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 The ODYSSEY COMBO I study ( http:// clinical trials.gov/show/NCT01644175 ) evaluated efficacy and safety of alirocumab as add-on therapy to stable maximally tolerated daily statin with or without other lipid-lowering therapy in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia . METHODS This multicenter , phase 3 , r and omized ( 2:1 alirocumab vs placebo ) , double-blind , 52-week trial enrolled 316 patients with established coronary heart disease or coronary heart disease risk equivalents and hypercholesterolemia .  Alirocumab ( 75 mg every 2 weeks [ Q2W ] ) or placebo Q2W was self-administered subcutaneously via 1 mL prefilled pen . The alirocumab dose was increased to 150 mg Q2W ( also 1 mL ) at week 12 if week 8 low-density lipoprotein cholesterol ( LDL-C ) was ≥70 mg/dL. The primary efficacy end point was percent change in LDL-C from baseline to week 24 ( intention-to-treat analysis ) . RESULTS At week 24 , estimated mean ( 95 % CI ) changes in LDL-C from baseline were -48.2 % ( -52.0 % to -44.4 % ) and -2.3 % ( -7.6 % to 3.1 % ) for alirocumab and placebo , respectively , an estimated mean ( 95 % CI ) difference of -45.9 % ( -52.5 % to -39.3 % ) ( P < .0001 ) . Low-density lipoprotein cholesterol < 70 mg/dL was achieved by 75 % alirocumab versus 9 % placebo patients at week 24 . At week 12 , 83.2 % of evaluable alirocumab-treated patients remained on 75-mg Q2W . Treatment-emergent adverse events were comparable between groups . CONCLUSIONS Alirocumab treatment achieved a significantly greater reduction in LDL-C and allowed a greater proportion of patients to achieve LDL-C goals , versus placebo after 24 weeks in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia at baseline despite receiving maximally tolerated statin with or without other lipid-lowering therapy . The frequency of treatment-emergent adverse events and study medication discontinuations were generally comparable between treatment groups Aims To compare the efficacy [ low-density lipoprotein cholesterol ( LDL-C ) lowering ] and safety of alirocumab , a fully human monoclonal antibody to proprotein convertase subtilisin/kexin 9 , compared with ezetimibe , as add-on therapy to maximally tolerated statin therapy in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia . Methods and results COMBO II is a double-blind , double-dummy , active-controlled , parallel-group , 104-week study of alirocumab vs. ezetimibe .  Patients ( n = 720 ) with high cardiovascular risk and elevated LDL-C despite maximal doses of statins were enrolled ( August 2012–May 2013 ) . This pre-specified analysis was conducted after the last patient completed 52 weeks . Patients were r and omized to subcutaneous alirocumab 75 mg every 2 weeks ( plus oral placebo ) or oral ezetimibe 10 mg daily ( plus subcutaneous placebo ) on a background of statin therapy . At Week 24 , mean ± SE reductions in LDL-C from baseline were 50.6 ± 1.4 % for alirocumab vs. 20.7 ± 1.9 % for ezetimibe ( difference 29.8 ± 2.3 % ; P < 0.0001 ) ; 77.0 % of alirocumab and 45.6 % of ezetimibe patients achieved LDL-C < 1.8 mmol/L ( P < 0.0001 ) . Mean achieved LDL-C at Week 24 was 1.3 ± 0.04 mmol/L with alirocumab and 2.1 ± 0.05 mmol/L with ezetimibe , and were maintained to Week 52 . Alirocumab was generally well tolerated , with no evidence of an excess of treatment-emergent adverse events . Conclusion In patients at high cardiovascular risk with inadequately controlled LDL-C , alirocumab achieved significantly greater reductions in LDL-C compared with ezetimibe , with a similar safety profile . Trial registration clinical trials.gov Identifier : NCT01644188 Aim To evaluate the effect of alirocumab on frequency of st and ard apheresis treatments [ weekly or every 2 weeks ( Q2W ) ] in heterozygous familial hypercholesterolaemia ( HeFH ) . Methods and results ODYSSEY ESCAPE ( NCT02326220 ) was a double-blind study in 62 HeFH patients undergoing regular weekly or Q2W lipoprotein apheresis .  