Population Characteristics and Study Quality of Included Trials , by Combination Therapy Agent and Potency Comparison Long-Term Clinical Outcomes We found insufficient evidence to compare long-term clinical outcomes ( mortality , acute coronary events , cerebrovascular events , and revascularization procedures ) for all combination therapy and statin intensity comparisons .
Figure 1 presents an evidence map of studies that evaluated these
Atherosclerotic cardiovascular disease ( ASCVD ) affects more than 15 million Americans ( 1 ) and is the leading cause of death for both men and women in the United States ( 2 ) .
Trials have demonstrated reductions in low-density lipoprotein ( LDL ) cholesterol levels ( 3 ) and decreased ASCVD risk with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor ( statin ) monotherapy ( 4 ) .
Over the past decade , statins have often been used in combination with other lipid-modifying agents .
Recently , several high-profile r and omized , controlled trials ( RCTs ) have evaluated add-on therapy ( 57 ) , wherein statin monotherapy is compared with the combination of the same statin dose and another lipid-modifying agent .
Add-on combination therapy can lead to superior lipid outcomes , but studies have not shown decreased rates of cardiovascular death , myocardial infa rct ion , revascularization , or stroke ( 57 ) .
Therefore , the 2013 American College of Cardiology ( ACC ) and American Heart Association ( AHA ) guidelines recommend moderate- or high-intensity statin monotherapy as the first-line strategy for ASCVD risk reduction among patients with LDL cholesterol levels of 4.91 mmol/L or greater ( 190 mg/dL ) , preexisting ASCVD , diabetes mellitus ( DM ) , or estimated 10-year ASCVD risk of 7.5 % or greater ( 8) .
Adverse effects are more common with higher-intensity statin regimens ( 9 ) , and musculoskeletal adverse events occur frequently among patients with the C variant in the SLCO1B1 gene ( 10 ) .
The 2013 ACC/AHA guidelines suggest that clinicians consider moderated combination therapy with a lower-intensity statin and another lipid-modifying medication among high-risk patients ( LDL cholesterol level 4.91 mmol/L [ 190 mg/dL ] , preexisting ASCVD , or DM ) who are intolerant of or unresponsive to statins ( evidence grade E : expert opinion ) ( 8) .
Yet , it is unclear whether this strategy results in similar ASCVD risk reductions and fewer adverse effects compared with higher-intensity statin monotherapy .
A 2009 systematic review that examined these questions found insufficient evidence to weigh benefits and risks of moderated combination therapy ( 12 ) .
We aim ed to compare the effectiveness , safety , and tolerability of moderated combination therapy of statin with another lipid-modifying medication ( bile acid sequestrant , ezetimibe , fibrate , niacin , or -3 fatty acid ) with those of higher-intensity statin monotherapy among high-risk patients .
We sought to compare the long-term clinical benefits and short-term lipid effects of moderated combination therapy with those of higher-intensity statin monotherapy , as well as to determine whether these regimens differ in rates of adherence and harms .
Given the recent release of the 2013 ACC/AHA guidelines ( 8) , we narrowed the scope of this manuscript to focus on evidence most relevant to high-risk population s for whom combination therapy might be considered .
Prior studies have suggested schemes to group statins on the basis of their reported LDL cholesterol reduction ( 17 , 18 ) , which are similar to the strategy used by the ACC/AHA committee ( 8) .
