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: Elevated lipoprotein(a ) [ Lp(a ) ] is independently associated with increased cardiovascular risk . However , treatment options for elevated Lp(a ) are limited . Alirocumab , a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 , reduced low-density lipoprotein cholesterol ( LDL-C ) by up to 62 % from baseline in phase 3 studies , with adverse event rates similar between alirocumab and controls . We evaluated the effect of alirocumab on serum Lp(a ) using pooled data from the phase 3 ODYSSEY program : 4,915 patients with hypercholesterolemia from 10 phase 3 studies were included . Eight studies evaluated alirocumab 75 mg every 2 weeks ( Q2W ) , with possible increase to 150 mg Q2W at week 12 depending on LDL-C at week 8 ( 75/150 mg Q2W ) ; the other 2 studies evaluated alirocumab 150-mg Q2W from the outset . Comparators were placebo or ezetimibe . Eight studies were conducted on a background of statins , and 2 studies were carried out with no statins . Alirocumab was associated with significant reductions in Lp(a ) , regardless of starting dose and use of concomitant statins . At week 24 , reductions from baseline were 23 % to 27 % with alirocumab 75/150-mg Q2W and 29 % with alirocumab 150-mg Q2W ( all comparisons p < 0.0001 vs controls ) . Reductions were sustained over 78 to 104 weeks . Lp(a ) reductions with alirocumab were independent of race , gender , presence of familial hypercholesterolemia , baseline Lp(a ) , and LDL-C concentrations , or use of statins . In conclusion , in addition to marked reduction in LDL-C , alirocumab leads to a significant and sustained lowering of Lp(a ) Background Ezetimibe , as a cholesterol absorption inhibitor , has been shown protecting against atherosclerosis when combined with statin . However , side by side comparison has not been made to evaluate the beneficial effects of ezetimibe alone versus statin . Herein , the study aim ed to test whether ezetimibe alone would exhibit similar effects as statin and the combination therapy would be necessary in a moderate lesion size . Methods and Results ApoE-/- male mice that were fed a saturated-fat supplemented diet were r and omly assigned to different therapeutic regimens : vehicle , ezetimibe alone ( 10 mg/kg/day ) , atorvastatin ( 20 mg/kg/day ) or combination of ezetimibe and atorvastatin through the drinking water . On 28 days , mice were sacrificed and aorta and sera were collected to analyze the atherosclerotic lesion and blood lipid and cholesterol levels . As a result , ezetimibe alone exerted similar protective effects on atherosclerotic lesion sizes as atorvastatin , which was mediated by lowering serum cholesterol concentrations , inhibiting macrophage accumulation in the lesions and reducing circulatory inflammatory cytokines , such as monocyte chemoattractant protein ( MCP-1 ) and tumor necrosis factor ( TNF-α ) . In contrast to ezetimibe administration , atorvastatin alone attenuated atherosclerotic lesion which is dependent on its anti-inflammation effects . There were no significance differences in lesion areas and serum concentrations of cholesterol , oxidized LDL and inflammatory cytokines between combination therapy and monotherapy ( either ezetimibe or atorvastatin ) . There were significant correlations between the lesion areas and serum concentrations of cholesterol , MCP-1 and TNF-α , respectively . However , there were no significant correlations between the lesion areas and serum concentrations of TGF-β1 and oxLDL . Conclusions Ezetimibe alone played the same protection against a moderate atherosclerotic lesion as atorvastatin , which was associated with lowering serum cholesterol , decreasing circulating inflammatory cytokines , and inhibiting macrophage accumulation in the lesions Ezetimibe , a cholesterol absorption inhibitor , can be combined with statins to lower LDL-cholesterol . We evaluated additional ezetimibe ( 10 mg/day ) in a placebo-controlled , double blind , r and omized cross-over study in 20 patients ( age 56+/-9 years , m : f 10:10 , BMI 27.5+/-4.0 kg/m(2 ) ) suffering from severe hypercholesterolemia and CHD who were treated by statins and regular LDL-apheresis .  