human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Patients with grade 2 or 3 hypertension may require high-dose combination therapy to achieve blood pressure ( BP ) targets in a timely manner . OBJECTIVES This study compared the effectiveness and tolerability of a single-pill combination ( SPC ) of telmisartan/hydrochlorothiazide 80/25 mg ( T80/H25 ) with T80 monotherapy . METHODS In a Phase IV , multinational , r and omized , double-blind , double-dummy , active-controlled , parallel-group trial , 894 patients with mean seated trough cuff systolic BP [ SBP ] ≥160 mm Hg and diastolic BP [ DBP ] ≥100 mm Hg were r and omly assigned in a 2:1 ratio to receive T40/H12.5 SPC or telmisartan 40 mg monotherapy for 1 week before the dose was uptitrated to T80/H25 SPC or T80 , respectively , administered for 6 weeks . The primary efficacy measure was the change from baseline in mean seated cuff trough SBP . Adverse events ( AEs ) were recorded . RESULTS A total of 888 patients received treatment ( 294 and 594 patients in the T80/H25 and T80 groups , respectively ) ( mean age , 57.0 years ; age ≥65 years , 25.7 % ; male , 53.8 % ; white , 68.0 % ) ; 61 patients prematurely  discontinued . Mean baseline SBP/DBP values were 172.3/104.3 mm Hg ( T80/H25 ) and 173.3/104.5 mm Hg ( T80 ) . After 7 weeks , SBP was changed by -37.0 and -28.5 mm Hg in the T80/H25 and T80 groups ( P < 0.0001 ) ; DBP was changed by -18.6 and -15.4 mm Hg respectively ( P < 0.0001 ) . These differences were significant after 2 weeks at the higher dosage ( P < 0.0001 ) . BP target ( SBP/DBP < 140/<90 mm Hg ) was achieved in 55.5 % and 34.7 % of patients in the T80/H25 and T80 groups ( P < 0.0001 ) . T80/H25 SPC and T80 had a similar frequency of overall AEs ( 16.0 % vs 17.0 % ) . The prevalences of treatment-related AEs with T80/H25 SPC and T80 were low ( 4.6 % and 2.8 % ) , as were the rates of AEs that led to discontinuation ( 1.0 % and 2.8 % ) . CONCLUSIONS In these patients with grade 2 or 3 hypertension , initial therapy with T80/H25 was associated with a significantly greater reduction in mean seated cuff trough SBP compared with T80 alone , as well as with improved hypertension goal attainment rates . Both treatments appeared to be well tolerated Background The Kanyini Guidelines Adherence with the Polypill ( Kanyini-GAP ) Study aims to examine whether a polypill-based strategy ( using a single capsule containing aspirin , a statin and two blood pressure-lowering agents ) amongst Indigenous and non-Indigenous people at high risk of experiencing a cardiovascular event will improve adherence to guideline -indicated therapies , and lower blood pressure and cholesterol levels . Methods / Design The study is an open , r and omised , controlled , multi-centre trial involving 1000 participants at high risk of cardiovascular events recruited from mainstream general practice s and Aboriginal Medical Services , followed for an average of 18 months . The participants will be r and omised to one of two  versions  of  the polypill  , the version chosen by the treating health professional according to clinical features of the patient , or to usual care . The primary study outcomes will be changes , from baseline measures , in serum cholesterol and systolic blood pressure and self-reported current use of aspirin , a statin and at least two blood pressure lowering agents . Secondary study outcomes include cardiovascular events , renal outcomes , self-reported barriers to indicated therapy , prescription of indicated therapy , occurrence of serious adverse events and changes in quality -of-life . The trial will be supplemented by formal economic and process evaluations . Discussion The Kanyini-GAP trial will provide new evidence as to whether or not a polypill-based strategy improves adherence to effective cardiovascular medications amongst individuals in whom these treatments are indicated . Trial Registration This trial is registered with the Australian New Zeal and Clinical Trial Registry ACTRN126080005833347 Background There has been widespread interest in the potential of combination cardiovascular medications containing aspirin and agents to lower blood pressure and cholesterol ( ‘ polypills ’ ) to reduce cardiovascular disease . However , no reliable