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 .
Evaluation of blood pressure response to the combination of enalapril (single dose) and diltiazem ER (four different doses) in systemic hypertension.
Angiotensin-converting enzyme inhibitors and calcium antagonists are 2 classes of antihypertensive agents frequently used either as monotherapy or in combination . A 6-week , multicenter , r and omized , double-blind , placebo-controlled trial was conducted in essential hypertensive patients ( diastolic blood pressures [ BP ] when seated , 95 - 115 mm Hg ) to evaluate the efficacy , dose response , and safety profiles of enalapril combined with a new once-daily formulation of diltiazem .  BP and heart rate were measured at 5 ( peak ) and 24 ( trough ) hours after dose to assess the efficacy and pharmacodynamic profile of the combination given once daily . There were 336 patients r and omly assigned to either enalapril 5 mg plus 1 of 4 dose levels of diltiazem ER ( 60 , 120 , 180 , or 240 mg ) , enalapril 5 mg alone , or placebo . Each combination dose level produced statistically significant reductions ( p < 0.05 ) in trough diastolic BP when seated , compared with placebo ( -6.8 , -8.3 , -10.1 , and -10.3 mm Hg for the diltiazem ER doses of 60 , 120 , 180 , and 240 mg , respectively ) . The 3 highest combination dose levels result ed in statistically significant ( p < 0.05 ) decreases in trough diastolic BP when seated , compared with placebo . There was a significant ( p < 0.001 ) linear dose-response relation . A trough-to-peak ratio > or = 0.5 was shown for the 3 highest combination doses . Drug-related adverse events were seen in 8.9 % to 19 % of the combination patients , 14.3 % of the enalapril patients , and 8.6 % of the placebo patients . The frequency and type of adverse events were those currently noted with each drug studied when used as monotherapy
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 .