January 1, 2007 • www.internalmedicinenews.com Cardiovascular Medicine 31 Fluvastatin XL Cuts LDL Level With Less Myalgia Trial finds drug is well tolerated and less likely than Results of Fluvastatin With and Without other statins to cause muscle-related side effects. Ezetimibe at 12 Weeks Fluvastatin + BY BRUCE JANCIN in the trial had already discontinued an- Ezetimibe Fluvastatin Ezetimibe Denver Bureau other statin for that very reason. Patients having muscle-related side effects 24.2% 17.4% 14.1% Dr. Stein stressed he was not talking Patients dropping out of study because C HICAGO — Fluvastatin XL, either about myopathy and rhabdomyolysis, se- of muscle-related side effects 7.6% 4.3% 3.1% alone or in combination with ezetimibe, is rious but rare side effects of statin thera- an effective, well-tolerated, and safe option py. He focused on mild to moderate mus- Patients reaching LDL-cholesterol level <100 mg/dL 1.5% 33.3% 67.2% for lowering LDL cholesterol in patients cle pain, cramping, and weakness. The big who can’t tolerate other statins because of randomized trials suggest the prevalence Patients reaching NCEP LDL-cholesterol goal 10.6% 43.5% 73.4% muscle-related side effects, Dr. Evan A. of such problems is 2%-4%, but many clin- EWS

Stein said at the annual scientific sessions icians say the figure in everyday practice N Reduction in: of the American Heart Association. is much higher, he said. Level of LDL cholesterol (mean) 15.6% 32.8% 46.1%

Statin-associated mild to moderate mus- In the trial at 27 U.S. and European cen- EDICAL Level of C-reactive protein (median) 0% 7.9% 18.6% M cle-related side effects such as myalgias, ters, 199 patients with a history of intoler-

cramping, and weakness are far more ance to statins other than fluvastatin due to Note: Based on a study of 199 patients who had discontinued other statins LOBAL common and debilitating in daily practice muscle-related side effects were random- because of muscle-related side effects. G than suggested by ized to 12 weeks of Source: Dr. Stein LSEVIER high-profile, highly The data showed ezetimibe plus E selective clinical tri- 85% of subjects placebo, fluvastatin als. And fluvastatin were maintained XL plus placebo, or cent of subjects were high risk by Nation- curred in 10.5% of patients. Thirty-eight XL is less likely on fluvastatin XL both drugs. al Cholesterol Education Program (NCEP) percent of patients with muscle-related than other statins at 80 mg/day LDL cholesterol criteria. Fluvastatin XL enabled many to side effects said muscular pain prevented to cause these prob- without muscle- lowering with flu- reach their NCEP LDL cholesterol goal, even moderate exertion during everyday lems, said Dr. Stein, related problems. vastatin, with or which otherwise would not have been pos- activities, Dr. Stein said. director of the without ezetimibe, sible because of their muscle problems on PRIMO, sponsored by Novartis Phar- Metabolic and Ath- DR. STEIN was greater than other statins. An estimated 1-2 million pa- maceuticals, showed the rate of muscle erosclerosis Re- with ezetimibe tients have ended statin therapy due to symptoms was 10.9% with pravastatin at 40 search Center, Cincinnati. alone. Muscle-related side effects in the two such side effects, the physician said. mg/day, 14.9% with atorvastatin at 40-80 He presented a randomized double-blind fluvastatin arms were slightly lower than The impression that prevalence of mild mg/day, and 18.2% with simvastatin at 40- placebo-controlled trial restricted to pa- with ezetimibe. And when such side effects to moderate muscle-related side effects to 80 mg/day. Fluvastatin XL at 80 mg/day tients forced to discontinue statins other occurred in patients on fluvastatin alone, statins is much higher in practice than in was associated with a 5.1% rate (Cardio- than fluvastatin (Lescol) because of muscle- they began in the first month, whereas clinical trials was recently borne out in an vasc. Drugs Ther. 2005;19:403-14). related side effects. The results showed with ezetimibe they started any time dur- observational study involving an unse- Audience members argued that Dr. 85% of participants could be maintained on ing the 3-month trial. The combination lected population of 7,924 French patients Stein’s trial should have featured an arm in- fluvastatin XL at 80 mg/day or fluvastatin therapy’s effect upon C-reactive protein on high-dose statin therapy. volving rechallenge to an offending statin, XL 80 mg plus ezetimibe (Zetia) at 10 lowering is difficult to explain but has con- The study—the Prediction of Muscular though Dr. Stein said most patients found mg/day without muscle-related problems. sistently been seen in other studies of eze- Risk in Observational conditions (PRI- their muscle symptoms sufficiently un- Moreover, the dropout rate owing to timibe plus various statins, Dr. Stein said. MO)—was the first to look at statin-relat- pleasant that they would balk at reexpo- muscle-related side effects in the 12-week Mean baseline LDL cholesterol in the ed muscle side effects in clinical practice. sure. Dr. Stein is a consultant to Novartis, study was less than 5%, although everyone study cohort was 175 mg/dL. Eighty per- It found that muscular symptoms oc- which funded the trial. ■ Medication Combo Trumps Rosuvastatin in Cutting LDL

