Abstract 18126: Calcium Channel Blockers Accelerate Aortic Aneurysm and Cause Premature Lethality in Marfan Syndrome and Related Conditions
Calcium channel blockers (CCBs) are prescribed to patients with Marfan syndrome and related inherited thoracic aortic aneurysm (TAA) syndromes for prophylaxis against TAA progression, despite limited evidence for their efficacy in these disorders. Unexpectedly, Marfan mice treated with CCBs showed accelerated TAA expansion, rupture and premature lethality. In collaboration with other members of the GenTAC consortium, we conducted a case-control study to assess the effect of CCBs in humans with Marfan syndrome and related TAA conditions. These primarily included Loeys-Dietz, Turner and Ehlers-Danlos syndromes, familial thoracic aortic aneurysm, and bicuspid aortic valve with aneurysm. Marfan patients with native aortic roots at the time of enrollment who received CCBs (compared to other antihypertensive agents) had an increased risk of aortic dissection (odds ratio (OR) 12.5, p<0.05). Strong trends were maintained after correction for blood pressure (OR 12.7, p=0.06) or aortic root size (OR 11.2, p=0.08) at enrollment. A more profound effect of CCBs on outcome could be masked by the practice of intervening with aortic surgery when the aorta reaches a dimension that confers risk for dissection. In keeping with this hypothesis, we found that CCB-treated Marfan patients had an increased risk of aortic surgery (OR 5.5, p<0.001) when compared to patients on other antihypertensive agents, which remained significant when corrected for either blood pressure (OR 5.4, p<0.001) or aortic size (OR 5.0, p<0.01) at enrollment. For patients with other forms of TAA and native aortic roots at the time of enrollment (n=1,819), there was suggestion of an increased risk for aortic dissection in those who had taken CCBs, although this did not reach statistical significance (OR 4.7, p=0.26). This was most likely secondary to prophylactic surgical intervention, given that these patients again had an increased risk of aortic surgery (OR 2.4, p=0.004), which remained significant when corrected for either blood pressure (OR 2.2, p=0.016) or aortic size (OR 2.2, p=0.017) at enrollment. These data indicate that CCB treatment exacerbates aortic disease in Marfan syndrome and related TAA conditions, and suggests that CCBs should be used with caution in these patient populations.
Author Disclosures: J.J. Doyle: None. A.J. Doyle: None. N.K. Wilson: None. J.P. Habashi: None. D. Bedja: None. R.E. Whitworth: None. M.E. Lindsay: None. L. Myers: None. N. Huso: None. S. Bachir: None. D. Huso: None. D.P. Judge: None. H.C. Dietz: None.
- © 2014 by American Heart Association, Inc.