Hemodynamic interactions between diuretics and calcium antagonists in the treatment of hypertensive patients
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 amiloride 5 mg (HA), and then after felodipine 5 mg twice daily (F) or felodipine ER 10 mg daily (FER) (double-blind 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. cm5, 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 by diuretic treatment.