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 .
Controlled trial of losartan given concomitantly with different doses of hydrochlorothiazide in hypertensive patients.
The purpose of this trial was to evaluate the antihypertensive efficacy of the concomitant administration of selected doses of hydrochlorothiazide ( HCTZ ) on a background of losartan potassium ( losartan ) 50 mg , a selective angiotensin II receptor antagonist . Patients with essential hypertension ( > or = 95 mmHg inclusion criteria ) with a mean sitting diastolic blood pressure ( SiDBP ) of 105 + /- 0.4 ( S.E. ) mmHg entered a 4-week , single-blind monotherapy period of losartan 50 mg once daily . At the end of the monotherapy period , patients whose blood pressure was adequately controlled were discontinued . Patients whose blood pressure was partially controlled based on a SiDBP > 92 mmHg entered a 12 week double-blind period and were r and omly assigned to either receive placebo ( n = 80 ) , HCTZ 6.25 mg ( n = 80 ) , HCTZ 12.5 mg ( n = 72 ) or HCTZ 25 mg ( n = 80 ) in addition to losartan 50 mg . During the losartan monotherapy period , there was a 4 mmHg fall in SiDBP with a further fall of 5 mmHg after 12 weeks of double-blind therapy in the losartan/placebo control group . Based on the between group differences in BP change from the end of the losartan monotherapy period ( baseline ) to end of 12 weeks of double-blind , the concomitant administration of a very low dose of HCTZ ( 6.25 mg ) with losartan did not significantly decrease SiDBP compared with the fall in blood pressure in the losartan/placebo control group ( diff . between groups = -2 ( 95 % C.I.[-4.1 , + 0.9 ] mmHg ) ) . However , the concomitant administration of HCTZ 12.5 or 25 mg with losartan 50 mg result ed in significantly different ( p < or = 0.05 ) reductions in diastolic blood pressure compared to the losartan/placebo group ( diff . between groups = -4 ( 95 % C.I. [ -6.3 , -1.1 ] mmHg ) for 12.5 mg combination group ; -6 ( 95 % C.I. [ -8.3 , -3.3 ] ) mmHg for the HCTZ 25 mg combination group ) . The proportions of patients treated with losartan plus HCTZ 12.5 mg or 25 mg that achieved a trough SiDBP < 88 mmHg or a trough SiDBP > or = 88 mmHg but with a decrease of at least 5 mmHg were 71 % and 83 % , respectively . The percentage of clinical adverse experiences that were considered drug-related as assessed by the investigator were generally similar across all treatment groups . There were no reports of orthostatic hypotension in any of the treatment groups . Changes in serum glucose , potassium and uric acid were not appreciably different amongst the treatment groups . In summary , in patients with predominantly moderate to severe essential hypertension , the addition of HCTZ 12.5 mg or 25 mg to losartan 50 mg produced effective control of blood pressure in a substantial majority of patients who only partially responded to losartan monotherapy . There were no differences amongst the treatment groups with respect to drug-related adverse experiences in this trial
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 .