Lipoproteins ( cholesterol , triglycerides , LDL-cholesterol , HDL-cholesterol , VLDL-cholesterol , VLDL-triglycerides , lipoprotein(a ) ) were determined twice ( before and during ezetimibe/placebo , each given for 5 weeks ) , dietary behaviour was analyzed once ( 3-days- protocol ) during each treatment period . During ezetimibe the mean ( + /-S.D. ) preapheresis LDL-cholesterol concentration decreased from 159+/-26 mg/dl ( 4.11+/-0.67 mmol/l ) to 133+/-28 mg/dl ( 3.44+/-0.72 mmol/l ) ( -16+/-11 % , P<0.0001 , Wilcoxon test ) and the postapheresis LDL-cholesterol from 51+/-9 mg/dl ( 1.32+/-0.23 mmol/l ) to 43+/-8 mg/dl ( 1.11+/-0.21 mmol/l ) ( -14+/-25 % , P<0.05 ) , while there was no significant change during placebo .  Mean VLDL-cholesterol fell by 18+/-71 % ( P<0.05 ) during ezetimibe and was not significantly changed by placebo ( + 19+/-70 % ) . Furthermore , during ezetimibe less plasma volume was treated ( 3725+/-1560 versus 3870+/-1549 ml , P<0.05 ) . Ezetimibe had no effect on pre- and postapheresis triglyceride , HDL-cholesterol and lipoprotein(a ) levels . The effect of ezetimibe was independent of the statin dose . Dietary behaviour did not change and no side effects were observed . Thus , in patients with severe LDL-hypercholesterolemia and CHD the addition of ezetimibe to intensive lipid lowering therapy ( statins and LDL-apheresis ) result ed in a further , clinical ly significant decrease of LDL-cholesterol Background —Despite the established efficacy of statins , many patients do not achieve recommended LDL cholesterol ( LDL-C ) goals . Contributing factors may be inadequate dosing , increased risk for adverse effects with high-dose monotherapy , and increased potential for intolerance and adverse effects with combinations of available agents . Methods and Results —In a double-blind study , 628 patients with baseline LDL-C 145 to 250 mg/dL and triglycerides ≤350 mg/dL were r and omly assigned to receive 1 of the following for 12 weeks : ezetimibe ( 10 mg/d ) ; atorvastatin ( 10 , 20 , 40 , or 80 mg/d ) ; ezetimibe ( 10 mg ) plus atorvastatin ( 10 , 20 , 40 , or 80 mg/d ) ; or placebo . The primary efficacy end point was percentage reduction in LDL-C for pooled ezetimibe plus atorvastatin versus pooled atorvastatin treatment groups . Ezetimibe plus atorvastatin significantly improved LDL-C , HDL cholesterol ( HDL-C ) , triglycerides , total cholesterol : HDL-C , and high-sensitivity C-reactive protein ( hs-CRP ) compared with atorvastatin alone ( P < 0.01 ) . Coadministration of ezetimibe provided a significant additional 12 % LDL-C reduction , 3 % HDL-C increase , 8 % triglyceride reduction , and 10 % hs-CRP reduction versus atorvastatin alone . Ezetimibe plus atorvastatin  provided LDL-C reductions of 50 % to 60 % , triglyceride reductions of 30 % to 40 % , and HDL-C increases of 5 % to 9 % , depending on atorvastatin dose . LDL-C reductions with ezetimibe plus 10 mg atorvastatin ( 50 % ) and 80 mg atorvastatin alone ( 51 % ) were similar . Conclusions —Ezetimibe plus atorvastatin was well tolerated , with a safety profile similar to atorvastatin alone and to placebo . When coadministered with atorvastatin , ezetimibe provided significant incremental reductions in LDL-C and triglycerides and increases in HDL-C. Coadministration of ezetimibe and atorvastatin offers a well-tolerated and highly efficacious new treatment option for patients with hypercholesterolemia International guidelines recommend lower target cholesterol levels and treatment of low high-density lipoprotein cholesterol ( HDL-C ) and elevated triglycerides for patients at moderately high to high coronary heart disease ( CHD ) risk . Combination therapy is often required to achieve multiple lipid treatment goals , and > or = 50 % reduction in low-density lipoprotein cholesterol ( LDL-C ) is needed in some patients to achieve aggressive LDL-C targets . In this context , we evaluated comparative effects on lipid levels of combination therapy at low to moderate doses with a statin plus extended-release niacin ( niacin ER ) , a statin plus ezetimibe , and a highly potent statin alone . This was an open-label , multicenter , 12-week study in 292 patients ( 50 % women ) who qualified for drug therapy based on number of CHD risk factors . Patients were r and omized to four parallel arms , titrated from low to moderate or high doses : atorvastatin/niacin ER , rosuvastatin/niacin ER , simvastatin/ezetimibe , or rosuvastatin alone . Baseline mean values were , for LDL-C 197 mg/dL ( 5.1 mmol/L ) , HDL-C 49 mg/dL ( 1.3 mmol/L ) , triglycerides 168 mg/dL ( 1.9 mmol/L ) . There were no significant differences among treatment groups in the change from baseline in LDL-C at pre-specified timepoints