placebo-controlled data are available on both efficacy and tolerability . Methods We conducted a r and omised , double-blind placebo-controlled trial of a polypill ( containing aspirin 75 mg , lisinopril 10 mg , hydrochlorothiazide 12.5 mg and simvastatin 20 mg ) in 378 individuals without an indication for any component of the polypill , but who had an estimated 5-year cardiovascular disease risk over 7.5 % . The primary outcomes were systolic blood pressure ( SBP ) , LDL-cholesterol and tolerability ( proportion discontinued r and omised therapy ) at 12 weeks follow-up . Findings At baseline , mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 mmol/L. Over 12 weeks , polypill treatment reduced SBP by 9.9 ( 95 % CI : 7.7 to 12.1 ) mmHg and LDL-cholesterol by 0.8 ( 95 % CI 0.6 to 0.9 ) mmol/L. The discontinuation rates in the polypill group compared to placebo were 23 % vs 18 % ( RR 1.33 , 95 % CI 0.89 to 2.00 , p = 0.2 ) . There was an excess of side effects known to the component medicines ( 58 % vs 42 % , p = 0.001 ) , which was mostly apparent within a few weeks , and usually did not warrant cessation of trial treatment . Conclusions This polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6 people . The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate is moderately higher . Nonetheless , substantial net benefits would be expected among patients at high risk . Trial Registration Australian New Zeal and Clinical Trials Registry Background — A daily single capsule ( polycap ) of 3 blood pressure ( BP ) lowering drugs ( hydrochlorthiazide , 12.5 mg ; atenolol , 50 mg ; ramipril , 5 mg ) at low doses , simvastatin ( 20 mg ) , and aspirin ( 100 mg ) has been demonstrated to be well tolerated and to reduce BP and low-density lipoprotein cholesterol . We examined the incremental effects of 2 ( full dose ) plus K+ supplementation versus single polycap ( low dose ) on risk factors and tolerability . Methods and Results — After a run-in period , 518 individuals with previous vascular disease or diabetes mellitus from 27 centers in India were r and omly assigned to a single-dose polycap or to 2 capsules of the polycap plus K+ supplementation for 8 weeks . The effects on BP , heart rate ( HR ) , serum lipids , serum and urinary K+ , and tolerability were assessed using an intention-to-treat analysis . The full-dose polycap ( plus K+ supplementation )  reduced BP by a further 2.8 mm Hg systolic and 1.7 mm Hg diastolic , compared with that observed with the low-dose polycap ( P=0.003 ; P=0.001 ) , but there were no differences in HR ( 0.1 bpm ) . The differences in total and low-density lipoprotein cholesterol between the full-dose and low-dose polycap was 7.2 mg/dL ( P=0.014 ) and 6.6 mg/dL ( P=0.006 ) , respectively , but there were no differences in high-density lipoprotein cholesterol or triglycerides . The rates of discontinuation of the study drug after r and omization were similar in the 2 groups ( 6.9 % low dose versus 7.8 % full dose ) . Conclusions — The full-dose polycap ( plus K+ supplementation ) reduces BP and low-density lipoprotein cholesterol to a greater extent compared with the low dose , with similar tolerability . Therefore , the full-dose polycap should potentially lead to larger benefits . Clinical Trial Registration — URL : http://www.ctri.nic.in . Unique identifier : CTRI/2010/091/000054 IMPORTANCE Most patients with cardiovascular disease ( CVD ) do not take recommended medications long-term . The use of fixed-dose combinations ( FDCs ) improves adherence in several clinical areas . Previous trials of cardiovascular FDCs have assessed short-term effects compared with placebo or no treatment . OBJECTIVE To assess whether FDC delivery of aspirin , statin , and 2 blood pressure-lowering agents vs usual care improves long-term adherence to indicated therapy and 2 major CVD risk factors , systolic blood pressure ( SBP ) and low-density lipoprotein cholesterol ( LDL-C ) . DESIGN , SETTING , AND PARTICIPANTS The UMPIRE trial , a r and omized , open-label , blinded-end-point trial among 2004 participants with established CVD or at risk of CVD enrolled July 2010-July 2011 in India and Europe . The trial follow-up concluded in July 2012 . INTERVENTIONS Participants were r and omly assigned ( 1:1 ) to an FDC-based strategy  ( n=1002 ) containing either ( 1 ) 75 mg aspirin , 40 mg simvastatin , 10 mg lisinopril , and 50 mg atenolol or ( 2 ) 75 mg aspirin , 40 mg simvastatin , 10 mg lisinopril , and 12.5 mg hydrochlorothiazide or to usual care ( n=1002 ) . MAIN OUTCOMES AND MEASURES Adherence to medication ( defined as self-reported use of antiplatelet , statin , and ≥2 BP-lowering medications ) and changes in SBP and LDL-C from baseline . RESULTS At baseline , mean BP was 137/78 mm Hg , LDL-C was 91.5 mg/dL , and 1233 ( 61.5 % ) of 2004 participants reported use of antiplatelet , statin , and 2 or more BP-lowering medications . Median follow-up was 15 months ( interquartile range , 12 - 18 months ) . The FDC group had improved adherence vs usual care ( 86 % vs 65 % ; relative risk [ RR ] of being adherent , 1.33 ; 95 % CI , 1.26 - 1.41 ; P < .001 ) with concurrent reductions in SBP ( -2.6 mm Hg ; 95 % CI , -4.0 to -1.1 mm Hg ; P < .001 ) and LDL-C ( -4.2 mg/dL ; 95 % CI , -6.6 to -1.9 mg/dL ; P < .001 ) at the end of the study . Although there was consistency of effects across predefined subgroups , evidence existed of larger benefits in patients with lower adherence at baseline . In this subgroup of 727 participants ( 36 % ) , adherence at the end of study was 77 % vs 23 % ( RR , 3.35 ; 95 % CI , 2.74 - 4.09 ; P < .001 for interaction ) , SBP was reduced by 4.9 mm Hg ( 95 % CI 7.3 - 2.6 mm Hg ; P = .01 for interaction ) , and LDL-C was reduced by 6.7 mg/dL ( 95 % CI , 10.5 - 2.8 mg/dL ; P = .11 for interaction ) . There were no significant differences in serious adverse events or cardiovascular events ( 50 [ 5 % ] in the FDC group and 35 [ 3.5 % ] in the usual care group ; RR , 1.45 ; 95 % CI , 0.94 - 2.24 ; P=.09 ) between the groups . CONCLUSIONS AND RELEVANCE Among patients with or at high risk of CVD , use of an FDC strategy for blood pressure , cholesterol , and platelet control vs usual care result ed in significantly improved medication adherence at 15 months and statistically significant but small improvements in SBP and LDL-C. TRIAL REGISTRATION clin 
    Output:
    
agent
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 .
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Patients with grade 2 or 3 hypertension may require high-dose combination therapy to achieve blood pressure ( BP ) targets in a timely manner . OBJECTIVES This study compared the effectiveness and tolerability of a single-pill combination ( SPC ) of telmisartan/hydrochlorothiazide 80/25 mg ( T80/H25 ) with T80 monotherapy . METHODS In a Phase IV , multinational , r and omized , double-blind , double-dummy , active-controlled , parallel-group trial , 894 patients with mean seated trough cuff systolic BP [ SBP ] ≥160 mm Hg and diastolic BP [ DBP ] ≥100 mm Hg were r and omly assigned in a 2:1 ratio to receive T40/H12.5 SPC or telmisartan 40 mg monotherapy for 1 week before the dose was uptitrated to T80/H25 SPC or T80 , respectively , administered for 6 weeks . The primary efficacy measure was the change from baseline in mean seated cuff trough SBP . Adverse events ( AEs ) were recorded . RESULTS A total of 888 patients received treatment ( 294 and 594 patients in the T80/H25 and T80 groups , respectively ) ( mean age , 57.0 years ; age ≥65 years , 25.7 % ; male , 53.8 % ; white , 68.0 % ) ; 61 patients prematurely  discontinued . Mean baseline SBP/DBP values were 172.3/104.3 mm Hg ( T80/H25 ) and 173.3/104.5 mm Hg ( T80 ) . After 7 weeks , SBP was changed by -37.0 and -28.5 mm Hg in the T80/H25 and T80 groups ( P < 0.0001 ) ; DBP was changed by -18.6 and -15.4 mm Hg respectively ( P < 0.0001 ) . These differences were significant after 2 weeks at the higher dosage ( P < 0.0001 ) . BP target ( SBP/DBP < 140/<90 mm Hg ) was achieved in 55.5 % and 34.7 % of patients in the T80/H25 and T80 groups ( P < 0.0001 ) . T80/H25 SPC and T80 had a similar frequency of overall AEs ( 16.0 % vs 17.0 % ) . The prevalences of treatment-related AEs with T80/H25 SPC and T80 were low ( 4.6 % and 2.8 % ) , as were the rates of AEs that led to discontinuation ( 1.0 % and 2.8 % ) . CONCLUSIONS In these patients with grade 2 or 3 hypertension , initial therapy with T80/H25 was associated with a significantly greater reduction in mean seated cuff trough