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 .
Renal outcomes with different fixed-dose combination therapies in patients with hypertension at high risk for cardiovascular events (ACCOMPLISH): a prespecified secondary analysis of a randomised controlled trial
BACKGROUND The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension ( ACCOMPLISH ) trial showed that initial antihypertensive therapy with benazepril plus amlodipine was superior to benazepril plus hydrochlorothiazide in reducing cardiovascular morbidity and mortality . We assessed the effects of these drug combinations on progression of chronic kidney disease . METHODS ACCOMPLISH was a double-blind , r and omised trial undertaken in five countries ( USA , Sweden , Norway , Denmark , and Finl and ) . 11 506 patients with hypertension who were at high risk for cardiovascular events were r and omly assigned via a central , telephone-based interactive voice response system in a 1:1 ratio to receive benazepril ( 20 mg ) plus amlodipine ( 5 mg ; n=5744 ) or benazepril ( 20 mg ) plus hydrochlorothiazide ( 12.5 mg ; n=5762 ) , orally once daily . Drug doses were force-titrated for patients to attain recommended blood pressure goals . Progression of chronic kidney disease , a prespecified endpoint , was defined as doubling of serum creatinine concentration or end-stage renal disease ( estimated glomerular filtration rate < 15 mL/min/1.73 m(2 ) or need for dialysis ) . Analysis was by intention to treat ( ITT ) . This trial is registered with Clinical Trials.gov , number NCT00170950 . FINDINGS The trial was terminated early ( mean follow-up 2.9 years [ SD 0.4 ] ) because of superior efficacy of benazepril plus amlodipine compared with benazepril plus hydrochlorothiazide . At trial completion , vital status was not known for 143 ( 1 % ) patients who were lost to follow-up ( benazepril plus amlodipine , n=70 ; benazepril plus hydrochlorothiazide , n=73 ) . All r and omised patients were included in the ITT analysis . There were 113 ( 2.0 % ) events of chronic kidney disease progression in the benazepril plus amlodipine group compared with 215 ( 3.7 % ) in the benazepril plus hydrochlorothiazide group ( HR 0.52 , 0.41 - 0.65 , p<0.0001 ) . The most frequent adverse event in patients with chronic kidney disease was peripheral oedema  ( benazepril plus amlodipine , 189 of 561 , 33.7 % ; benazepril plus hydrochlorothiazide , 85 of 532 , 16.0 % ) . In patients with chronic kidney disease , angio-oedema was more frequent in the benazepril plus amlodipine group than in the benazepril plus hydrochlorothiazide group . In patients without chronic kidney disease , dizziness , hypokalaemia , and hypotension were more frequent in the benazepril plus hydrochlorothiazide group than in the benazepril plus amlodipine group . INTERPRETATION Initial antihypertensive treatment with benazepril plus amlodipine should be considered in preference to benazepril plus hydrochlorothiazide since it slows progression of nephropathy to a greater extent . FUNDING Novartis
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 .