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) .
Efficacy of combination of Ezetimibe 10 mg and rosuvastatin 2.5 mg versus rosuvastatin 5 mg monotherapy for hypercholesterolemia in patients with type 2 diabetes
Background Statins are used to treat hypercholesterolemia in patients with type 2 diabetes mellitus , but many of these patients fail to achieve the target LDL-C level . Recent reports have suggested that a synergistic effect can be obtained by concomitant administration of the cholesterol absorption inhibitor ezetimibe and a statin . However , in patients with type 2 diabetes who are already being treated with satins , it remains unclear whether it is more effective to add ezetimibe or to increase the statin dose . Therefore , this study was performed to examine the effects of these two regimens on LDL-C and lipoproteins . Methods The subjects were type 2 diabetic patients under treatment with rosuvastatin ( 2.5 mg daily ) , who had LDL-C levels ≥80 mg/dL. They were r and omly allocated to a group that received add-on therapy with ezetimibe at 10 mg/day ( combination group , n = 40 ) or an increase of the rosuvastatin dose to 5 mg/day ( dose escalation group , n = 39 ) . These two groups were compared at baseline and after 12 weeks of treatment . Results The percent change of LDL-C was −31 % in the combination group and −12 % in the dose escalation group . Both groups showed a significant decrease , but the decrease was greater in the combination group . In both groups , there was a significant decrease in the levels of small dense LDL-C , oxidized LDL and remnant-like lipoprotein cholesterol . For all of these parameters , the percent changes were greater in the combination group . Only the combination group showed a significant decrease of triglycerides . Multivariate analysis was performed to identify factors associated with reaching an LDL-C level < 80 mg/dL. As a result , add-on therapy with ezetimibe was extracted as a factor related to improvement of LDL-C. Conclusions Compared with increasing the dose of rosuvastatin , the combination of rosuvastatin and ezetimibe not only achieves quantitative but also qualitative improvement of serum lipid levels in type 2 diabetic patients , suggesting that this combination could suppress the progression of atherosclerosis . Trial registration
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) .