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 .
Pharmacokinetics of rosuvastatin/olmesartan fixed-dose combination: a single-dose, randomized, open-label, 2-period crossover study in healthy Korean subjects.
BACKGROUND Rosuvastatin , a lipid-lowering agent , has been widely used with olmesartan , a long-acting angiotensin II receptor blocker , indicated for the treatment of dyslipidemia accompanied by hypertension . A fixed-dose combination ( FDC ) tablet of these 2 drugs was recently developed to enhance the dosing convenience and to increase patient compliance while yielding pharmacokinetic profiles comparable to coadministration of each drug as individual tablets . OBJECTIVE The goal of present study was to compare the pharmacokinetic profiles of single-dose administration of an FDC tablet containing rosuvastatin/olmesartan 20/40 mg ( test formulation ) with coadministration of a rosuvastatin 20-mg tablet and a olmesartan 40-mg tablet ( reference formulation ) in healthy Korean male volunteers , for the purpose of determining bioequivalence . METHODS This single-dose , r and omized , open-label , 2-period crossover study enrolled subjects aged 20 to 50 years and within 20 % of ideal body weight . Each subject received a single dose of the test and reference formulations orally in a fasted state , with a 7-day washout period between the administrations . Blood sample s were collected up to 72 hours after dosing , and pharmacokinetic parameters were determined for rosuvastatin , its active metabolite ( N-desmethyl rosuvastatin ) , and olmesartan . Bioequivalence was concluded if the 90 % CIs of the geometric mean ratios for the primary pharmacokinetic parameters were within the predetermined range of 80 % to 125 % . Adverse events ( AEs ) were evaluated based on subject interviews and physical examinations . RESULTS Among the 58 enrolled subjects , 54 completed the study . The 90 % CIs of the geometric mean ratios of the primary pharmacokinetic parameters were as follows : rosuvastatin : AUC(last ) , 85.60 % to 97.40 % and C(max ) , 83.16 % to 98.21 % ; N-desmethyl rosuvastatin : AUC(last ) , 82.08 % to 93.45 % and C(max ) , 79.23 % to 93.41 % ; and olmesartan : AUC(last ) , 97.69 % to 105.69 % and C(max ) , 100.35 % to 109.42 % . The most frequently noted AE was headache , occurring in 3 and 6 patients with the test and reference formulations , respectively . All of the AEs were expected , and there was no significant difference in the prevalences of AEs between the 2 formulations . CONCLUSIONS The pharmacokinetic properties of the newly developed FDC tablet of rosuvastatin/olmesartan 20/40 mg suggest that it is bioequivalent to co-administration of each drug as individual tablets in these healthy Korean male subjects . The two formulations were well tolerated , with no serious AEs observed . Clinical Trials.gov identifier : NCT01823900
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 .