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 .
Effects of the angiotensin II receptor blockers telmisartan versus valsartan in combination with hydrochlorothiazide: a large, confirmatory trial
In 2004–2005 , the antihypertensive effects of telmisartan 80 mg versus valsartan 160 mg combined with hydrochlorothiazide 25 mg were assessed in a large placebo-controlled trial in patients with stages 1 and 2 hypertension and demonstrated that both agents were highly effective in lowering blood pressure ( BP ) compared with placebo and that telmisartan lowered BP significantly greater than valsartan . To confirm this finding according to Food and Drug Administration guidelines , we performed a second large trial using the same design in an entirely separate patient population . The trial was double-blind with a 4 : 4 : 1 r and omization scheme to compare once daily telmisartan 80 mg plus hydrochlorothiazide 25 mg versus once daily valsartan 160 mg plus hydrochlorothiazide 25 mg versus once daily placebo on reductions in seated clinic BP in patients with stages 1 and 2 hypertension . The primary endpoints were the changes from baseline in seated diastolic and systolic BP at the end of the 8-week treatment period . Safety endpoints included adverse events , changes in laboratory parameters and pulse rate . In total , 1185 patients were r and omized ( of which 1181 were treated and included in the primary analysis : 528 in the  telmisartan-hydrochlorothiazide  group , 523 in the valsartan-hydrochlorothiazide group , and 130 in the placebo group ) , changes from baseline in BP  following telmisartan-hydrochlorothiazide ( −24.6/−18.2 mmHg ) were significantly greater than both placebo ( −4.1/−6.1 mmHg ) and valsartan-hydrochlorthiazide ( −22.5/−17.0 mmHg ) ( versus placebo , P<0.0001 for systolic and diastolic BP ; versus valsartan-hydrochlorothiazide , P=0.017 for systolic BP and P=0.025 for diastolic BP ) . The total number of patients with at least one adverse event reported was similar among the three treatment groups ( placebo , 42 % , telmisartan-hydrochlorothiazide , 36 % , and valsartan-hydrochlorothiazide , 37 % ) . Thus , this large , second trial confirms that telmisartan-hydrochlorothiazide at doses of 80/25 mg lowered both systolic and diastolic BP to a greater extent than valsartan-hydrochlorothiazide at doses of 160/25 mg in stages 1–2 hypertension . Although these are not the highest doses of these agents at present , at the time that the studies were conducted , they were the maximally approved dosages . Both studies support the strategy of using angiotensin receptor blockers with a higher dose of a thazide diuretic ( 25 mg ) for enhancing the control of hypertension
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 .