Advertisement

Safety and Efficacy of Ezetimibe Added on to Rosuvastatin 5 or 10 mg Versus Up-Titration of Rosuvastatin in Patients With Hypercholesterolemia (the ACTE Study)

      The present multicenter, 6-week, randomized, double-blind, parallel-group, clinical trial evaluated the safety and efficacy of ezetimibe (10 mg) added to stable rosuvastatin therapy versus up-titration of rosuvastatin from 5 to 10 mg or from 10 to 20 mg. The study population included 440 subjects at moderately high/high risk of coronary heart disease with low-density lipoprotein (LDL) cholesterol levels higher than the National Cholesterol Education Program Adult Treatment Panel III recommendations (<100 mg/dl for moderately high/high-risk subjects without atherosclerotic vascular disease or <70 mg/dl for high-risk subjects with atherosclerotic vascular disease). Pooled data demonstrated that ezetimibe added to stable rosuvastatin 5 mg or 10 mg reduced LDL cholesterol by 21%. In contrast, doubling rosuvastatin to 10 mg or 20 mg reduced LDL cholesterol by 5.7% (between-group difference of 15.2%, p <0.001). Individually, ezetimibe plus rosuvastatin 5 mg reduced LDL cholesterol more than did rosuvastatin 10 mg (12.3% difference, p <0.001), and ezetimibe plus rosuvastatin 10 mg reduced LDL cholesterol more than did rosuvastatin 20 mg (17.5% difference, p <0.001). Compared to rosuvastatin up-titration, ezetimibe add-on achieved significantly greater attainment of LDL cholesterol levels of <70 or <100 mg/dl (59.4% vs 30.9%, p <0.001), and <70 mg/dl in all subjects (43.8% vs 17.5%, p <0.001); produced significantly greater reductions in total cholesterol, non–high-density lipoprotein cholesterol, and apolipoprotein B (p <0.001); and resulted in similar effects on other lipid parameters. Adverse experiences were generally comparable among the groups. In conclusion, compared to up-titration doubling of the rosuvastatin dose, ezetimibe 10 mg added to stable rosuvastatin 5 mg or 10 mg produced greater improvements in many lipid parameters and achieved greater attainment of the National Cholesterol Education Program Adult Treatment Panel III recommended LDL cholesterol targets in subjects with elevated LDL cholesterol and at moderately high/high coronary heart disease risk.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Grundy S.M.
        • Cleeman J.I.
        • Merz C.N.
        • Brewer Jr, H.B.
        • Clark L.T.
        • Hunninghake D.B.
        • Pasternak R.C.
        • Smith Jr, S.C.
        • Stone N.J.
        Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines.
        J Am Coll Cardiol. 2004; 44: 720-732
        • Smith Jr, S.C.
        • Allen J.
        • Blair S.N.
        • Bonow R.O.
        • Brass L.M.
        • Fonarow G.C.
        • Grundy S.M.
        • Hiratzka L.
        • Jones D.
        • Krumholz H.M.
        • Mosca L.
        • Pearson T.
        • Pfeffer M.A.
        • Taubert K.A.
        AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease; 2006 update endorsed by the National Heart, Lung, Blood Institute.
        J Am Coll Cardiol. 2006; 47: 2130-2139
        • Liang K.Y.
        • Zeger S.L.
        Longitudinal data analysis of continuous and discrete responses for pre-post designs.
        Sankya Ser B. 2000; 62: 134-148
        • Miettinen O.
        • Nurminen M.
        Comparative analysis of two rates.
        Stat Med. 1985; 4: 213-226
        • Gagne C.
        • Bays H.E.
        • Weiss S.R.
        • Mata P.
        • Quinto K.
        • Melino M.
        • Cho M.
        • Musliner T.A.
        • Gumbiner B.
        Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia.
        Am J Cardiol. 2002; 90: 1084-1091
        • Pearson T.A.
        • Denke M.A.
        • McBride P.E.
        • Battisti W.P.
        • Brady W.E.
        • Palmisano J.
        A community-based, randomized trial of ezetimibe added to statin therapy to attain NCEP ATP III goals for LDL cholesterol in hypercholesterolemic patients: the ezetimibe add-on to statin for effectiveness (EASE) trial.
        Mayo Clin Proc. 2005; 80: 587-595
        • Conard S.E.
        • Bays H.E.
        • Leiter L.A.
        • Bird S.R.
        • Rubino J.
        • Lowe R.S.
        • Tomassini J.E.
        • Tershakovec A.M.
        Efficacy and safety of ezetimibe added on to atorvastatin (20 mg) versus uptitration of atorvastatin (to 40 mg) in hypercholesterolemic patients at moderately high risk for coronary heart disease.
        Am J Cardiol. 2008; 102: 1489-1494
        • Leiter L.A.
        • Bays H.
        • Conard S.
        • Bird S.
        • Rubino J.
        • Hanson M.E.
        • Tomassini J.E.
        • Tershakovec A.M.
        Efficacy and safety of ezetimibe added on to atorvastatin (40 mg) compared with uptitration of atorvastatin (to 80 mg) in hypercholesterolemic patients at high risk of coronary heart disease.
        Am J Cardiol. 2008; 102: 1495-1501
        • Farnier M.
        • Volpe M.
        • Massaad R.
        • Davies M.J.
        • Allen C.
        Effect of co-administering ezetimibe with on-going simvastatin treatment on LDL-C goal attainment in hypercholesterolemic patients with coronary heart disease.
        Int J Cardiol. 2005; 102: 327-332
        • Jones P.H.
        • Davidson M.H.
        • Stein E.A.
        • Bays H.E.
        • McKenney J.M.
        • Miller E.
        • Cain V.A.
        • Blasetto J.W.
        Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial).
        Am J Cardiol. 2003; 92: 152-160