S L I D E 0 Effect of statin therapy on the natural history of thoracic aortic aneurysms. Louis H. Stein, Jessica Berger, Maryann Tranquilli, John A. Elefteriades.

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S L I D E 0 Effect of statin therapy on the natural history of thoracic aortic aneurysms. Louis H. Stein, Jessica Berger, Maryann Tranquilli, John A. Elefteriades. The Aortic Institute at Yale – New Haven Hospital

S L I D E 1 Bench top to bedside interaction Medial Degeneration ROS MMP -2 MMP -9 NADH / NADPH (VSM) Statin Beta blockers ARB

S L I D E 2 Statin therapy and the Aorta Statins inhibit the progression of atherosclerosis. In AAA, conflicting data on rate of aneurysm expansion. 1,2,3 No specific data on TAA exists at present. Does statin therapy impact the clinical course of Thoracic aortic aneurysms? 1.Karrowni W, et al “Statin therapy reduces growth of abdominal aortic aneurysms.”J Investig Med Dec;59(8): Mosorin M, et al. “The use of statins and fate of small abdominal aortic aneurysms.” Interact Cardiovasc Thorac Surg Aug;7(4): Schlösser FJ, et al. “Growth predictors and prognosis of small abdominal aortic aneurysms.”J Vasc Surg Jun;47(6): Epub 2008 Apr 28.

S L I D E 3 Baseline Characteristics CharacteristicNo StatinStatinp - value n1191 (76%)369 (24%) Aneurysm Site Root158 (13%)46 (12%)NS Arch121 (10%)40 (11%)NS Ascending595 (50%)192 (52%)NS Descending196 (16%)66 (18%)NS TAA121 (10%)25 (7%)NS Medications ACE277 (23%)103 (28%)NS Antiarrhythmia26 (2%)20 (5%)P=0.004 ARB78 (7%)65 (17%)p<0.001 Beta-blocker520 (43%)224 (61%)p<0.001 CCB252 (21%)101 (27%)p = Insulin12 (1%)10 (3%)NS NSAID38 (3%)6 (2%)NS

S L I D E 4 Baseline Characteristics CharacteristicNo StatinStatinp - value HTNp < None332 (30%)48 (14%) Mild419 (39%)133 (49%) Moderate218 (20%)111(33%) Severe116 (11%)44 (13%) CAD216 (18%)123 (33%)p< CHF74 (6%)19 (5%)NS AAA168 (12%)42 (10%)NS PVD66 (5%)22 (6%)NS Renalp < None960 (91%)279 (87.7%) Mild72 (6.8%)19 (6.0%) Moderate14 (1.3%)1 (0.1%) Severe9 (0.8%)7 (2%) CharacteristicNo StatinStatinp - value COPDNS None818 (77%)224 (69%) Mild136 (13%)57 (18%) Moderate78 (7%)33 (10%) Severe36 (3%)11 (4%) Obesity43 (3%)1 (0.25%)p < Marfans57 (5%)2 (0.5%)p =

S L I D E 5 * * * * * * * * * - p <0.05 Percent of patients with and without statin therapy experiencing dissection or rupture by aneurysm location Percent of patients with and without statin therapy requiring surgical intervention by aneurysm location Percent of patients

S L I D E 6 Kaplan-Meier freedom from aneurysm or rupture for ascending, arch, and descending aorta. prob chi-squared =

S L I D E 7 Kaplan-Meier freedom from surgery for ascending, arch, and descending aorta. prob chi-squared < Time (months)

S L I D E 8 Does ARB therapy impact the protection provided by statins? n No StatinStatin No ARB ARB7156 Laboratory data demonstrates a protective effect provided by ARBs in in vivo models. 1 Clinical data has also demonstrated ARB slow the progression of thoracic aortic aneurysms in patients with Marfan’s Disease. 2 Our data show an increased prevalence of ARB treatment among those treated with Statins. 1.Habashi TM, et al. Angiotensin II type 2 receptor signaling attenuates aortic aneurysm in mice through ERK antagonism. Science Apr 15;332(6027): Brooke BS, et al. Angiotensin II blockade and aortic-root dilation in Marfan's syndrome. N Engl J Med Jun 26;358(26):

S L I D E 9 Percent of patients with and without ARB therapy experiencing dissection or rupture by aneurysm location Percent of patients with and without ARB therapy requiring surgical intervention by aneurysm location Percent of patients

S L I D E 10 Single logistic regression Multiple Logistic Regression Regression analysis of the effect of statin and ARB therapy on thoracic aortic aneurysm outcome

S L I D E 11 Conclusions Statin therapy has a protective effect against TAAA progressing to dissection, rupture, or surgery. This protective effect is seen in aneurysms of the ascending, arch, descending, and thoracoabdominal aorta. The protective effect is not demonstrated in aneurysms of the aortic root. These findings are in line with the current understanding of the physiology of the aorta – given the different embryologic derivation of different segments of the aorta. The effect on rupture or dissection is independent of ARB therapy. ARB therapy seem to help protect against requiring surgery. Effect of stain therapy on growth rate is currently under review.