Patients were r and omly assigned ( 2:1 , respectively ) to receive alirocumab 150 mg ( n = 41 ) or placebo ( n = 21 ) Q2W subcutaneously for 18 weeks . From day 1 to week 6 , apheresis rate was fixed according to the patient ’s established schedule ; from weeks 7 to 18 , apheresis rate was adjusted based on the patient ’s low-density lipoprotein cholesterol ( LDL-C ) response in a blinded fashion . Apheresis was not performed when the LDL-C value was ≥30 % lower than the baseline ( pre-apheresis ) value . The primary efficacy endpoint was the rate of apheresis treatments over 12 weeks ( weeks 7–18 ) , st and ardized to number of planned treatments . In the alirocumab group the least square ( LS ) mean ± SE ( 95 % confidence interval [ CI ] ) per cent change in pre-apheresis LDL-C from baseline at week 6 was −53.7 ± 2.3 ( −58.2 to − 49.2 ) compared with 1.6 ± 3.1 ( –4.7 to 7.9 ) in the placebo group . The primary efficacy endpoint showed statistically significant benefit in favour of alirocumab ( Hodges – Lehmann median estimate of treatment difference : 0.75 ; 95 % CI 0.67–0.83 ; P < 0.0001 ) . Therefore , alirocumab-treated patients had a 0.75 ( 75 % ) additional reduction in the st and ardized rate of apheresis treatments vs. placebo-treated patients . During this period , 63.4 % of patients on alirocumab avoided all and 92.7 % avoided at least half of the apheresis treatments . Adverse event rates were similar ( 75.6 % of patients on alirocumab vs. 76.2 % on placebo ) . Conclusions Lipoprotein apheresis was discontinued in 63.4 % of patients on alirocumab who were previously undergoing regular apheresis , and the rate was at least halved in 92.7 % of patients . Alirocumab was generally safe and well tolerated Purpose Even with statins and other lipid-lowering therapy ( LLT ) , many patients with heterozygous familial hypercholesterolemia ( heFH ) continue to have elevated low-density lipoprotein cholesterol ( LDL-C ) levels . ODYSSEY HIGH FH ( NCT01617655 ) assessed the efficacy and safety of alirocumab , a proprotein convertase subtilisin/kexin type 9 monoclonal antibody , versus placebo in patients with heFH and LDL-C ≥ 160 mg/dl despite maximally tolerated statin ± other LLT . Methods Patients were r and omized to subcutaneous alirocumab 150 mg or placebo every 2 weeks ( Q2W ) for 78 weeks . The primary endpoint was percent change in LDL-C from baseline to week 24 . Results Mean baseline LDL-C levels were 196.3 mg/dl in the alirocumab ( n = 71 ) and 201.0 mg/dl in the placebo groups ( n = 35 ) . Significant mean ( st and ard error [ SE ] ) reductions in LDL-C from baseline to week 24 were observed with alirocumab ( −45.7 [ 3.5 ] % ) versus placebo ( −6.6 [ 4.9 ] % ) , a difference of −39.1 ( 6.0 ) % ( P < 0.0001 ) . Absolute mean ( SE ) LDL-C levels were reduced from baseline by 90.8 ( 6.7 ) mg/dl with alirocumab at week 24 , with reductions maintained to week 78 . Treatment-emergent adverse events were generally comparable between groups . Injection-site reactions were more frequent in the alirocumab group ( 8.3 % ) versus placebo ( 5.7 % ) ; most were mild in severity and did not result in study medication discontinuation . Conclusions In patients with heFH and very high LDL-C baseline levels despite maximally tolerated statin ± other LLT , alirocumab 150 mg Q2W demonstrated significant reductions in LDL-C levels with 41 % of patients achieving predefined LDL-C goals . Alirocumab was generally well tolerated BACKGROUND YUKAWA is a 12-week , r and omized , double-blind , placebo-controlled , phase 2 study evaluating the efficacy and safety of evolocumab ( AMG 145 ) in statin-treated Japanese patients at high cardiovascular risk . METHODS AND RESULTS 310 eligible patients receiving stable statin ( ±ezetimibe ) therapy were r and omized to 1 of 6 treatments : placebo every 2 weeks ( Q2W ) or monthly ( QM ) , evolocumab 70 mg or 140 mg Q2W , or evolocumab 280 mg or 420 mg QM . The primary endpoint was the percentage change from baseline in low-density lipoprotein cholesterol ( LDL-C ) measured by preparative ultracentrifugation ( UC ) . Secondary endpoints included percentage changes in other lipid parameters and the proportion of patients with LDL-C < 1.8 mmol/L.  