during treatment . All groups lowered LDL-C by approximately 50 % or more ( range -49 to -57 % ) , achieving mean levels of 82 - 98 mg/dL ( 2.1 - 2.5 mmol/L ) . Changes in non-HDL-C ( range -46 to -55 % ) mirrored those for LDL-C and did not differ among treatment groups . Statin/niacin ER combination regimens also increased HDL-C and large HDL ( HDL2 ) and lowered triglycerides and lipoprotein ( a ) significantly more than other regimens . No drug-related myopathy or hepatotoxicity was observed . In this study , low to moderate dose combination therapy with a statin and niacin ER provided broad control of lipids and lipoproteins independently associated with CHD BACKGROUND Ezetimibe ( SCH 58235 ) is a novel cholesterol absorption inhibitor that selectively and potently blocks intestinal absorption of dietary and biliary cholesterol . OBJECTIVE Data from 2 multicenter , placebo-controlled , double-blind , r and omized , parallel-group , 12-week studies of ezetimibe were pooled to evaluate the drug 's effect on lipid parameters in patients with primary hypercholesterolemia . METHODS After dietary stabilization ( National Cholesterol Education Program Step I diet or a stricter diet ) , washout of lipid-altering drugs , and a 6-week placebo lead-in period , patients with baseline plasma low-density lipoprotein cholesterol ( LDL-C ) levels > or = 130 and < or = 250 mg/dL and plasma triglyceride ( TG ) levels < or = 300 mg/dL were r and omized to receive either ezetimibe 0.25 , 1 , 5 , or 10 mg , or placebo administered once daily before the morning meal in study A ( dose-response study ) or ezetimibe 5 or 10 mg or placebo administered once daily before the morning meal or at bedtime in study B ( dose-regimen study ) . RESULTS A total of 432 patients were included in this pooled analysis , 243 in study A and 189 in study B. The 5- and 10-mg doses of ezetimibe significantly reduced LDL-C levels by 15.7 % and 18.5 % , respectively ( P < 0.01 vs placebo ) and significantly increased high-density lipoprotein cholesterol ( hDL-C ) levels by 2.9 % and 3.5 
    Output:
    
agent
Conclusions Ezetimibe monotherapy ( 10 mg/day ) showed a small ( 7.06 % ) but statistically significant reduction in the plasma levels of Lp(a ) in patients with primary hypercholesterolemia .
According to current literature , this magnitude of reduction seems to have no clinical relevance .
***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: Elevated lipoprotein(a ) [ Lp(a ) ] is independently associated with increased cardiovascular risk . However , treatment options for elevated Lp(a ) are limited . Alirocumab , a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 , reduced low-density lipoprotein cholesterol ( LDL-C ) by up to 62 % from baseline in phase 3 studies , with adverse event rates similar between alirocumab and controls . We evaluated the effect of alirocumab on serum Lp(a ) using pooled data from the phase 3 ODYSSEY program : 4,915 patients with hypercholesterolemia from 10 phase 3 studies were included . Eight studies evaluated alirocumab 75 mg every 2 weeks ( Q2W ) , with possible increase to 150 mg Q2W at week 12 depending on LDL-C at week 8 ( 75/150 mg Q2W ) ; the other 2 studies evaluated alirocumab 150-mg Q2W from the outset . Comparators were placebo or ezetimibe . Eight studies were conducted on a background of statins , and 2 studies were carried out with no statins . Alirocumab was associated with significant reductions in Lp(a ) , regardless of starting dose and use of concomitant statins . At week 24 , reductions from baseline were 23 % to 27 % with alirocumab 75/150-mg Q2W and 29 % with alirocumab 150-mg Q2W ( all comparisons p < 0.0001 vs controls ) . Reductions were sustained over 78 to 104 weeks . Lp(a ) reductions with alirocumab were independent of race , gender , presence of familial hypercholesterolemia , baseline Lp(a ) , and LDL-C concentrations , or use of statins . In conclusion , in addition to marked reduction in LDL-C , alirocumab leads to a significant and sustained lowering of Lp(a ) Background Ezetimibe , as a cholesterol absorption inhibitor , has been shown protecting against atherosclerosis when combined with statin . However , side by side comparison has not been made to evaluate the beneficial effects of ezetimibe alone versus statin . Herein , the study aim ed to test whether ezetimibe alone would exhibit similar effects as statin and the combination therapy would be necessary in a moderate