Objective: To compare the efficacy and tolerability of felodipine extended release (ER) 2.5 mg (F2.5) and 5 mg (F5) once daily with nifedipine Retard 10 mg (N20) and 20 mg (N40) twice daily as additional therapy in patients who remained hypertensive despite treatment with an ACE-inhibitor, beta-blocker or diuretic.
Design and methods: In a multicentre, double-blind parallel study, 61 men and 54 women, aged 35-75, with a supine diastolic blood pressure between 95 and 115 mmHg were randomised to treatment with F2.5, F5, N20 or N40 for 8 weeks, with optional doubling of the dose after 4 weeks. Blood pressure was measured at the office after 0, 4 and 8 weeks and by 24-h ambulatory monitoring (ABPM) after 0 and 4 weeks. Spontaneously reported adverse events and a subjective symptom assessment questionnaire were used for side-effect profiling.
Results: Mean office systolic/diastolic blood pressure was clinically relevantly reduced in all treatment groups after 4 weeks by 8/7, 12/9, 11/9 and 18/11 mmHg for F2.5, F5, N20 and N40, respectively, and after 8 weeks (F2.5-5: 17/11 mmHg: F5-10: 18/14 mmHg; N20-40: 19/14 mmHg; N40-80: 25/14 mmHg) with no statistically significant differences between these groups. The lowest dose of felodipine (F2.5) was the least effective. After 4 weeks the ABPM showed consistent 24-h reductions in blood pressure (4/2; 8/5; 7/5; 10/6 mmHg, respectively) over 24 h for the felodipine ER 5 mg group only and for both nifedipine groups. No statistically significant difference between these groups was found. An office responder does not appear to be identical to an ambulatory one and vice versa. The adverse events, mostly oedema, flushing and headache, were dose-related.
Conclusions: Both felodipine ER and nifedipine Retard are effective "add-on' drugs in patients with monotherapy-resistant hypertension. The blood-pressure-lowering effect is dose-dependent and tolerability is inversely related to efficacy. The results emphasize the benefits of combining two agents with low doses.