Mean ( SD ) age was 62 ( 10 ) years ; 37 % were female ; and the mean ( SD ) baseline LDL-C was 3.7 ( 0.5 ) mmol/L ( by UC ) . Mean ( SE ) changes vs. placebo in LDL-C were greatest in the high-dose groups : -68.6 ( 3.0 ) % and -63.9 ( 3.2 ) % with 140 mg Q2W and 420 mg QM dosing , respectively . Up to 96 % of evolocumab-treated patients achieved LDL-C < 1.8 mmol/L. Adverse events ( AEs ) were more frequent in evolocumab ( 51 % ) vs. placebo ( 38 % ) patients ; 4 patients taking evolocumab discontinued treatment because of an AE . There were no significant differences in AE rates based on dose or dose frequency . CONCLUSIONS In Japanese patients at high cardiovascular risk with hypercholesterolemia on stable statin therapy , evolocumab  significantly reduced LDL-C and was well tolerated during this 12-week study Aims To assess long-term ( 78 weeks ) alirocumab treatment in patients with heterozygous familial hypercholesterolaemia ( HeFH ) and inadequate LDL-C control on maximally tolerated lipid-lowering therapy ( LLT ) . Methods and results In two r and omized , double-blind studies ( ODYSSEY FH I , n = 486 ; FH II , n = 249 ) , patients were r and omized 2 : 1 to alirocumab 75 mg or placebo every 2 weeks ( Q2W ) . Alirocumab dose was increased at Week 12 to 150 mg Q2W if Week 8 LDL-C was ≥1.8 mmol/L ( 70 mg/dL ) . Primary endpoint ( both studies ) was percentage change in calculated LDL-C from baseline to Week 24 . Mean LDL-C levels decreased from 3.7 mmol/L ( 144.7 mg/dL ) at baseline to 1.8 mmol/L ( 71.3 mg/dL ; −57.9 % vs. placebo ) at Week 24 in patients r and omized to alirocumab in FH I and from 3.5 mmol/L ( 134.6 mg/dL ) to 1.8 mmol/L ( 67.7 mg/dL ; −51.4 % vs. placebo ) in FH II ( P < 0.0001 ) . These reductions were maintained through Week 78 . LDL-C < 1.8 mmol/L ( regardless of cardiovascular risk ) was achieved at Week 24 by 59.8 and 68.2 % of alirocumab-treated patients in FH I and FH II , respectively . Adverse events result ed in discontinuation in 
    Output:
    
agent
The reduction in MACEs was observed in White but not in Asian subjects .
Both alirocumab and evolocumab are well tolerated and can greatly improve lipid profiles for patients at high cardiovascular risk .
Both PCSK9 monoclonal antibodies significantly reduce the risk of nonfatal MACEs in patients with previous cardiovascular events , but the effect on all-cause mortality remains uncertain
***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 The ODYSSEY COMBO I study ( http:// clinical trials.gov/show/NCT01644175 ) evaluated efficacy and safety of alirocumab as add-on therapy to stable maximally tolerated daily statin with or without other lipid-lowering therapy in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia . METHODS This multicenter , phase 3 , r and omized ( 2:1 alirocumab vs placebo ) , double-blind , 52-week trial enrolled 316 patients with established coronary heart disease or coronary heart disease risk equivalents and hypercholesterolemia .  Alirocumab ( 75 mg every 2 weeks [ Q2W ] ) or placebo Q2W was self-administered subcutaneously via 1 mL prefilled pen . The alirocumab dose was increased to 150 mg Q2W ( also 1 mL ) at week 12 if week 8 low-density lipoprotein cholesterol ( LDL-C ) was ≥70 mg/dL. The primary efficacy end point was percent change in LDL-C from baseline to week 24 ( intention-to-treat analysis ) . RESULTS At week 24 , estimated mean ( 95 % CI ) changes in LDL-C from baseline were -48.2 % ( -52.0 % to -44.4 % ) and -2.3 % ( -7.6 % to 3.1 % ) for alirocumab and placebo , respectively , an estimated mean ( 95 % CI ) difference of -45.9 % ( -52.5 % to -39.3 % ) ( P < .0001 ) . Low-density lipoprotein cholesterol < 70 mg/dL was achieved by 75 % alirocumab versus 9 % placebo patients at week 24 . At week 12 , 83.2 % of evaluable alirocumab-treated patients remained on 75-mg Q2W . Treatment-emergent adverse events were comparable between groups . CONCLUSIONS Alirocumab treatment achieved a significantly greater reduction in LDL-C and allowed a greater proportion of patients to achieve LDL-C goals , versus placebo after 24 weeks in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia at baseline despite receiving maximally tolerated statin with or without other lipid-lowering therapy . The frequency of treatment-emergent adverse events and study medication discontinuations were generally comparable between treatment groups Aims To compare the efficacy [ low-density lipoprotein cholesterol ( LDL-C ) lowering ] and safety of alirocumab , a fully human monoclonal antibody to proprotein convertase subtilisin/kexin 9 , compared with ezetimibe , as add-on therapy to maximally tolerated statin therapy in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia . Methods and results COMBO II is a double-blind , double-dummy , active-controlled , parallel-group , 104-week study of alirocumab vs. ezetimibe .  