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 and Objectives We compared the efficacy and safety of valsartan and rosuvastatin combination therapy with each treatment alone in hypercholesterolemic hypertensive patients . Subjects and Methods Patients who met inclusion criteria were r and omized to receive 1 of the following 2-month drug regimens :  valsartan 160 mg plus rosuvastatin 20 mg , valsartan 160 mg plus placebo , or rosuvastatin 20 mg plus placebo . The primary efficacy variables were change in sitting diastolic blood pressure ( sitDBP ) and sitting systolic blood pressure ( sitSBP ) , and percentage change in low-density lipoprotein-cholesterol ( LDL-C ) in the combination , valsartan , and rosuvastatin groups . Adverse events ( AEs ) during the study were analyzed . Results A total of 354 patients were screened and 123 of them were finally r and omized .  Changes of sitDBP by least squares mean ( LSM ) were -11.1 , -7.2 , and -3.6 mm Hg , respectively , and was greater in the combination , as compared to both valsartan ( p=0.02 ) and rosuvastatin ( p<0.001 ) . Changes of sitSBP by LSM were -13.2 , -10.8 , and -4.9 mm Hg , and was greater in the combination , as compared to rosuvastatin ( p=0.006 ) and not valsartan ( p=0.42 ) . Percentage changes of LDL-C by LSM were -52 , -4 , and -47 % in each group , and was greater in the combination , as compared to valsartan ( p<0.001 ) , similar to rosuvastatin ( p=0.16 ) . Most AEs were mild and resolved by the end of the study . Conclusion Combination treatment with valsartan and rosuvastatin exhibited an additive blood pressure-lowering effect with acceptable tolerability , as compared to valsartan monotherapy . Its lipid lowering effect was similar to rosuvatatin monotherapy Despite race , ethnic , and regional differences in cardiovascular disease risk , many worldwide hypertension management guidelines recommend the use of the Framingham coronary heart disease ( CHD ) risk equation to guide treatment decisions . This sub analysis of the recently published CRUCIAL trial compared the treatment-related reductions in calculated CHD and stroke risk among Pacific Asian ( PA ) patients using a variety of region-specific risk assessment models . As a result , greater reductions in systolic and diastolic blood pressure , low-density lipoprotein cholesterol , and triglycerides were observed in the proactive multifactorial intervention ( PMI ) arm compared with the usual care arm at Week 52 for PA patients . The relative percentage change in 10-yr CHD risk between baseline and Week 52 in the PMI versus usual care arms was greatest using the NIPPON DATA 80 fatal CHD model ( LS [ least square ] mean difference -42.6 % ) , and similar in the SCORE fatal CHD and Framingham total CHD models ( LS mean difference -29.4 % and -30.8 % , respectively ) . The single-pill based PMI approach is consistently effective in reducing cardiovascular disease risk , evaluated using a variety of risk assessment models . ( Clinical Trials.gov registration number : NCT00407537 BACKGROUND Adherence to evidence -based cardiovascular ( CV ) medications after an acute myocardial infa rct ion ( MI ) is low after the first 6 months . The use of fixed-dose combinations ( FDC ) has been shown to improve treatment adherence and risk factor control . However , no previous r and omized trial has analyzed the impact of a polypill strategy on adherence in post-MI patients . OBJECTIVES The cross-sectional FOCUS ( Fixed-Dose Combination Drug for Secondary Cardiovascular Prevention ) study ( Phase 1 ) aim ed to eluci date factors that interfere with appropriate adherence to CV medications for secondary prevention after an acute MI . Additionally , 695 patients from Phase 1 were r and omized into a controlled trial ( Phase 2 ) to test the effect of a polypill ( containing aspirin 100 mg , simvastatin 40 mg , and ramipril 2.5 , 5 , or 10 mg ) compared with the 3 drugs given separately on adherence , blood pressure , and low-density lipoprotein cholesterol , as well as safety and tolerability