SBP compared with T80 alone , as well as with improved hypertension goal attainment rates . Both treatments appeared to be well tolerated Background The Kanyini Guidelines Adherence with the Polypill ( Kanyini-GAP ) Study aims to examine whether a polypill-based strategy ( using a single capsule containing aspirin , a statin and two blood pressure-lowering agents ) amongst Indigenous and non-Indigenous people at high risk of experiencing a cardiovascular event will improve adherence to guideline -indicated therapies , and lower blood pressure and cholesterol levels . Methods / Design The study is an open , r and omised , controlled , multi-centre trial involving 1000 participants at high risk of cardiovascular events recruited from mainstream general practice s and Aboriginal Medical Services , followed for an average of 18 months . The participants will be r and omised to one of two  versions  of  the polypill  , the version chosen by the treating health professional according to clinical features of the patient , or to usual care . The primary study outcomes will be changes , from baseline measures , in serum cholesterol and systolic blood pressure and self-reported current use of aspirin , a statin and at least two blood pressure lowering agents . Secondary study outcomes include cardiovascular events , renal outcomes , self-reported barriers to indicated therapy , prescription of indicated therapy , occurrence of serious adverse events and changes in quality -of-life . The trial will be supplemented by formal economic and process evaluations . Discussion The Kanyini-GAP trial will provide new evidence as to whether or not a polypill-based strategy improves adherence to effective cardiovascular medications amongst individuals in whom these treatments are indicated . Trial Registration This trial is registered with the Australian New Zeal and Clinical Trial Registry ACTRN126080005833347 Background There has been widespread interest in the potential of combination cardiovascular medications containing aspirin and agents to lower blood pressure and cholesterol ( ‘ polypills ’ ) to reduce cardiovascular disease . However , no reliable placebo-controlled data are available on both efficacy and tolerability . Methods We conducted a r and omised , double-blind placebo-controlled trial of a polypill ( containing aspirin 75 mg , lisinopril 10 mg , hydrochlorothiazide 12.5 mg and simvastatin 20 mg ) in 378 individuals without an indication for any component of the polypill , but who had an estimated 5-year cardiovascular disease risk over 7.5 % . The primary outcomes were systolic blood pressure ( SBP ) , LDL-cholesterol and tolerability ( proportion discontinued r and omised therapy ) at 12 weeks follow-up . Findings At baseline , mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 mmol/L. Over 12 weeks , polypill treatment reduced SBP by 9.9 ( 95 % CI : 7.7 to 12.1 ) mmHg and LDL-cholesterol by 0.8 ( 95 % CI 0.6 to 0.9 ) mmol/L. The discontinuation rates in the polypill group compared to placebo were 23 % vs 18 % ( RR 1.33 , 95 % CI 0.89 to 2.00 , p = 0.2 ) . There was an excess of side effects known to the component medicines ( 58 % vs 42 % , p = 0.001 ) , which was mostly apparent within a few weeks , and usually did not warrant cessation of trial treatment . Conclusions This polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6 people . The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate is moderately higher . Nonetheless , substantial net benefits would be expected among patients at high risk . Trial Registration Australian New Zeal and Clinical Trials Registry Background — A daily single capsule ( polycap ) of 3 blood pressure ( BP ) lowering drugs ( hydrochlorthiazide , 12.5 mg ; atenolol , 50 mg ; ramipril , 5 mg ) at low doses , simvastatin ( 20 mg ) , and aspirin ( 100 mg ) has been demonstrated to be well tolerated and to reduce BP and low-density lipoprotein cholesterol . We examined the incremental effects of 2 ( full dose ) plus K+ supplementation versus single polycap ( low dose ) on risk factors and tolerability . Methods and Results — After a run-in period , 518 individuals with previous vascular disease or diabetes mellitus from 27 centers in India were r and omly assigned to a single-dose