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 .
The Evening versus Morning Polypill Utilization Study: the TEMPUS rationale and design
Background and rationale In clinical practice , blood pressure (BP)-lowering agents are generally prescribed for use in the morning , whereas ( short-acting ) statins are recommended for use in the evening . There is evidence that the reduction in LDL cholesterol ( LDL-c ) achieved with short-acting statins is superior when taken in the evening and reported improvement in BP control when aspirin and BP-lowering agents are taken in the evening . However , it is unclear whether the additional reduction in LDL-c and BP is offset by a reduction in adherence , given that taking medication in the evening may be less typical or convenient . There is therefore uncertainty concerning the best timing of administration of a cardiovascular combination pill such as the polypill . Aim The aim of TEMPUS ( NCT01506505 ) , a prospect i ve r and omized open blinded endpoint ( PROBE ) crossover trial , is to evaluate whether there is a difference in LDL-c levels or 24-hour ambulatory BP in individuals at increased risk of cardiovascular disease when the cardiovascular polypill is taken in the evening compared to the morning . An additional aim is to assess the effect of the polypill on LDL-c and BP compared to the administration of separate pills of identically dosed components of the polypill . Methods In total 75 participants with established cardiovascular disease or an intermediate to high risk for cardiovascular disease are r and omly allocated to the sequence of three different treatments of 6–8 weeks : ( 1 ) the cardiovascular polypill ( aspirin 75 mg , simvastatin 40 mg , lisinopril 10 mg , and hydrochlorothiazide 12.5 mg ) in the evening ; ( 2 ) the polypill in the morning ; and ( 3 ) the use of the identically dosed agents in separate pills taken at different time points during the day . The primary endpoint is the difference in LDL-c and mean 24-hour ambulatory systolic BP . Secondary outcomes are the difference in relative risk reduction , biochemistry , platelet function and pulse wave analysis , participants ’ adherence , and acceptability . Conclusions TEMPUS will evaluate the effect of timing of the administration of a cardiovascular polypill on LDL-c and BP measurements in patients with an intermediate or high risk for cardiovascular disease
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 .