Why the study?
Do calcium channel blockers increase the risk of aortic dissection and need for aortic surgery in patients with Marfan syndrome?
Do calcium channel blockers increase the risk of aortic dissection and need for aortic surgery in patients with Marfan syndrome?
Calcium channel blockers may be deleterious in Marfan syndrome, accelerating aortic aneurysm progression and increasing the risk of dissection and need for surgery.
May warrant CCB caution in Marfan syndrome; hypothesis-generating and leaves open need for prospective trials.
Calcium channel blockers (CCBs) are prescribed to patients with Marfan syndrome for prophylaxis against aortic aneurysm progression, despite limited evidence for their efficacy and safety in the disorder. Unexpectedly, Marfan mice treated with CCBs show accelerated aneurysm expansion, rupture, and premature lethality. This effect is both extracellular signal-regulated kinase (ERK1/2) dependent and angiotensin-II type 1 receptor (AT1R) dependent. We have identified protein kinase C beta (PKCβ) as a critical mediator of this pathway and demonstrate that the PKCβ inhibitor enzastaurin, and the clinically available anti-hypertensive agent hydralazine, both normalize aortic growth in Marfan mice, in association with reduced PKCβ and ERK1/2 activation. Furthermore, patients with Marfan syndrome and other forms of inherited thoracic aortic aneurysm taking CCBs display increased risk of aortic dissection and need for aortic surgery, compared to patients on other antihypertensive agents.
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Doyle et al. (2015) studied this question.
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