Comparative effects on lipid levels of combination therapy with a statin and extended-release niacin or ezetimibe versus a statin alone (the COMPELL study).
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 randomized 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.
McKenney
James M
JM
National Clinical Research, Richmond, VA 23227, United States. jmckenney@ncrinc.net <jmckenney@ncrinc.net>
Jones
Peter H
PH
Bays
Harold E
HE
Knopp
Robert H
RH
Kashyap
Moti L
ML
Ruoff
Gary E
GE
McGovern
Mark E
ME
D000328:Adult; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000097:blood; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage*; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D009525:Niacin / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage*; D000068718:Rosuvastatin Calcium; D019821:Simvastatin / Q000008:administration & dosage*; D013449:Sulfonamides / Q000008:administration & dosage*; D016896:Treatment Outcome
D008078:Cholesterol, LDL; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D005464:Fluorobenzenes; D006538:Heptanoic Acids; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D009525:Niacin; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin; D019821:Simvastatin