BY MIRIAM E. TUCKER tients with type 2 diabetes, mg/dL (3.4 mmol/L) for the Senior Writer 840 with metabolic syn- Greater Reductions in LDL-Cholesterol Level With E/S nondiabetics with metabolic syn- drome but without diabetes, In Type 2 Diabetes and Metabolic Syndrome Patients drome, or 160 mg/dL (4.1 C OPENHAGEN — A combina- 1,722 with neither condition, mmol/L) for the group with nei- tion of ezetimibe and simvastatin and 22 who could not be ther. A total of 88.2% of the E/S Ezetimibe/Simvastatin group Rosuvastatin group provides additional lipid-modify- placed in a category because patients versus 81.9% of the R pa- ing benefits compared with rosu- of missing data were ran- 10/20 mg 10/40 mg 10/80 mg 10 mg 20 mg 40 mg tients achieved an LDL-choles- vastatin monotherapy among pa- domized to one of six treat- terol level of less than 100 mg/dL tients with type 2 diabetes or with ment groups: ezetimibe/sim- (2.6 mmol/L), whereas 45.3% vs. metabolic syndrome without di- vastatin (E/S) in doses of 10 29.5% reached an LDL-choles- abetes, Dr. Alberico L. Catapano mg/20 mg (respectively), 10 terol level of less than 70 mg/dL reported at the annual meeting of mg/40 mg, or 10 mg/80 mg; (1.8 mmol/L). All of these differ- EWS

the European Association for the or rosuvastatin (R) in doses of N ences were significant, he said. Study of Diabetes. 10, 20, or 40 mg. All had hy- Reductions in total cholesterol, 45.8% “Overall, ezetimibe/simvas- percholesterolemia, defined EDICAL non-HDL cholesterol, apolipo- 51.5% 52.3% M tatin, a single-tablet, dual-choles- as an LDL-cholesterol level of 54.8% 56.7% protein B, and triglycerides were 61% terol inhibitor, offers an effective 145-249 mg/dL (3.7-6.4 LOBAL also significantly greater with G and well-tolerated lipid-modify- mmol/L) with triglycerides Note: Based on a study of 2,959 patients. E/S; there were no significant dif- ing option for the treatment of at or below 350 mg/dL (4 Source: Dr. Catapano ferences between the two treat- LSEVIER hypercholesterolemia in patients mmol/L). E ments in HDL cholesterol, or with type 2 diabetes and meta- Among the whole cohort high-sensitivity C-reactive protein. bolic syndrome,” said Dr. Cata- of 2,959 patients, significant re- tween E/S and R was significant and those with neither (55.6% Both drugs showed similar pano, of the department of phar- ductions in LDL cholesterol from for the whole cohort (55.8% vs. vs. 51%), Dr. Catapano reported. rates of adverse events (8.1% E/S macological sciences at the baseline were seen among the 51.6%). Consistent with that, Overall, 95.3% of the E/S vs. 7.4% R) and discontinuations University of Milan. E/S group at the usual starting, LDL-cholesterol lowering was group, compared with 92.1% of because of adverse events (2.2% In a post-hoc analysis of data next highest, and maximum dos- also greater with E/S in the type the R group, attained the recom- for both drugs). Proteinuria was from a multicenter, double-blind, ing levels. (See chart.) 2 diabetes patients (58.5% vs. mended LDL-cholesterol goals of higher at baseline in the R group randomized, 6-week study spon- Across all doses, the difference 54.2%), nondiabetics with meta- less than 100 mg/dL (2.6 and among those with diabetes, sored by Merck & Co., 375 pa- in LDL-cholesterol reduction be- bolic syndrome (55% vs. 51.8%), mmol/L) for the diabetics, 130 he noted. ■