Patients ( n = 720 ) with high cardiovascular risk and elevated LDL-C despite maximal doses of statins were enrolled ( August 2012–May 2013 ) . This pre-specified analysis was conducted after the last patient completed 52 weeks . Patients were r and omized to subcutaneous alirocumab 75 mg every 2 weeks ( plus oral placebo ) or oral ezetimibe 10 mg daily ( plus subcutaneous placebo ) on a background of statin therapy . At Week 24 , mean ± SE reductions in LDL-C from baseline were 50.6 ± 1.4 % for alirocumab vs. 20.7 ± 1.9 % for ezetimibe ( difference 29.8 ± 2.3 % ; P < 0.0001 ) ; 77.0 % of alirocumab and 45.6 % of ezetimibe patients achieved LDL-C < 1.8 mmol/L ( P < 0.0001 ) . Mean achieved LDL-C at Week 24 was 1.3 ± 0.04 mmol/L with alirocumab and 2.1 ± 0.05 mmol/L with ezetimibe , and were maintained to Week 52 . Alirocumab was generally well tolerated , with no evidence of an excess of treatment-emergent adverse events . Conclusion In patients at high cardiovascular risk with inadequately controlled LDL-C , alirocumab achieved significantly greater reductions in LDL-C compared with ezetimibe , with a similar safety profile . Trial registration clinical trials.gov Identifier : NCT01644188 Aim To evaluate the effect of alirocumab on frequency of st and ard apheresis treatments [ weekly or every 2 weeks ( Q2W ) ] in heterozygous familial hypercholesterolaemia ( HeFH ) . Methods and results ODYSSEY ESCAPE ( NCT02326220 ) was a double-blind study in 62 HeFH patients undergoing regular weekly or Q2W lipoprotein apheresis .  Patients were r and omly assigned ( 2:1 , respectively ) to receive alirocumab 150 mg ( n = 41 ) or placebo ( n = 21 ) Q2W subcutaneously for 18 weeks . From day 1 to week 6 , apheresis rate was fixed according to the patient ’s established schedule ; from weeks 7 to 18 , apheresis rate was adjusted based on the patient ’s low-density lipoprotein cholesterol ( LDL-C ) response in a blinded fashion . Apheresis was not performed when the LDL-C value was ≥30 % lower than the baseline ( pre-apheresis ) value . The primary efficacy endpoint was the rate of apheresis treatments over 12 weeks ( weeks 7–18 ) , st and ardized to number of planned treatments . In the alirocumab group the least square ( LS ) mean ± SE ( 95 % confidence interval [ CI ] ) per cent change in pre-apheresis LDL-C from baseline at week 6 was −53.7 ± 2.3 ( −58.2 to − 49.2 ) compared with 1.6 ± 3.1 ( –4.7 to 7.9 ) in the placebo group . The primary efficacy endpoint showed statistically significant benefit in favour of alirocumab ( Hodges – Lehmann median estimate of treatment difference : 0.75 ; 95 % CI 0.67–0.83 ; P < 0.0001 ) . Therefore , alirocumab-treated patients had a 0.75 ( 75 % ) additional reduction in the st and ardized rate of apheresis treatments vs. placebo-treated patients . During this period , 63.4 % of patients on alirocumab avoided all and 92.7 % avoided at least half of the apheresis treatments . Adverse event rates were similar ( 75.6 % of patients on alirocumab vs. 76.2 % on placebo ) . Conclusions Lipoprotein apheresis was discontinued in 63.4 % of patients on alirocumab who were previously undergoing regular apheresis , and the rate was at least halved in 92.7 % of patients . Alirocumab was generally safe and well tolerated Purpose Even with statins and other lipid-lowering therapy ( LLT ) , many patients with heterozygous familial hypercholesterolemia ( heFH ) continue to have elevated low-density lipoprotein cholesterol ( LDL-C ) levels . ODYSSEY HIGH FH ( NCT01617655 ) assessed the efficacy and safety of alirocumab , a proprotein convertase