The effects of fixed-dose combination therapy on all-cause mortality or ASCVD events are uncertain .
A limited number of trials reported these outcomes , and the included trials were primarily design ed to observe changes in ASCVD risk factor levels rather than clinical events , which may partially explain the observed differences in risk factors that were not translated into differences in clinical outcomes among the included trials .
Fixed-dose combination therapy is associated with modest increases in adverse events compared with placebo , active comparator , or usual care but may be associated with improved adherence to a multidrug regimen .
Ongoing , longer-term trials of fixed-dose combination therapy will help demonstrate whether short-term changes in risk factors might be maintained and lead to expected differences in clinical events based on these changes
BACKGROUND Atherosclerotic cardiovascular disease ( ASCVD ) is the leading cause of death and disability worldwide , yet ASCVD risk factor control and secondary prevention rates remain low .
A fixed-dose combination of blood pressure- and cholesterol-lowering and antiplatelet treatments into a single pill , or polypill , has been proposed as one strategy to reduce the global burden of ASCVD .
OBJECTIVES To determine the effect of fixed-dose combination therapy on all-cause mortality , fatal and non-fatal ASCVD events , and adverse events .
We also sought to determine the effect of fixed-dose combination therapy on blood pressure , lipids , adherence , discontinuation rates , health-related quality of life , and costs .
Olmesartan/amlodipine/hydrochlorothiazide in participants with hypertension and diabetes, chronic kidney disease, or chronic cardiovascular disease: a subanalysis of the multicenter, randomized, double-blind, parallel-group TRINITY study
Background Patients with hypertension and cardiovascular disease ( CVD ) , diabetes , or chronic kidney disease ( CKD ) usually require two or more antihypertensive agents to achieve blood pressure ( BP ) goals . Methods The efficacy/safety of olmesartan ( OM ) 40 mg , amlodipine besylate ( AML ) 10 mg , and hydrochlorothiazide ( HCTZ ) 25 mg versus the component dual-combinations ( OM 40/AML 10 mg , OM 40/HCTZ 25 mg , and AML 10/HCTZ 25 mg ) was evaluated in participants with diabetes , CKD , or chronic CVD in the Triple Therapy with Olmesartan Medoxomil , Amlodipine , and Hydrochlorothiazide in Hypertensive Patients Study ( TRINITY ) . The primary efficacy end point was least squares ( LS ) mean reduction from baseline in seated diastolic BP ( SeDBP ) at week 12 . Secondary end points included LS mean reduction in SeSBP and proportion of participants achieving BP goal ( < 130/80 mm Hg ) at week 12 ( double-blind r and omized period ) , and LS mean reduction in SeBP and BP goal achievement at week 52/early termination ( open-label period ) . Results At week 12 , OM 40/AML 10/HCTZ 25 mg result ed in significantly greater SeBP reductions in participants with diabetes ( −37.9/22.0 mm Hg vs −28.0/17.6 mm Hg for OM 40/AML 10 mg , −26.4/14.7 mm Hg for OM 40/HCTZ 25 mg , and −27.6/14.8 mm Hg for AML 10/HCTZ 25 mg ) , CKD ( −44.3/25.5 mm Hg vs −39.5/23.8 mm Hg for OM 40/AML 10 mg , −25.3/17.0 mm Hg for OM 40/HCTZ 25 mg , and −33.4/20.6 mm Hg for AML 10/HCTZ 25 mg ) , and chronic CVD ( −37.8/20.6 mm Hg vs −31.7/18.2 mm Hg for OM 40/AML 10 mg , −30.9/17.1 mm Hg for OM 40/HCTZ 25 mg , and −27.5/16.1 mm Hg for AML 10/HCTZ 25 mg ) ( P<0.05 for all subgroups vs dual-component treatments ) . BP goal achievement was greater for participants receiving triple-combination treatment compared with the dual-combination treatments , and was achieved in 41.1 % , 55.0 % , and 38.9 % of participants with diabetes , CKD , and chronic CVD on OM 40/AML 10/HCTZ 25 mg , respectively . At week 52 , there was sustained BP lowering with the OM/AML/HCTZ regimen . Overall , the triple combination was well tolerated . Conclusions In patients with diabetes , CKD , or chronic CVD , short-term ( 12 weeks ) and long-term treatment with OM 40/AML 10/HCTZ 25 mg was well tolerated , lowered BP more effectively , and enabled more participants to reach BP goal than the corresponding 2-component regimens . Trial Identification
The effects of fixed-dose combination therapy on all-cause mortality or ASCVD events are uncertain .
A limited number of trials reported these outcomes , and the included trials were primarily design ed to observe changes in ASCVD risk factor levels rather than clinical events , which may partially explain the observed differences in risk factors that were not translated into differences in clinical outcomes among the included trials .
Fixed-dose combination therapy is associated with modest increases in adverse events compared with placebo , active comparator , or usual care but may be associated with improved adherence to a multidrug regimen .
Ongoing , longer-term trials of fixed-dose combination therapy will help demonstrate whether short-term changes in risk factors might be maintained and lead to expected differences in clinical events based on these changes
BACKGROUND Atherosclerotic cardiovascular disease ( ASCVD ) is the leading cause of death and disability worldwide , yet ASCVD risk factor control and secondary prevention rates remain low .
A fixed-dose combination of blood pressure- and cholesterol-lowering and antiplatelet treatments into a single pill , or polypill , has been proposed as one strategy to reduce the global burden of ASCVD .
OBJECTIVES To determine the effect of fixed-dose combination therapy on all-cause mortality , fatal and non-fatal ASCVD events , and adverse events .
We also sought to determine the effect of fixed-dose combination therapy on blood pressure , lipids , adherence , discontinuation rates , health-related quality of life , and costs .