4 ⫾ 14.3 IVS (mm) 12.9 ⫾ 0.8 LVPW (mm) 11.8 ⫾ 0.6 I ⫽ irbesartan; A ⫽ amlodipine;
A T6
T0
T6
135 ⫾ 4.7# 82 ⫾ 2.5#
158.3 ⫾ 11.1 138.8 ⫾ 6.5# 104.4 ⫾ 3.9 85 ⫾ 3.5#
104.9 ⫾ 12.3# 10.8 ⫾ 0.6# 9.9 ⫾ 0.6#
139.8 ⫾ 22.4 126.6 ⫾ 18.3° 12.8 ⫾ 1.0 11.7 ⫾ 0.7* 11.7 ⫾ 1.0 11.1 ⫾ 0.7°
#
p ⬍ 0.001; * p ⬍ 0.01; ° NS vs T0.
In conclusion, despite their similar antihypertensive effects, short-term I led to a greater reduction in LVMi then A monotherapy (23.7% vs 9.5%). Key Words: Irbesartan, Amlodipine, Left Ventricular Hypertrophy