lesion size . Methods and Results ApoE-/- male mice that were fed a saturated-fat supplemented diet were r and omly assigned to different therapeutic regimens : vehicle , ezetimibe alone ( 10 mg/kg/day ) , atorvastatin ( 20 mg/kg/day ) or combination of ezetimibe and atorvastatin through the drinking water . On 28 days , mice were sacrificed and aorta and sera were collected to analyze the atherosclerotic lesion and blood lipid and cholesterol levels . As a result , ezetimibe alone exerted similar protective effects on atherosclerotic lesion sizes as atorvastatin , which was mediated by lowering serum cholesterol concentrations , inhibiting macrophage accumulation in the lesions and reducing circulatory inflammatory cytokines , such as monocyte chemoattractant protein ( MCP-1 ) and tumor necrosis factor ( TNF-α ) . In contrast to ezetimibe administration , atorvastatin alone attenuated atherosclerotic lesion which is dependent on its anti-inflammation effects . There were no significance differences in lesion areas and serum concentrations of cholesterol , oxidized LDL and inflammatory cytokines between combination therapy and monotherapy ( either ezetimibe or atorvastatin ) . There were significant correlations between the lesion areas and serum concentrations of cholesterol , MCP-1 and TNF-α , respectively . However , there were no significant correlations between the lesion areas and serum concentrations of TGF-β1 and oxLDL . Conclusions Ezetimibe alone played the same protection against a moderate atherosclerotic lesion as atorvastatin , which was associated with lowering serum cholesterol , decreasing circulating inflammatory cytokines , and inhibiting macrophage accumulation in the lesions Ezetimibe , a cholesterol absorption inhibitor , can be combined with statins to lower LDL-cholesterol . We evaluated additional ezetimibe ( 10 mg/day ) in a placebo-controlled , double blind , r and omized cross-over study in 20 patients ( age 56+/-9 years , m : f 10:10 , BMI 27.5+/-4.0 kg/m(2 ) ) suffering from severe hypercholesterolemia and CHD who were treated by statins and regular LDL-apheresis .  Lipoproteins ( cholesterol , triglycerides , LDL-cholesterol , HDL-cholesterol , VLDL-cholesterol , VLDL-triglycerides , lipoprotein(a ) ) were determined twice ( before and during ezetimibe/placebo , each given for 5 weeks ) , dietary behaviour was analyzed once ( 3-days- protocol ) during each treatment period . During ezetimibe the mean ( + /-S.D. ) preapheresis LDL-cholesterol concentration decreased from 159+/-26 mg/dl ( 4.11+/-0.67 mmol/l ) to 133+/-28 mg/dl ( 3.44+/-0.72 mmol/l ) ( -16+/-11 % , P<0.0001 , Wilcoxon test ) and the postapheresis LDL-cholesterol from 51+/-9 mg/dl ( 1.32+/-0.23 mmol/l ) to 43+/-8 mg/dl ( 1.11+/-0.21 mmol/l ) ( -14+/-25 % , P<0.05 ) , while there was no significant change during placebo .  Mean VLDL-cholesterol fell by 18+/-71 % ( P<0.05 ) during ezetimibe and was not significantly changed by placebo ( + 19+/-70 % ) . Furthermore , during ezetimibe less plasma volume was treated ( 3725+/-1560 versus 3870+/-1549 ml , P<0.05 ) . Ezetimibe had no effect on pre- and postapheresis triglyceride , HDL-cholesterol and lipoprotein(a ) levels . The effect of ezetimibe was independent of the statin dose . Dietary behaviour did not change and no side effects were observed . Thus , in patients with severe LDL-hypercholesterolemia and CHD the addition of ezetimibe to intensive lipid lowering therapy ( statins and LDL-apheresis ) result ed in a further , clinical ly significant decrease of LDL-cholesterol Background —Despite the established efficacy of statins , many patients do not achieve recommended LDL cholesterol ( LDL-C ) goals . Contributing factors may be inadequate dosing , increased risk for adverse effects with high-dose monotherapy , and increased potential for intolerance and adverse effects with combinations of available agents . Methods and Results —In a double-blind study , 628 patients with baseline LDL-C 145 to 250 mg/dL and triglycerides ≤350 mg/dL were r and omly assigned to receive 1 of the following for 12 weeks : ezetimibe ( 10 mg/d ) ; atorvastatin ( 10 , 20 , 40 , or 80 mg/d ) ; ezetimibe ( 10 mg ) plus atorvastatin ( 10 , 20 , 40 , or 80 mg/d ) ; or placebo . The primary efficacy end point was percentage reduction in LDL-C for pooled ezetimibe plus atorvastatin versus pooled atorvastatin treatment groups . Ezetimibe plus atorvastatin significantly improved LDL-C , HDL