over a period of 9 months of follow-up . METHODS In Phase 1 , a 5-country cohort of 2,118 patients was analyzed . Patients were r and omized to either the polypill or 3 drugs separately for Phase 2 . Primary endpoint was adherence to the treatment measured at the final visit by the self-reported Morisky-Green question naire ( MAQ ) and pill count ( patients had to meet both criteria for adherence at the in-person visit to be considered adherent ) . RESULTS In Phase 1 , overall CV medication adherence , defined as an MAQ score of 20 , was 45.5 % . In a multivariable regression model , the risk of being nonadherent ( MAQ < 20 ) was associated with younger age , depression , being on a complex medication regimen , poorer health insurance coverage , and a lower level of social support , with consistent findings across countries . In Phase 2 , the polypill group showed improved adherence compared with the group receiving separate medications after 9 months of follow-up : 50.8 % versus 41 % ( p = 0.019 ; intention-to-treat population ) and 65.7 % versus 55.7 % ( p = 0.012 ; per protocol population ) when using the primary endpoint , attending the final visit with MAQ = 20 and high pill count ( 80 % to 110 % ) combined , to assess adherence . Adherence also was higher in the FDC group when measured by MAQ alone ( 68 % vs. 59 % , p = 0.049 ) . No treatment difference was found at follow-up in mean systolic blood pressure ( 129.6 mm Hg vs. 128.6 mm Hg ) , mean low-density lipoprotein cholesterol levels ( 89.9 mg/dl vs. 91.7 mg/dl ) , serious adverse events ( 23 vs. 21 ) , or death ( 1 , 0.3 % in each group ) . CONCLUSIONS For secondary prevention following acute MI , younger age , depression , and a complex drug treatment plan are associated with lower medication adherence . Meanwhile , adherence is increased in patients with higher insurance coverage levels and social support . Compared with the 3 drugs given separately , the use of a polypill strategy met the primary endpoint for adherence for secondary prevention following an acute MI . ( Fixed Dose Combination Drug [ Polypill ] for Secondary Cardiovascular Prevention [ FOCUS ] ; NCT01321255 ) BACKGROUND AND AIMS Patients with established coronary artery disease ( CAD ) are likely to receive a combination of aspirin , a statin , and blood pressure (BP)-lowering agents . Combining these pharmacologic agents into a cardiovascular combination pill , such as a polypill , could be considered to reduce prescription gaps and nonadherence in high-risk patients . We aim ed to evaluate the effect of the concomitant use of aspirin , a statin , and BP-lowering agent(s ) in patients with CAD on vascular morbidity and mortality  in current clinical practice in an observational study to provide insights in the combination pill concept related to feasibility and applicability . METHODS In total , 2,706 patients with CAD enrolled in the Second Manifestations of ARTerial disease study were followed for the occurrence of a subsequent vascular event ( ie , myocardial infa rct ion , ischemic cerebrovascular accident , vascular death ) and all-cause mortality . The relationship between combination therapy and cardiovascular events and all-cause mortality was assessed using Cox proportional hazards regression models to calculate hazards ratios ( HRs ) with a 95 % CI . Both covariate and propensity score adjusting methods were used to reduce confounding by indication . RESULTS A combination of aspirin , a statin , and ≥1 BP-lowering agent(s ) was used by 67 % of the patients . During a median of 5.0 years ( interquartile range 2.4 - 10.2 years ) , 347 vascular events occurred and 162 patients died . Combination therapy with aspirin , statin , and ≥1 BP-lowering agent was associated with a lower risk of myocardial infa rct ion ( HR 0.68 , 95 % CI 0.49 - 0.96 ) , ischemic cerebrovascular accident ( HR 0.37 , 95 % CI 0.16 - 0.84 ) , composite vascular end point ( HR 0.66 , 95 % CI 0.49 - 0.88 ) , vascular mortality ( HR 0.53 , 95 % CI 0.33 - 0.85 ) , and all-cause mortality ( HR 0.69 , 95 % CI 0.49 - 0.96 ) compared with the absence of combination therapy , after adjusting for confounding covariates in a propensity score . The use of 1 or only 2 components of combination therapy was associated with a higher risk for cardiovascular events compared with the combined use of aspirin , a statin , and ≥1 BP-lowering agent(s ) . CONCLUSION Two-thirds of the patients with CAD use a combination of aspirin , a statin , and ≥1 BP-lowering agent(s ) , components of a cardiovascular fixed-dose combination pill . Combination therapy with these agents is associated with a lower risk of vascular events and total mortality . Although treatment effect in observational studies should be interpreted with caution , the results of this study support supposed benefits from combination therapy . However , the effect of fixed-dose combination pill on clinical outcome needs to be demonstrated in r and omized clinical trials The pill burden of patients with hypertension and dyslipidemia can result in poor medication compliance . This study aim ed to evaluate the efficacy and safety of fixed-dose combination ( FDC ) therapy with olmesartan medoxomil ( 40 mg ) and rosuvastatin ( 20 mg ) in Korean patients with mild to moderate hypertension and dyslipidemia . This multicenter , r and omized , double-blind , factorial- design study included patients aged ≥20 years with mild to moderate essential hypertension and dyslipidemia . Patients were r and omly assigned to receive FDC therapy ( 40 mg olmesartan medoxomil , 20 mg rosuvastatin ) , 40 mg olmesartan medoxomil , 20 mg rosuvastatin , or a placebo . The percentage change from baseline in low-density lipoprotein cholesterol levels was compared between FDC therapy and olmesartan medoxomil , and the change from baseline in diastolic blood pressure was compared between FDC therapy and rosuvastatin 8 weeks after treatment . A total of 162 patients were included . The least square mean percentage change ( st and ard error ) from baseline in low-density lipoprotein cholesterol levels 8 weeks after treatment was significantly greater in the FDC than in the olmesartan medoxomil group ( −52.3 % [ 2.8 % ] vs −0.6 % [ 3.5 % ] , P<0.0001 ) , and the difference was −51.7 % ( 4.1 % ) ( 95 % confidence interval : −59.8 % to −43.6 % ) . The least square mean change ( st and ard error ) from baseline in diastolic blood pressure 8 weeks after treatment was significantly greater in the FDC group than in the rosuvastatin group ( −10.4 [ 1.2 ] mmHg vs 0.1 [ 1.6 ] mmHg , P<0.0001 ) , and the difference was −10.5 ( 1.8 ) mmHg ( 95 % confidence interval : −14.1 to −6.9 mmHg ) . There were 50 adverse events in 41 patients ( 22.7 % ) and eight adverse drug reactions in five patients ( 2.8 % ) . The study found that FDC therapy with olmesartan medoxomil and rosuvastatin is an effective , safe treatment for patients with hypertension and dyslipidemia . This combination may improve medication compliance in patients with a large pill burden Background : Notwithst and ing improving rates of hypertension control in North America , management of patients with both hypertension and dyslipidemia remains problematic . Based on evidence of improved control utilizing a simplified algorithm for management of hypertension ( STITCH ) , we question ed whether a simplified comprehensive treatment algorithm featuring initial use of single-pill combinations ( SPCs ) would improve management of participants with both hypertension and dyslipidemia . Method : We r and omized 35 primary care practice s in Ontario to either Guidelines -care (  following current Canadian guidelines ) or STITCH2-care ( following a treatment algorithm featuring SPCs ) . Practice s each enrolled up to 50 participants with at least one risk factor above target at entry based on Canadian guidelines for BP and LDL-cholesterol control . The primary endpoint was achieving targets for both hypertension and dyslipidemia control after 6 months , assessed at the practice level . Results : The primary endpoint was achieved in 31. 
