Background: Dependent leg edema complicates treatment with amlodipine (AMLO) and other dihydropiridine (DHP) calcium channel blocker (CCB)s and frequently obliges to interrupt an otherwise highly effective therapeutic regimen. Among other possible explanations, DHP CCBs may alter the balance between pre- and post-capillary pressures by dilating preferentially precapillary arterioles of the cutaneous microcirculation, thus increasing capillary pressure and promoting fluid extravasation. In contrast, DHP CCBs such as lercanidipine (LERCA), which may relax both pre- and post-capillary vessels in in-vitro studies, may induce a lesser degree of dependent edema. However, this hypothesis has never been tested in man. Methods: We compared the leg edema-forming potential of AMLO and LERCA according to a cross-over, sequence-randomized experimental design carried out in 22 never treated mild-moderate uncomplicated essential hypertensive (EH) males (age: 48±5 yrs). Drugs were administered at doses (AMLO: 10 vs LERCA: 20 mg o.d.) equipotent on the basis of published titration studies. Active treatment was given for 2 weeks preceded and followed by 2 week wash-outs to allow the recovery of study variables to baseline. Leg weight (LW) was used as a surrogate measure of dependent edema; the parameter was measured by water plethysmography (accuracy within 5 grams; variation coefficient: 0.8%) at both legs and the data were averaged. Systolic and diastolic blood pressure (BP, the mean of at least 10 determinations) was recorded by an automated oscillometric device. Results: (means±SD): AMLO (from 147±8/94±12 to 137±14/83±9 mmHg, p<.002) and LERCA (from 145±18/92±12 to 137±9/83±8 mmHg, p<0.01) decreased BP to a similar extent. Both drugs increased LW (AMLO: from 3244±306 to 3324±293 grams, p<0.001; LERCA: from 3256±279 to 3293±258 grams, p<0.04), but the increase was greater during AMLO (80±91 vs 37±74 grams, p<0.03). Conclusions: These data, consistent with pharmacological differences previously reported at the in-vitro microvascular level, show for the first time in man that, for a similar drop in BP, the edema-forming potential of AMLO and LERCA, two CCBs belonging to the same DHP class, is not equivalent.

P-60: Dihydropiridine calcium channel blockers and dependent edema: a comparison between amlodipine and lercanidipine in essential hypertensive patients

DELL'OMO, GIULIA;BALBARINI, ALBERTO;
2002

Abstract

Background: Dependent leg edema complicates treatment with amlodipine (AMLO) and other dihydropiridine (DHP) calcium channel blocker (CCB)s and frequently obliges to interrupt an otherwise highly effective therapeutic regimen. Among other possible explanations, DHP CCBs may alter the balance between pre- and post-capillary pressures by dilating preferentially precapillary arterioles of the cutaneous microcirculation, thus increasing capillary pressure and promoting fluid extravasation. In contrast, DHP CCBs such as lercanidipine (LERCA), which may relax both pre- and post-capillary vessels in in-vitro studies, may induce a lesser degree of dependent edema. However, this hypothesis has never been tested in man. Methods: We compared the leg edema-forming potential of AMLO and LERCA according to a cross-over, sequence-randomized experimental design carried out in 22 never treated mild-moderate uncomplicated essential hypertensive (EH) males (age: 48±5 yrs). Drugs were administered at doses (AMLO: 10 vs LERCA: 20 mg o.d.) equipotent on the basis of published titration studies. Active treatment was given for 2 weeks preceded and followed by 2 week wash-outs to allow the recovery of study variables to baseline. Leg weight (LW) was used as a surrogate measure of dependent edema; the parameter was measured by water plethysmography (accuracy within 5 grams; variation coefficient: 0.8%) at both legs and the data were averaged. Systolic and diastolic blood pressure (BP, the mean of at least 10 determinations) was recorded by an automated oscillometric device. Results: (means±SD): AMLO (from 147±8/94±12 to 137±14/83±9 mmHg, p<.002) and LERCA (from 145±18/92±12 to 137±9/83±8 mmHg, p<0.01) decreased BP to a similar extent. Both drugs increased LW (AMLO: from 3244±306 to 3324±293 grams, p<0.001; LERCA: from 3256±279 to 3293±258 grams, p<0.04), but the increase was greater during AMLO (80±91 vs 37±74 grams, p<0.03). Conclusions: These data, consistent with pharmacological differences previously reported at the in-vitro microvascular level, show for the first time in man that, for a similar drop in BP, the edema-forming potential of AMLO and LERCA, two CCBs belonging to the same DHP class, is not equivalent.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/70202
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