cholesterol ( HDL-C ) , triglycerides , total cholesterol : HDL-C , and high-sensitivity C-reactive protein ( hs-CRP ) compared with atorvastatin alone ( P < 0.01 ) . Coadministration of ezetimibe provided a significant additional 12 % LDL-C reduction , 3 % HDL-C increase , 8 % triglyceride reduction , and 10 % hs-CRP reduction versus atorvastatin alone . Ezetimibe plus atorvastatin  provided LDL-C reductions of 50 % to 60 % , triglyceride reductions of 30 % to 40 % , and HDL-C increases of 5 % to 9 % , depending on atorvastatin dose . LDL-C reductions with ezetimibe plus 10 mg atorvastatin ( 50 % ) and 80 mg atorvastatin alone ( 51 % ) were similar . Conclusions —Ezetimibe plus atorvastatin was well tolerated , with a safety profile similar to atorvastatin alone and to placebo . When coadministered with atorvastatin , ezetimibe provided significant incremental reductions in LDL-C and triglycerides and increases in HDL-C. Coadministration of ezetimibe and atorvastatin offers a well-tolerated and highly efficacious new treatment option for patients with hypercholesterolemia International guidelines recommend lower target cholesterol levels and treatment of low high-density lipoprotein cholesterol ( HDL-C ) and elevated triglycerides for patients at moderately high to high coronary heart disease ( CHD ) risk . Combination therapy is often required to achieve multiple lipid treatment goals , and > or = 50 % reduction in low-density lipoprotein cholesterol ( LDL-C ) is needed in some patients to achieve aggressive LDL-C targets . In this context , we evaluated comparative effects on lipid levels of combination therapy at low to moderate doses with a statin plus extended-release niacin ( niacin ER ) , a statin plus ezetimibe , and a highly potent statin alone . This was an open-label , multicenter , 12-week study in 292 patients ( 50 % women ) who qualified for drug therapy based on number of CHD risk factors . Patients were r and omized to four parallel arms , titrated from low to moderate or high doses : atorvastatin/niacin ER , rosuvastatin/niacin ER , simvastatin/ezetimibe , or rosuvastatin alone . Baseline mean values were , for LDL-C 197 mg/dL ( 5.1 mmol/L ) , HDL-C 49 mg/dL ( 1.3 mmol/L ) , triglycerides 168 mg/dL ( 1.9 mmol/L ) . There were no significant differences among treatment groups in the change from baseline in LDL-C at pre-specified timepoints during treatment . All groups lowered LDL-C by approximately 50 % or more ( range -49 to -57 % ) , achieving mean levels of 82 - 98 mg/dL ( 2.1 - 2.5 mmol/L ) . Changes in non-HDL-C ( range -46 to -55 % ) mirrored those for LDL-C and did not differ among treatment groups . Statin/niacin ER combination regimens also increased HDL-C and large HDL ( HDL2 ) and lowered triglycerides and lipoprotein ( a ) significantly more than other regimens . No drug-related myopathy or hepatotoxicity was observed . In this study , low to moderate dose combination therapy with a statin and niacin ER provided broad control of lipids and lipoproteins independently associated with CHD BACKGROUND Ezetimibe ( SCH 58235 ) is a novel cholesterol absorption inhibitor that selectively and potently blocks intestinal absorption of dietary and biliary cholesterol . OBJECTIVE Data from 2 multicenter , placebo-controlled , double-blind , r and omized , parallel-group , 12-week studies of ezetimibe were pooled to evaluate the drug 's effect on lipid parameters in patients with primary hypercholesterolemia . METHODS After dietary stabilization ( National Cholesterol Education Program Step I diet or a stricter diet ) , washout of lipid-altering drugs , and a 6-week placebo lead-in period , patients with baseline plasma low-density lipoprotein cholesterol ( LDL-C ) levels > or = 130 and < or = 250 mg/dL and plasma triglyceride ( TG ) levels < or = 300 mg/dL were r and omized to receive either ezetimibe 0.25 , 1 , 5 , or 10 mg , or placebo administered once daily before the morning meal in study A ( dose-response study ) or ezetimibe 5 or 10 mg or placebo administered once daily before the morning meal or at bedtime in study B ( dose-regimen study ) . RESULTS A total of 432 patients were included in this pooled analysis , 243 in study A and 189 in study B. The 5- and 10-mg doses of ezetimibe significantly reduced LDL-C levels by 15.7 % and 18.5 % , respectively ( P < 0.01 vs placebo ) and significantly increased high-density lipoprotein cholesterol ( hDL-C ) levels by 2.9 % and 3.5 
    Output:
    