Simvastatin Increases HDL-C and Apolipoprotein A-1 Levels Significantly More Than Atorvastatin - PowerPoint PPT Presentation

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Simvastatin Increases HDL-C and Apolipoprotein A-1 Levels Significantly More Than Atorvastatin

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Simvastatin Increases HDL-C and Apolipoprotein A-1 Levels Significantly More Than Atorvastatin

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    1. Simvastatin Increases HDL-C and Apolipoprotein A-1 Levels Significantly More Than Atorvastatin John P. Kastelein, Evan A. Stein, Michael A. Davidson, John R. Crouse, Leiv Ose, Minzhi Liu, Michael R. Melino, Laura OGrady, Michel Mercuri, Yale B. Mitchel For the Simvastatin Atorvastatin HDL Study Group; Academic Medical Center, Amsterdam, The Netherlands Merck Research Laboratories, Rahway, New Jersey, USA

    2. Simvastatin/Atorvastatin HDL Study Background HDL-C and apolipoprotein (apo) A-1 levels are inversely related to the risk of coronary heart disease. Recently the VA-HIT study suggested that modest increases in HDL-C could have significant benefits on cardiovascular events. Statins, in addition to lowering LDL-C and TG, increase HDL-C levels. However, recent data suggest that a differential effect of simvastatin and atorvastatin on HDL-C exists, in that at higher doses of both drugs simvastatin raises HDL-C more than atorvastatin.

    3. Simvastatin/Atorvastatin HDL Study Methods This multicenter, double-blind, 36-week dose titration study was designed to evaluate the effects of simvastatin and atorvastatin on HDL-C and apo A-1 levels. Following a 4-week diet run-in period, 826 patients (47% female) with LDL-C > 160 mg/dL and TG < 350 mg/dL were randomized to simvastatin or atorvastatin for 36 weeks.

    4. Simvastatin/Atorvastatin HDL Study Design Treatment Simvastatin 40 mg/day period 1 (6 weeks), and 80 mg/day periods 2 (6 weeks) and 3 (24 weeks) Atorvastatin 20 mg/day period 1 (6 weeks), 40 mg/day period 2 (6 weeks) and 80 mg/day period 3 (24 weeks) Primary lipid endpoint for week 6, 12 and 18/36 efficacy analysis HDL cholesterol Key secondary lipid endpoint for week 6, 12 and 18/36 efficacy analysis Apolipoprotein A-1

    5. Study Design Diet run-in

    6. Simvastatin/Atorvastatin HDL Study Demographic Characteristics

    7. Simvastatin/Atorvastatin HDL Study Baseline Lipid Levels

    8. Simvastatin/Atorvastatin HDL Study Changes in HDL-C and Apo A-1 at Week 6/12

    9. Simvastatin/Atorvastatin HDL Study Change in HDL-C for Each Treatment Period

    11. Larger Increases in HDL-C with Simvastatin Were Seen in Patients with Both Low and High HDL-C Levels

    14. Number of Patients with Clinically Relevant Elevations in ALT and CK During the Third Treatment Period

    15. Simvastatin/Atorvastatin HDL Study ~ Summary At clinically equipotent doses for lowering LDL-C, simvastatin increased HDL-C and apo A-1 more than atorvastatin: Differences between the drugs in increasing HDL-C were larger at higher doses. 80 mg simvastatin increased HDL-C by 7.6% (compared to 3.1% with atorvastatin 80 mg) and raised apo A-1 2.5% (compared to a 3.5% decrease with atorvastatin). These data on HDL and apo A-1 confirm previously reported results of another large comparative multicenter trial. Both drugs produced comparable and substantial reductions in LDL-C. Differences between atorvastatin and simvastatin were statistically significant but small in comparison to the magnitude of LDL-C reduction. Both drugs produced substantial reductions in TGs, with atorvastatin showing slightly larger reductions than simvastatin. At the 80 mg dose more patients treated with atorvastatin were discontinued due to clinically significant increases in ALT (3.8% of total participants or 5.9% of women) compared to simvastatin (0.5% and 0.6%, respectively).

    16. Simvastatin/Atorvastatin HDL Study ~ Conclusions Simvastatin increased HDL-C and apo A-1 consistently more than atorvastatin Both agents were well tolerated at doses that led to approximately 50% reductions in LDL-C (atorvastatin 40 mg and simvastatin 80 mg). LDL-C reduction achieved with 80 mg atorvastatin during the final 24 week period was 2.3% greater than that achieved with 40 mg atorvastatin. However, at the highest dose of atorvastatin (80 mg), the benefit of the small additional percent LDL-C reduction may be offset by: higher risk of clinically significant and consecutive increases in ALT necessitating withdrawal from study reduction in apo A-1 modest effect on HDL-C Benefits need to be weighed against the risk for the increased incidence of liver adverse effects with 80 mg atorvastatin