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
SLIDE 0
Bench top to bedside interaction
NADH / NADPH
(VSM)
ROS
MMP -2
MMP -9
Medial Degeneration
ARB
Statin
Beta blockers
SLIDE 1
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.
2.
3.
Karrowni W, et al “Statin therapy reduces growth of abdominal aortic aneurysms.”J Investig
Med. 2011 Dec;59(8):1239-43.
Mosorin M, et al. “The use of statins and fate of small abdominal aortic aneurysms.” Interact
Cardiovasc Thorac Surg. 2008 Aug;7(4):578-81.
Schlösser FJ, et al. “Growth predictors and prognosis of small abdominal aortic aneurysms.”J
Vasc Surg. 2008 Jun;47(6):1127-33. Epub 2008 Apr 28.
SLIDE 2
Baseline Characteristics
Characteristic
n
Aneurysm Site
Root
Arch
Ascending
Descending
TAA
Medications
No Statin
1191 (76%)
Statin
369 (24%)
p - value
158 (13%)
121 (10%)
595 (50%)
196 (16%)
121 (10%)
46 (12%)
40 (11%)
192 (52%)
66 (18%)
25 (7%)
NS
NS
NS
NS
NS
ACE
Antiarrhythmia
ARB
Beta-blocker
CCB
Insulin
NSAID
277 (23%)
26 (2%)
78 (7%)
520 (43%)
252 (21%)
12 (1%)
38 (3%)
103 (28%)
20 (5%)
65 (17%)
224 (61%)
101 (27%)
10 (3%)
6 (2%)
NS
P=0.004
p<0.001
p<0.001
p = 0.038
NS
NS
SLIDE 3
Baseline Characteristics
Characteristic
No Statin
Statin
HTN
p - value
p < 0.0001
None
Mild
Moderate
Severe
CAD
CHF
332 (30%)
419 (39%)
218 (20%)
116 (11%)
216 (18%)
74 (6%)
48 (14%)
133 (49%)
111(33%)
44 (13%)
123 (33%)
19 (5%)
AAA
PVD
Renal
None
Mild
Moderate
Severe
168 (12%)
66 (5%)
42 (10%)
22 (6%)
960 (91%)
72 (6.8%)
14 (1.3%)
9 (0.8%)
279 (87.7%)
19 (6.0%)
1 (0.1%)
7 (2%)
p< 0.0001
NS
Characteristic
COPD
No Statin
Statin
p - value
NS
None
818 (77%)
224 (69%)
Mild
136 (13%)
57 (18%)
Moderate
78 (7%)
33 (10%)
Severe
36 (3%)
11 (4%)
Obesity
43 (3%)
1 (0.25%)
p < 0.0039
Marfans
57 (5%)
2 (0.5%)
p = 0.0009
NS
NS
p < 0.0001
SLIDE 4
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
* - p <0.05
Percent of patients
SLIDE 5
Kaplan-Meier freedom from aneurysm or rupture
for ascending, arch, and descending aorta.
prob chi-squared = 0.0229
SLIDE 6
Kaplan-Meier freedom from surgery for
ascending, arch, and descending aorta.
Time (months)
prob chi-squared < 0.001
SLIDE 7
Does ARB therapy impact the protection provided by
statins?
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.
2.
n - 1357
No Statin
Statin
No ARB
962
267
ARB
71
56
Habashi TM, et al. Angiotensin II type 2 receptor signaling attenuates aortic aneurysm in mice through
ERK antagonism. Science. 2011 Apr 15;332(6027):361-5.
Brooke BS, et al. Angiotensin II blockade and aortic-root dilation in Marfan's syndrome. N Engl J Med.
2008 Jun 26;358(26):2787-95.
SLIDE 8
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
Thoracoabdominal
Thoracoabdominal
Descending
Descending
Arch
Arch
ARB
ARB
No ARB
Ascending
No ARB
Ascending
Root
Root
Any thoracic aorta
Any thoracic aorta
0
10
20
Percent of patients
30
0
20
40
60
Percent of patients
SLIDE 9
Regression analysis of the effect of statin and
ARB therapy on thoracic aortic aneurysm outcome
Single logistic regression
Multiple Logistic Regression
S L I D E 10
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.
S L I D E 11