Hemodynamic interactions between diuretics and calcium antagonists in the treatment of hypertensive patients (original) (raw)

1990, Cardiovascular Drugs and Therapy

To investigate the hypotensive and hemodynamic effects of plain and extended-release (ER) formulations of felodipine added to a diuretic in the treatment of moderate essential hypertension, we studied 18 patients in a randomized, double-blind, cross-over study. Blood pressure (BP), heart rate (HR), hemodynamics (bioimpedance), foot volume (Archimedes' principle), and symptoms were evaluated after a 1-month placebo washout, after 1-month's treatment with a fixed combination of hydrochlorothiazide 50 mg plus amiioride 5 mg (HA), and then after felodipine 5 mg twice daily (F) or felodipine ER 10 mg daily (FER) (doubleblind phase), each given for 2 weeks in a randomized sequence together with the diuretic. All measurements were performed at the end of the dosing interval. At baseline, supine SBP/DBP was 175.6 _+ 12.9/113.4 • 8.1 mmHg; HR was 77.3 +_ 7.0 beats/min; CO was 5.3 -+ 1.4 l/min; SVR was 2166 _~ 707 dynes sec. em ', and'foot volume was 433 ~ 195 ml (FV). HA induced a reduction (p < 0.05) in BP; one patient had a DBP = 90 mmHg and was excluded from the combination study; eight patients had a DBP reduction of >-10 mmHg (responders), and their blood pressure was mainly reduced by a fall in SVR. HR, CO, and FV were unchanged. The addition of felodipine to a diuretic induced a further significant (p < 0.001) reduction in BP with respect to HA alone, with no differences between F and FER. All patients had a DBP fall > 10 mmHg, which had no relationship to their response to the diuretic. The antihypertensive effect of felodipine was due to a reduction in SVR (p < 0.05). CO and HR were significantly (p > 0.05) increased by felodipine added to HA. FV was increased by felodipine. During felodipine treatment, side effects were significantly decreased in comparison with placebo. Thus, a once-daily administration of 10 mg extended-release felodipine was equieffective with felodipine 5 mg twice daily in hypertensives who were sufficiently controlled by diuretic alone. The antihypertensive effect of felodipine is due to a reduction in SVR and is not prevented hv diuretic treatment_