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 .
Zofenopril Plus Hydrochlorothiazide and Irbesartan Plus Hydrochlorothiazide in Previously Treated and Uncontrolled Diabetic and Non-diabetic Essential Hypertensive Patients
Introduction In most treated patients with hypertension , a two or more drug combination is required to achieve adequate blood pressure ( BP ) control . In our study we assessed whether the combination of zofenopril + hydrochlorothiazide ( HCTZ ) was at least as effective as irbesartan + HCTZ in essential hypertensives with at least one additional cardiovascular risk factor , uncontrolled by a previous monotherapy . Methods After a 2-week placebo washout , 361 treated hypertensive patients [ office sitting diastolic BP ( DBP ) , ≥90 mmHg ] , aged 18–75 years , were r and omized double blind to 18-week treatment with zofenopril 30 mg plus HCTZ 12.5 mg or irbesartan 150 mg plus HCTZ 12.5 mg once daily , in an international , multicenter study . After the first 6 and 12 weeks , zofenopril and irbesartan doses could be doubled in non-normalized subjects . The primary study end point was the office sitting DBP reduction after 18 weeks of treatment . Secondary end points included office systolic BP ( SBP ) , ambulatory BP and high sensitivity C-reactive protein ( hs-CRP ) . Results The between-treatment difference for office DBP averaged to + 1.0 ( 95 % CI −0.4 , + 0.8 ) mmHg ( P = 0.150 ) , the upper limit of the 95 % confidence interval being inferior to the protocol -defined non-inferiority limit ( 3 mmHg ) . In the subset of patients with valid ambulatory BP , no difference in 24-h average DBP [ n = 181 ; 6.7 ( 8.7 , 4.6 ) zofenopril + HCTZ vs. 6.3 ( 8.8 , 3.7 ) mmHg irbesartan + HCTZ , P = 0.810 ] and SBP reductions [ 11.7 ( 15.4 , 8.0 ) vs. 12.6 ( 17.2 , 8.0 ) mmHg , P = 0.758 ] were observed between the two treatment groups . hs-CRP was reduced by zofenopril + HCTZ [ −0.52 ( −1.05 , 0.01 ) mg/L ] , while it was increased by irbesartan plus HCTZ [ 0.97 ( 0.29 , 1.65 ) mg/L , P = 0.001 between treatments ] . Conclusion In previously monotherapy-treated , uncontrolled patients with hypertension , zofenopril 30–60 mg + HCTZ 12.5 mg is as effective as irbesartan 150–300 mg plus HCTZ 12.5 mg , with the added value of a potential protective effect against vascular inflammation
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 .