subtilisin/kexin type 9 monoclonal antibody , versus placebo in patients with heFH and LDL-C ≥ 160 mg/dl despite maximally tolerated statin ± other LLT . Methods Patients were r and omized to subcutaneous alirocumab 150 mg or placebo every 2 weeks ( Q2W ) for 78 weeks . The primary endpoint was percent change in LDL-C from baseline to week 24 . Results Mean baseline LDL-C levels were 196.3 mg/dl in the alirocumab ( n = 71 ) and 201.0 mg/dl in the placebo groups ( n = 35 ) . Significant mean ( st and ard error [ SE ] ) reductions in LDL-C from baseline to week 24 were observed with alirocumab ( −45.7 [ 3.5 ] % ) versus placebo ( −6.6 [ 4.9 ] % ) , a difference of −39.1 ( 6.0 ) % ( P < 0.0001 ) . Absolute mean ( SE ) LDL-C levels were reduced from baseline by 90.8 ( 6.7 ) mg/dl with alirocumab at week 24 , with reductions maintained to week 78 . Treatment-emergent adverse events were generally comparable between groups . Injection-site reactions were more frequent in the alirocumab group ( 8.3 % ) versus placebo ( 5.7 % ) ; most were mild in severity and did not result in study medication discontinuation . Conclusions In patients with heFH and very high LDL-C baseline levels despite maximally tolerated statin ± other LLT , alirocumab 150 mg Q2W demonstrated significant reductions in LDL-C levels with 41 % of patients achieving predefined LDL-C goals . Alirocumab was generally well tolerated BACKGROUND YUKAWA is a 12-week , r and omized , double-blind , placebo-controlled , phase 2 study evaluating the efficacy and safety of evolocumab ( AMG 145 ) in statin-treated Japanese patients at high cardiovascular risk . METHODS AND RESULTS 310 eligible patients receiving stable statin ( ±ezetimibe ) therapy were r and omized to 1 of 6 treatments : placebo every 2 weeks ( Q2W ) or monthly ( QM ) , evolocumab 70 mg or 140 mg Q2W , or evolocumab 280 mg or 420 mg QM . The primary endpoint was the percentage change from baseline in low-density lipoprotein cholesterol ( LDL-C ) measured by preparative ultracentrifugation ( UC ) . Secondary endpoints included percentage changes in other lipid parameters and the proportion of patients with LDL-C < 1.8 mmol/L.  Mean ( SD ) age was 62 ( 10 ) years ; 37 % were female ; and the mean ( SD ) baseline LDL-C was 3.7 ( 0.5 ) mmol/L ( by UC ) . Mean ( SE ) changes vs. placebo in LDL-C were greatest in the high-dose groups : -68.6 ( 3.0 ) % and -63.9 ( 3.2 ) % with 140 mg Q2W and 420 mg QM dosing , respectively . Up to 96 % of evolocumab-treated patients achieved LDL-C < 1.8 mmol/L. Adverse events ( AEs ) were more frequent in evolocumab ( 51 % ) vs. placebo ( 38 % ) patients ; 4 patients taking evolocumab discontinued treatment because of an AE . There were no significant differences in AE rates based on dose or dose frequency . CONCLUSIONS In Japanese patients at high cardiovascular risk with hypercholesterolemia on stable statin therapy , evolocumab  significantly reduced LDL-C and was well tolerated during this 12-week study Aims To assess long-term ( 78 weeks ) alirocumab treatment in patients with heterozygous familial hypercholesterolaemia ( HeFH ) and inadequate LDL-C control on maximally tolerated lipid-lowering therapy ( LLT ) . Methods and results In two r and omized , double-blind studies ( ODYSSEY FH I , n = 486 ; FH II , n = 249 ) , patients were r and omized 2 : 1 to alirocumab 75 mg or placebo every 2 weeks ( Q2W ) . Alirocumab dose was increased at Week 12 to 150 mg Q2W if Week 8 LDL-C was ≥1.8 mmol/L ( 70 mg/dL ) . Primary endpoint ( both studies ) was percentage change in calculated LDL-C from baseline to Week 24 . Mean LDL-C levels decreased from 3.7 mmol/L ( 144.7 mg/dL ) at baseline to 1.8 mmol/L ( 71.3 mg/dL ; −57.9 % vs. placebo ) at Week 24 in patients r and omized to alirocumab in FH I and from 3.5 mmol/L ( 134.6 mg/dL ) to 1.8 mmol/L ( 67.7 mg/dL ; −51.4 % vs. placebo ) in FH II ( P < 0.0001 ) . These reductions were maintained through Week 78 . LDL-C < 1.8 mmol/L ( regardless of cardiovascular risk ) was achieved at Week 24 by 59.8 and 68.2 % of alirocumab-treated patients in FH I and FH II , respectively . Adverse events result ed in discontinuation in 
    Output:
    