3028 Cat: Valvular heart disease/Heart valve surgery - adult
LIPID LOWERING IN PATIENTS WITH MILD AORTIC STENOSIS AND ELEVATED LOW DENSITY LIPOPROTEIN: THE SEAS STUDY
A.M. Greve1, C.N. Bang1, C. Gohlke-Baerwolf2, K. Boman3, K. Egstrup4,
Y.A. Kesäniemi5, S. Ray6, T.R. Pedersen7, N.M. Rajamannan8,9, K. Wachtell1,10
1. Department of Cardiology, Glostrup University Hospital, Copenhagen, Denmark
2. Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany
3. Department of Medicine, Institution of Public Health and Clinical Medicine, Umeå University, Skelleftå, Sweden
4. Medicinsk Afdeling, OUH Svendborg Sygehus, Denmark
5. Institute of Clinical Medicine, Department of Medicine, University of Oulu and Clinical Research center, Oulu University Hospital, Oulu, Finland
6. University Hospitals of South Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom
7. Center for Preventive medicine, Oslo University Hospital, Ullevål and University of Oslo, Oslo, Norway
8. Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester MN; USA
9. Most Sacred Heart of Jesus Cardiology and Valvular Institute, Sheboygan, WI, USA
10. Department of Cardiology, Örebro University Hospital, Örebro, Sweden
Aims: To examine if pretreatment low density lipoprotein cholesterol (LDL) levels and aortic stenosis (AS) severity alter the efficacy of lipid-lowering therapy in AS patients.
Methods and Results: Asymptomatic patients with AS randomized (1:1) to 40 mg Simvastatin + 10 mg Ezetimibe combination vs. placebo and ≥2 echocardiograms in the SEAS trial. The main endpoint in this substudy was impact of randomization on the association between pretreatment LDL levels and progression in AS severity, as determined by peak aortic jet velocity and a composite cardiovascular endpoint. Treatment effect was analyzed by separating patients into quartiles of LDL levels in mild and moderate-to-severe AS (>3.0 m/sec). A total of 1,682 patients were followed for a mean of 4.4 years (7,373 patient-years of follow-up). Among patients in the highest quartile of LDL with mild AS at baseline (p=0.03 for interaction), Simvastatin-Ezetimibe was associated with lesser end of study progression in peak jet velocity (OR 0.85, 95% CI: 0.74 – 0.98, p=0.03). In a parallel analysis, Simvastatin-Ezetimibe also reduced composite endpoints in the highest quartile of LDL with mild AS at baseline (HR 0.46, 95% CI: 0.23 – 0.90, p=0.02). Conversely, there was no detectable effect of Simvastatin-Ezetimibe combination on AS progression in the other LDL quartiles with mild AS baseline (p=0.75). No effect of lipid lowering was noted in patients with moderate to severe aortic stenosis irrespective of pretreatment LDL levels (p=0.87).
Conclusion: In a non-prespecified post-hoc analysis, asymptomatic patients with mild AS and elevated LDL benefited from lipid-lowering therapy (SEAS study: NCT00092677).