Effects of antihypertensive drugs on SBP variability are dose-dependent and persist when used in combinations .
Use of a high dose of a calcium channel blocker alone or in combination with other agents is therefore likely to be particularly effective in prevention of stroke
BACKGROUND AND PURPOSE Recent studies have shown that visit-to-visit blood pressure variability is a powerful risk factor for stroke , is reduced by calcium channel blockers and diuretics , and increased by β-blockers .
However , it is unknown whether these effects are dose-dependent and persist in combination with other drugs .
Felodipine in hypertensive patients. A dose finding study in patients refractory to beta-blocker monotherapy.
In a double-blind study , 128 patients with essential hypertension , refractory to beta-blocker monotherapy , were r and omised to 1 of 4 treatment groups . Felodipine 2.5 mg twice daily , 5 mg twice daily , 10 mg twice daily or matched placebo twice daily were administered in addition to the beta-blocker for 4 weeks . Mean supine blood pressure before r and omisation to treatment was 167/104 + /- 20/7 mm Hg . After 4 weeks of treatment , supine blood pressures 2 hours after dose were 161/98 + /- 20/10 mm Hg ( P ) , 152/92 + /- 23/8 mm Hg ( felodipine 2.5 mg ) , 142/87 + /- 18/7 mm Hg ( felodipine 5 mg ) and 142/86 + /- 17/7 mm Hg ( felodipine 10 mg ) . The falls in systolic and diastolic blood pressures were significantly greater for all 3 felodipine groups than for placebo .  Blood pressure reductions were less marked 14 hours after dosage : 161/100 + /- 20/9 mm Hg ( P ) , 160/97 + /- 24/9 mm Hg ( felodipine 2.5 mg ) , 153/97 + /- 21/11 mm Hg ( felodipine 5 mg ) , and 157/94 + /- 19/9 mm Hg ( felodipine 10 mg ) ; but the two higher doses of felodipine produced a significantly greater sustained fall in blood pressure than placebo . There was a correlation between the dose of felodipine and its antihypertensive effect . St and ing blood pressures were reduced to the same extent as supine measurements . Heart rate was not significantly affected . Bodyweight did not increase during the study . Side effects of felodipine therapy were minor , and mostly attributable to the vasodilatory properties of the drug . Only 4 patients withdrew because of side effects . It is concluded that felodipine is an effective and well tolerated antihypertensive drug , and that 5 mg twice daily is a suitable starting dose in hypertensive patients refractory to beta-blocker monotherapy . It may be necessary to increase this dose to 10 mg twice daily in selected patients
Effects of antihypertensive drugs on SBP variability are dose-dependent and persist when used in combinations .
Use of a high dose of a calcium channel blocker alone or in combination with other agents is therefore likely to be particularly effective in prevention of stroke
BACKGROUND AND PURPOSE Recent studies have shown that visit-to-visit blood pressure variability is a powerful risk factor for stroke , is reduced by calcium channel blockers and diuretics , and increased by β-blockers .
However , it is unknown whether these effects are dose-dependent and persist in combination with other drugs .