polycap or to 2 capsules of the polycap plus K+ supplementation for 8 weeks . The effects on BP , heart rate ( HR ) , serum lipids , serum and urinary K+ , and tolerability were assessed using an intention-to-treat analysis . The full-dose polycap ( plus K+ supplementation )  reduced BP by a further 2.8 mm Hg systolic and 1.7 mm Hg diastolic , compared with that observed with the low-dose polycap ( P=0.003 ; P=0.001 ) , but there were no differences in HR ( 0.1 bpm ) . The differences in total and low-density lipoprotein cholesterol between the full-dose and low-dose polycap was 7.2 mg/dL ( P=0.014 ) and 6.6 mg/dL ( P=0.006 ) , respectively , but there were no differences in high-density lipoprotein cholesterol or triglycerides . The rates of discontinuation of the study drug after r and omization were similar in the 2 groups ( 6.9 % low dose versus 7.8 % full dose ) . Conclusions — The full-dose polycap ( plus K+ supplementation ) reduces BP and low-density lipoprotein cholesterol to a greater extent compared with the low dose , with similar tolerability . Therefore , the full-dose polycap should potentially lead to larger benefits . Clinical Trial Registration — URL : http://www.ctri.nic.in . Unique identifier : CTRI/2010/091/000054 IMPORTANCE Most patients with cardiovascular disease ( CVD ) do not take recommended medications long-term . The use of fixed-dose combinations ( FDCs ) improves adherence in several clinical areas . Previous trials of cardiovascular FDCs have assessed short-term effects compared with placebo or no treatment . OBJECTIVE To assess whether FDC delivery of aspirin , statin , and 2 blood pressure-lowering agents vs usual care improves long-term adherence to indicated therapy and 2 major CVD risk factors , systolic blood pressure ( SBP ) and low-density lipoprotein cholesterol ( LDL-C ) . DESIGN , SETTING , AND PARTICIPANTS The UMPIRE trial , a r and omized , open-label , blinded-end-point trial among 2004 participants with established CVD or at risk of CVD enrolled July 2010-July 2011 in India and Europe . The trial follow-up concluded in July 2012 . INTERVENTIONS Participants were r and omly assigned ( 1:1 ) to an FDC-based strategy  ( n=1002 ) containing either ( 1 ) 75 mg aspirin , 40 mg simvastatin , 10 mg lisinopril , and 50 mg atenolol or ( 2 ) 75 mg aspirin , 40 mg simvastatin , 10 mg lisinopril , and 12.5 mg hydrochlorothiazide or to usual care ( n=1002 ) . MAIN OUTCOMES AND MEASURES Adherence to medication ( defined as self-reported use of antiplatelet , statin , and ≥2 BP-lowering medications ) and changes in SBP and LDL-C from baseline . RESULTS At baseline , mean BP was 137/78 mm Hg , LDL-C was 91.5 mg/dL , and 1233 ( 61.5 % ) of 2004 participants reported use of antiplatelet , statin , and 2 or more BP-lowering medications . Median follow-up was 15 months ( interquartile range , 12 - 18 months ) . The FDC group had improved adherence vs usual care ( 86 % vs 65 % ; relative risk [ RR ] of being adherent , 1.33 ; 95 % CI , 1.26 - 1.41 ; P < .001 ) with concurrent reductions in SBP ( -2.6 mm Hg ; 95 % CI , -4.0 to -1.1 mm Hg ; P < .001 ) and LDL-C ( -4.2 mg/dL ; 95 % CI , -6.6 to -1.9 mg/dL ; P < .001 ) at the end of the study . Although there was consistency of effects across predefined subgroups , evidence existed of larger benefits in patients with lower adherence at baseline . In this subgroup of 727 participants ( 36 % ) , adherence at the end of study was 77 % vs 23 % ( RR , 3.35 ; 95 % CI , 2.74 - 4.09 ; P < .001 for interaction ) , SBP was reduced by 4.9 mm Hg ( 95 % CI 7.3 - 2.6 mm Hg ; P = .01 for interaction ) , and LDL-C was reduced by 6.7 mg/dL ( 95 % CI , 10.5 - 2.8 mg/dL ; P = .11 for interaction ) . There were no significant differences in serious adverse events or cardiovascular events ( 50 [ 5 % ] in the FDC group and 35 [ 3.5 % ] in the usual care group ; RR , 1.45 ; 95 % CI , 0.94 - 2.24 ; P=.09 ) between the groups . CONCLUSIONS AND RELEVANCE Among patients with or at high risk of CVD , use of an FDC strategy for blood pressure , cholesterol , and platelet control vs usual care result ed in significantly improved medication adherence at 15 months and statistically significant but small improvements in SBP and LDL-C. TRIAL REGISTRATION clin 
    Output:
    