    Output:
    
agent
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
***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 and Objectives We compared the efficacy and safety of valsartan and rosuvastatin combination therapy with each treatment alone in hypercholesterolemic hypertensive patients . Subjects and Methods Patients who met inclusion criteria were r and omized to receive 1 of the following 2-month drug regimens :  valsartan 160 mg plus rosuvastatin 20 mg , valsartan 160 mg plus placebo , or rosuvastatin 20 mg plus placebo . The primary efficacy variables were change in sitting diastolic blood pressure ( sitDBP ) and sitting systolic blood pressure ( sitSBP ) , and percentage change in low-density lipoprotein-cholesterol ( LDL-C ) in the combination , valsartan , and rosuvastatin groups . Adverse events ( AEs ) during the study were analyzed . Results A total of 354 patients were screened and 123 of them were finally r and omized .  Changes of sitDBP by least squares mean ( LSM ) were -11.1 , -7.2 , and -3.6 mm Hg , respectively , and was greater in the combination , as compared to both valsartan ( p=0.02 ) and rosuvastatin ( p<0.001 ) . Changes of sitSBP by LSM were -13.2 , -10.8 , and -4.9 mm Hg , and was greater in the combination , as compared to rosuvastatin ( p=0.006 ) and not valsartan ( p=0.42 ) . Percentage changes of LDL-C by LSM were -52 , -4 , and -47 % in each group , and was greater in the combination , as compared to valsartan ( p<0.001 ) , similar to rosuvastatin ( p=0.16 ) . Most AEs were mild and resolved by the end of the study . Conclusion Combination treatment with valsartan and rosuvastatin exhibited an additive blood pressure-lowering effect with acceptable tolerability , as compared to valsartan monotherapy . Its lipid lowering effect was similar to rosuvatatin monotherapy Despite race , ethnic , and regional differences in cardiovascular disease risk , many worldwide hypertension management guidelines recommend the use of the Framingham coronary heart disease ( CHD ) risk equation to guide treatment decisions . This sub analysis of the recently published CRUCIAL trial compared the treatment-related reductions in calculated CHD and stroke risk among Pacific Asian ( PA ) patients using a variety of region-specific risk assessment models . As a result , greater reductions in systolic and diastolic blood pressure , low-density lipoprotein cholesterol , and triglycerides were observed in the proactive multifactorial intervention ( PMI ) arm compared with the usual care arm at Week 52 for PA patients . The relative percentage change in 10-yr CHD risk between baseline and Week 52 in the PMI versus usual care arms was greatest using the NIPPON DATA 80 fatal CHD model ( LS [ least square ] mean difference -42.6 % ) , and similar in the SCORE fatal CHD and Framingham total CHD models ( LS mean difference -29.4 % and -30.8 % , respectively ) . The single-pill based PMI approach is consistently effective in reducing cardiovascular disease risk , evaluated using a variety of risk assessment models . ( Clinical Trials.gov registration number : NCT00407537 BACKGROUND Adherence to evidence -based cardiovascular ( CV ) medications after an acute myocardial infa rct ion ( MI ) is low after the first 6 months . The use of fixed-dose combinations ( FDC ) has been shown to improve treatment adherence and risk factor control . However , no previous r and omized trial has analyzed the impact of a polypill strategy on adherence in post-MI patients . OBJECTIVES The cross-sectional FOCUS ( Fixed-Dose Combination Drug for Secondary Cardiovascular Prevention ) study ( Phase 1 ) aim ed to eluci date factors that interfere with appropriate adherence to CV medications for secondary prevention after an acute MI . Additionally , 695 patients from Phase 1 were r and omized into a controlled trial ( Phase 2 ) to test the effect of a polypill ( containing aspirin 100 mg , simvastatin 40 mg , and ramipril 2.5 , 5 , or 10 mg ) compared with the 3 drugs given separately on adherence , blood pressure , and low-density lipoprotein