Effects of Ezetimibe/Simvastatin 10/20 mg vs. Atorvastatin 20 mg on Apolipoprotein B/Apolipoprotein A1 in Korean Patients with Type 2 Diabetes Mellitus: Results of a Randomized Controlled Trial
Background Although the efficacy of ezetimibe/simvastatin and atorvastatin on traditional lipid parameters has been studied extensively , the apolipoprotein B/apolipoprotein A1 ( ApoB/ApoA1 ) ratio , which has a better predictive value for cardiovascular events , has not previously been used as a primary endpoint in these two treatment groups . Objective Our objective was to compare the efficacy and safety of ezetimibe/simvastatin 10/20 mg versus atorvastatin 20 mg once daily in Korean patients with type 2 diabetes mellitus . Study Design This study was an open-label , r and omized , controlled study . Type 2 diabetes patients with high levels of low-density lipoprotein ( LDL ) cholesterol ( > 100 mg/dL ) were r and omized to receive ezetimibe/simvastatin or atorvastatin . Main Outcome MeasureThe primary endpoint was the difference in the percent change of ApoB/ApoA1 at 12 weeks , and secondary endpoints were changes in lipid profiles , glycosylated hemoglobin ( HbA1c ) , homeostatic model assessment ( HOMA ) index , and C-reactive protein . Results In total , 132 patients ( 66 for each group ) were enrolled and r and omized . After 12 weeks of treatment , the ApoB/ApoA1 ratio was significantly reduced in both groups ; however , the difference of changes between the two groups was not statistically significant ( ezetimibe/simvastatin −38.6 ± 18.0 % vs. atorvastatin −34.4 ± 15.5 % ; p = 0.059 ) . There were no significant differences in changes to total cholesterol , LDL cholesterol , high-density lipoprotein cholesterol , triglycerides , ApoB , and ApoB48 between the two groups . However , the increments of ApoA1 were significantly greater in the ezetimibe/simvastatin group than in the atorvastatin group ( 2.8 ± 10.0 vs. −1.8 ± 9.8 % ; p = 0.002 ) . In the per- protocol analysis , improvement in ApoB/ApoA1 was significantly greater in the ezetimibe/simvastatin group ( −42.8 ± 11.8 vs. −36.7 ± 13.2 % ; p = 0.019 ) . The changes in HbA1c , HOMA index , and C-reactive protein were comparable between the two groups . The adverse reaction rate was similar between the two groups ( 24.2 vs. 34.9 % ; p = 0.180 ) . Conclusion Ezetimibe/simvastatin 10/20 mg is comparable to atorvastatin 20 mg for the management of dyslipidemia , and may have more favorable effects on apolipoprotein profiles than atorvastatin 20 mg in Korean patients with type 2 diabetes mellitus
Population Characteristics and Study Quality of Included Trials , by Combination Therapy Agent and Potency Comparison Long-Term Clinical Outcomes We found insufficient evidence to compare long-term clinical outcomes ( mortality , acute coronary events , cerebrovascular events , and revascularization procedures ) for all combination therapy and statin intensity comparisons .
Figure 1 presents an evidence map of studies that evaluated these
Atherosclerotic cardiovascular disease ( ASCVD ) affects more than 15 million Americans ( 1 ) and is the leading cause of death for both men and women in the United States ( 2 ) .
Trials have demonstrated reductions in low-density lipoprotein ( LDL ) cholesterol levels ( 3 ) and decreased ASCVD risk with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor ( statin ) monotherapy ( 4 ) .
Over the past decade , statins have often been used in combination with other lipid-modifying agents .
Recently , several high-profile r and omized , controlled trials ( RCTs ) have evaluated add-on therapy ( 57 ) , wherein statin monotherapy is compared with the combination of the same statin dose and another lipid-modifying agent .
Add-on combination therapy can lead to superior lipid outcomes , but studies have not shown decreased rates of cardiovascular death , myocardial infa rct ion , revascularization , or stroke ( 57 ) .
Therefore , the 2013 American College of Cardiology ( ACC ) and American Heart Association ( AHA ) guidelines recommend moderate- or high-intensity statin monotherapy as the first-line strategy for ASCVD risk reduction among patients with LDL cholesterol levels of 4.91 mmol/L or greater ( 190 mg/dL ) , preexisting ASCVD , diabetes mellitus ( DM ) , or estimated 10-year ASCVD risk of 7.5 % or greater ( 8) .
Adverse effects are more common with higher-intensity statin regimens ( 9 ) , and musculoskeletal adverse events occur frequently among patients with the C variant in the SLCO1B1 gene ( 10 ) .
The 2013 ACC/AHA guidelines suggest that clinicians consider moderated combination therapy with a lower-intensity statin and another lipid-modifying medication among high-risk patients ( LDL cholesterol level 4.91 mmol/L [ 190 mg/dL ] , preexisting ASCVD , or DM ) who are intolerant of or unresponsive to statins ( evidence grade E : expert opinion ) ( 8) .
Yet , it is unclear whether this strategy results in similar ASCVD risk reductions and fewer adverse effects compared with higher-intensity statin monotherapy .
A 2009 systematic review that examined these questions found insufficient evidence to weigh benefits and risks of moderated combination therapy ( 12 ) .
We aim ed to compare the effectiveness , safety , and tolerability of moderated combination therapy of statin with another lipid-modifying medication ( bile acid sequestrant , ezetimibe , fibrate , niacin , or -3 fatty acid ) with those of higher-intensity statin monotherapy among high-risk patients .
We sought to compare the long-term clinical benefits and short-term lipid effects of moderated combination therapy with those of higher-intensity statin monotherapy , as well as to determine whether these regimens differ in rates of adherence and harms .
Given the recent release of the 2013 ACC/AHA guidelines ( 8) , we narrowed the scope of this manuscript to focus on evidence most relevant to high-risk population s for whom combination therapy might be considered .
Prior studies have suggested schemes to group statins on the basis of their reported LDL cholesterol reduction ( 17 , 18 ) , which are similar to the strategy used by the ACC/AHA committee ( 8) .