Reductions in blood pressure and lipid parameters are generally lower than those previously projected , though substantial heterogeneity of results exists .
Fixed-dose combination therapy is associated with modest increases in adverse events compared with placebo , single drug active component , or usual care but may be associated with improved adherence to a multidrug regimen .
BACKGROUND Cardiovascular disease ( CVD ) is the leading cause of death and disability worldwide , yet CVD 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 CVD by up to 80 % given its potential for better adherence and lower costs .
OBJECTIVES To determine the effectiveness of fixed-dose combination therapy on reducing fatal and non-fatal CVD events and on improving blood pressure and lipid CVD risk factors for both primary and secondary prevention of CVD .
We also aim ed to determine discontinuation rates , adverse events , health-related quality of life , and costs of fixed-dose combination therapy .
Preservation of Bioavailability of Ingredients and Lack of Drug-Drug Interactions in a Novel Five-Ingredient Polypill (Polycap™)
Background The Polycap ™ ( polypill ; aspirin [ acetylsalicylic acid ] , ramipril , simvastatin , atenolol , and hydrochlorothiazide ) was found to be safe and effective for reducing multiple  cardiovascular risk factors in The Indian Polycap ™ Study ( TIPS ) . Objective We evaluated the bioavailability of each ingredient of the Polycap ™ and determined any drug-drug interactions relative to single component reference preparations . Methods The bioavailability of the ingredients of the Polycap ™ ( T ; test ) when formulated as a single capsule was compared with that of identical capsules with each of its ingredients administered separately ( R ; reference ) in a five-arm , r and omized , single-dose , two-period , two-treatment , two-sequence , crossover trial with at least a 2-week washout period in a total of 195 healthy volunteers . Plasma concentrations of each drug and , where applicable , its active metabolite were measured using vali date d liquid chromatographyt and em mass spectrometry and ultra-performance liquid chromatography . Mean pharmacokinetic parameters and their st and ard deviations were computed for each analyte . Results Comparative bioavailability was computed and no drug-drug interactions and no difference in comparative bioavailability were concluded for each ingredient based on point estimates of the T/R ratio of the geometric means falling within 80–125 % for peak plasma concentration ( Cmax ) , area under the plasma concentration-time curve from time zero to the last measurable concentration ( AUCt ) , and AUC from time zero to infinity ( AUC∞ ) . The T/R ratio for Cmax , AUCt and AUC∞ was within 80–125 % for atenolol , hydrochlorothiazide , ramipril , ramiprilat and dose-normalized salicylic acid . However , for simvastatin , the T/R point estimates for Cmax , AUCt and AUC∞ for Ln-transformed data were significantly lower ( ∼3–4 % ) than the lower bound of 80 % . For its active metabolite , simvastatin acid , these estimates were significantly higher ( ∼25–35 % ) than the higher bound of 125 % . Thus , the increased bioavailability of active simvastatin acid appeared to compensate for the loss of bioavailability of simvastatin . Conclusion The Polycap ™ was found to be effective and safe in the previously published TIPS trial . The present study in healthy volunteers establishes that Polycap ™ is safe ( no serious adverse events ) and well tolerated , and that there is no indication of pharmacokinetic drug-drug interactions for any of the ingredients , with their bioavailabilities being well preserved
Reductions in blood pressure and lipid parameters are generally lower than those previously projected , though substantial heterogeneity of results exists .
Fixed-dose combination therapy is associated with modest increases in adverse events compared with placebo , single drug active component , or usual care but may be associated with improved adherence to a multidrug regimen .
BACKGROUND Cardiovascular disease ( CVD ) is the leading cause of death and disability worldwide , yet CVD 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 CVD by up to 80 % given its potential for better adherence and lower costs .
OBJECTIVES To determine the effectiveness of fixed-dose combination therapy on reducing fatal and non-fatal CVD events and on improving blood pressure and lipid CVD risk factors for both primary and secondary prevention of CVD .
We also aim ed to determine discontinuation rates , adverse events , health-related quality of life , and costs of fixed-dose combination therapy .