cholesterol , as well as safety and tolerability over a period of 9 months of follow-up . METHODS In Phase 1 , a 5-country cohort of 2,118 patients was analyzed . Patients were r and omized to either the polypill or 3 drugs separately for Phase 2 . Primary endpoint was adherence to the treatment measured at the final visit by the self-reported Morisky-Green question naire ( MAQ ) and pill count ( patients had to meet both criteria for adherence at the in-person visit to be considered adherent ) . RESULTS In Phase 1 , overall CV medication adherence , defined as an MAQ score of 20 , was 45.5 % . In a multivariable regression model , the risk of being nonadherent ( MAQ < 20 ) was associated with younger age , depression , being on a complex medication regimen , poorer health insurance coverage , and a lower level of social support , with consistent findings across countries . In Phase 2 , the polypill group showed improved adherence compared with the group receiving separate medications after 9 months of follow-up : 50.8 % versus 41 % ( p = 0.019 ; intention-to-treat population ) and 65.7 % versus 55.7 % ( p = 0.012 ; per protocol population ) when using the primary endpoint , attending the final visit with MAQ = 20 and high pill count ( 80 % to 110 % ) combined , to assess adherence . Adherence also was higher in the FDC group when measured by MAQ alone ( 68 % vs. 59 % , p = 0.049 ) . No treatment difference was found at follow-up in mean systolic blood pressure ( 129.6 mm Hg vs. 128.6 mm Hg ) , mean low-density lipoprotein cholesterol levels ( 89.9 mg/dl vs. 91.7 mg/dl ) , serious adverse events ( 23 vs. 21 ) , or death ( 1 , 0.3 % in each group ) . CONCLUSIONS For secondary prevention following acute MI , younger age , depression , and a complex drug treatment plan are associated with lower medication adherence . Meanwhile , adherence is increased in patients with higher insurance coverage levels and social support . Compared with the 3 drugs given separately , the use of a polypill strategy met the primary endpoint for adherence for secondary prevention following an acute MI . ( Fixed Dose Combination Drug [ Polypill ] for Secondary Cardiovascular Prevention [ FOCUS ] ; NCT01321255 ) BACKGROUND AND AIMS Patients with established coronary artery disease ( CAD ) are likely to receive a combination of aspirin , a statin , and blood pressure (BP)-lowering agents . Combining these pharmacologic agents into a cardiovascular combination pill , such as a polypill , could be considered to reduce prescription gaps and nonadherence in high-risk patients . We aim ed to evaluate the effect of the concomitant use of aspirin , a statin , and BP-lowering agent(s ) in patients with CAD on vascular morbidity and mortality  in current clinical practice in an observational study to provide insights in the combination pill concept related to feasibility and applicability . METHODS In total , 2,706 patients with CAD enrolled in the Second Manifestations of ARTerial disease study were followed for the occurrence of a subsequent vascular event ( ie , myocardial infa rct ion , ischemic cerebrovascular accident , vascular death ) and all-cause mortality . The relationship between combination therapy and cardiovascular events and all-cause mortality was assessed using Cox proportional hazards regression models to calculate hazards ratios ( HRs ) with a 95 % CI . Both covariate and propensity score adjusting methods were used to reduce confounding by indication . RESULTS A combination of aspirin , a statin , and ≥1 BP-lowering agent(s ) was used by 67 % of the patients . During a median of 5.0 years ( interquartile range 2.4 - 10.2 years ) , 347 vascular events occurred and 162 patients died . Combination therapy with aspirin , statin , and ≥1 BP-lowering agent was associated with a lower risk of myocardial infa rct ion ( HR 0.68 , 95 % CI 0.49 - 0.96 ) , ischemic cerebrovascular accident ( HR 0.37 , 95 % CI 0.16 - 0.84 ) , composite vascular end point ( HR 0.66 , 95 % CI 0.49 - 0.88 ) , vascular mortality ( HR 0.53 , 95 % CI 0.33 - 0.85 ) , and all-cause