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) .
Comparison of anti-inflammatory effects and high-density lipoprotein cholesterol levels between therapy with quadruple-dose rosuvastatin and rosuvastatin combined with ezetimibe
Background Statins are frequently administered to reduce low-density lipoprotein cholesterol ( LDL-C ) and vascular inflammation , because LDL-C and high sensitive C-reactive protein ( hs-CRP ) are associated with high risk for cardiovascular events . When statins do not reduce LDL-C to desired levels in high-risk patients with coronary artery disease ( CAD ) , ezetimibe can be added or the statin dose can be increased . However , which strategy is more effective for treating patients with CAD has not been established . The present study compares anti-inflammatory effects and lipid profiles in patients with CAD and similar LDL-C levels who were treated by increasing the statin dose or by adding ezetimibe to the original rosuvastatin dose to determine the optimal treatment for such patients . Methods 46 patients with high-risk CAD and LDL-C and hs-CRP levels of > 70 mg/dL and > 1.0 mg/L , respectively , that were not improved by 4 weeks of rosuvastatin ( 2.5 mg/day ) were r and omly assigned to receive 10 mg ( R10 , n = 24 ) of rosuvastatin or 2.5 mg/day of rosuvastatin combined with 10 mg/day of ezetimibe ( R2.5/E10 , n = 22 ) for 12 weeks . The primary endpoint was a change in hs-CRP . Results Baseline characteristics did not significantly differ between the groups . At 12 weeks , LDL-C and inflammatory markers ( hs-CRP , interleukin-6 , tumour necrosis factor-alpha and pentraxin 3 ) also did not significantly differ between the two groups ( LDL-C : R10 vs. R2.5/E10 : -19.4 ± 14.2 vs. -22.4 ± 14.3 mg/dL ) . However , high-density lipoprotein cholesterol ( HDL-C ) was significantly improved in the R10 , compared with R2.5/E10 group ( 4.6 ± 5.9 vs. 0.0 ± 6.7 mg/dL ; p < 0.05 ) . Conclusion Both enhanced therapies exerted similar anti-inflammatory effects under an equal LDL-C reduction in patients with high-risk CAD despite 2.5 mg/day of rosuvastatin . However , R10 elevated HDL-C more effectively than R2.5/E10.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) .