mortality ( HR 0.69 , 95 % CI 0.49 - 0.96 ) compared with the absence of combination therapy , after adjusting for confounding covariates in a propensity score . The use of 1 or only 2 components of combination therapy was associated with a higher risk for cardiovascular events compared with the combined use of aspirin , a statin , and ≥1 BP-lowering agent(s ) . CONCLUSION Two-thirds of the patients with CAD use a combination of aspirin , a statin , and ≥1 BP-lowering agent(s ) , components of a cardiovascular fixed-dose combination pill . Combination therapy with these agents is associated with a lower risk of vascular events and total mortality . Although treatment effect in observational studies should be interpreted with caution , the results of this study support supposed benefits from combination therapy . However , the effect of fixed-dose combination pill on clinical outcome needs to be demonstrated in r and omized clinical trials The pill burden of patients with hypertension and dyslipidemia can result in poor medication compliance . This study aim ed to evaluate the efficacy and safety of fixed-dose combination ( FDC ) therapy with olmesartan medoxomil ( 40 mg ) and rosuvastatin ( 20 mg ) in Korean patients with mild to moderate hypertension and dyslipidemia . This multicenter , r and omized , double-blind , factorial- design study included patients aged ≥20 years with mild to moderate essential hypertension and dyslipidemia . Patients were r and omly assigned to receive FDC therapy ( 40 mg olmesartan medoxomil , 20 mg rosuvastatin ) , 40 mg olmesartan medoxomil , 20 mg rosuvastatin , or a placebo . The percentage change from baseline in low-density lipoprotein cholesterol levels was compared between FDC therapy and olmesartan medoxomil , and the change from baseline in diastolic blood pressure was compared between FDC therapy and rosuvastatin 8 weeks after treatment . A total of 162 patients were included . The least square mean percentage change ( st and ard error ) from baseline in low-density lipoprotein cholesterol levels 8 weeks after treatment was significantly greater in the FDC than in the olmesartan medoxomil group ( −52.3 % [ 2.8 % ] vs −0.6 % [ 3.5 % ] , P<0.0001 ) , and the difference was −51.7 % ( 4.1 % ) ( 95 % confidence interval : −59.8 % to −43.6 % ) . The least square mean change ( st and ard error ) from baseline in diastolic blood pressure 8 weeks after treatment was significantly greater in the FDC group than in the rosuvastatin group ( −10.4 [ 1.2 ] mmHg vs 0.1 [ 1.6 ] mmHg , P<0.0001 ) , and the difference was −10.5 ( 1.8 ) mmHg ( 95 % confidence interval : −14.1 to −6.9 mmHg ) . There were 50 adverse events in 41 patients ( 22.7 % ) and eight adverse drug reactions in five patients ( 2.8 % ) . The study found that FDC therapy with olmesartan medoxomil and rosuvastatin is an effective , safe treatment for patients with hypertension and dyslipidemia . This combination may improve medication compliance in patients with a large pill burden Background : Notwithst and ing improving rates of hypertension control in North America , management of patients with both hypertension and dyslipidemia remains problematic . Based on evidence of improved control utilizing a simplified algorithm for management of hypertension ( STITCH ) , we question ed whether a simplified comprehensive treatment algorithm featuring initial use of single-pill combinations ( SPCs ) would improve management of participants with both hypertension and dyslipidemia . Method : We r and omized 35 primary care practice s in Ontario to either Guidelines -care (  following current Canadian guidelines ) or STITCH2-care ( following a treatment algorithm featuring SPCs ) . Practice s each enrolled up to 50 participants with at least one risk factor above target at entry based on Canadian guidelines for BP and LDL-cholesterol control . The primary endpoint was achieving targets for both hypertension and dyslipidemia control after 6 months , assessed at the practice level . Results : The primary endpoint was achieved in 31. 
    Output:
    