Title: A Double-Blind, Randomized Study on Prevention and Existence of a Rebound Phenomenon of Platelets After Cessation of Clopidogrel Treatment
Topic: Interventional Cardiology
Date Posted: 2/1/2010 5:00:00 PM
Author(s): Sibbing D, Stegherr J, Braun S, et al.
Citation: J Am Coll Cardiol 2010;55:558-565.
Clinical Trial: No
Study Question: What is the evidence that a platelet rebound exists, and can it be attenuated by clopidogrel tapering?
Methods: Patients (n = 69) receiving clopidogrel treatment due to prior drug-eluting stent placement and planning to stop clopidogrel were recruited in a double-blind, randomized trial. Patients were randomized to either receive a prespecified tapering regimen (tapering group; n = 35) for 4 weeks with complete discontinuation of clopidogrel thereafter or continue a daily clopidogrel intake for 4 more weeks with abrupt discontinuation afterwards (off group; n = 34). Platelet aggregation (PA) was assessed with light transmission aggregometry (LTA) and multiple electrode aggregometry (MEA) simultaneously at study inclusion and at weeks 2 to 8 after randomization. The primary endpoint was the highest value of adenosine diphosphate–induced PA measured with LTA in the weeks after complete cessation of clopidogrel in both groups.
Results: The highest values of adenosine diphosphate–induced PA after complete cessation of clopidogrel were similar between both groups (p = 0.21 with LTA, and p = 0.55 with MEA).
Conclusions: The authors concluded that tapering of clopidogrel does not result in lower platelet aggregation values after clopidogrel withdrawal.
Perspective: The primary finding of the study is that a tapering of clopidogrel treatment, as compared with abrupt cessation of the drug, does not result in significantly lower platelet aggregation values in the time period after complete cessation of clopidogrel treatment. Overall, the course of platelet aggregation values after clopidogrel cessation does not support the existence of a rebound phenomenon of platelets after discontinuation of clopidogrel. The clinical safety and efficacy of abrupt versus tapered interruption of chronic clopidogrel therapy after DES implantation is being addressed in the ISAR-CAUTION trial, and will provide additional clinical insight on the optimal method to discontinue clopidogrel therapy. Debabrata Mukherjee, M.D., F.A.C.C.
Title: Endothelial Function, Carotid-Femoral Stiffness, and Plasma Matrix Metalloproteinase-2 in Men With Bicuspid Aortic Valve and Dilated Aorta
Topic: Noninvasive Cardiology
Date Posted: 2/8/2010 5:00:00 PM
Author(s): Tzemos N, Lyseggen E, Silversides C, et al.
Citation: J Am Coll Cardiol 2010;55:660-668.
Clinical Trial: No
Study Question: What is the relationship between proximal aortic dilation and systemic vascular function in men with bicuspid aortic valve (BAV)?
Methods: Thirty-two men (median age 31 years [range 28-32 years]) with nonstenotic BAV were categorized into two subgroups according to proximal ascending aorta dimensions (nondilated ≤35 mm and dilated ≥40 mm, respectively). Sixteen healthy men were studied as control subjects. Flow-mediated dilation in response to hyperemia, and carotid–femoral pulse wave velocity were assessed, and peripheral blood was sampled for matrix metalloproteinases (MMP-2 and -9) and their tissue inhibitors (TIMP-1 and -2), respectively. Cardiac chamber and aortic dimensions were assessed by echocardiography and cardiac magnetic resonance imaging, respectively.
Results: Despite similar severity of aortic stenosis, and left ventricular mass and function, men with dilated aortas had blunted brachial flow-mediated vasodilation to hyperemia (5% [interquartile range (IQR) 4-6%] vs. 8% [IQR 7-9%] change, p = 0.001), higher carotid–femoral pulse wave velocity (9.3 cm/s [IQR 9-10 cm/s] vs. 7 cm/s [IQR 6.9-7.4 cm/s], p = 0.001), and significantly higher plasma levels of MMP-2 (1,523 [IQR 1,460-1,674] vs. 1,036 [IQR 962-1,167], p = 0.001) compared to men with BAV and nondilated aorta.
Conclusions: The authors concluded that young men with BAV and dilated proximal aortas manifest systemic endothelial dysfunction, increased carotid–femoral pulse wave velocity, and higher plasma levels of MMP-2. These observations could introduce new targets for screening and perhaps for therapeutic intervention.
Perspective: BAV is the most common congenital heart malformation, occurring in 1-2% of the population. In addition to valvular dysfunction, BAV is associated with dilatation of the aortic root, which can lead to aortic dissection and rupture. The reason for this association is not clear and does not appear to be related to the degree of valvular dysfunction. The current study demonstrates that systemic changes in vascular function and stiffness, along with evidence of increased metalloprotease activity, are present in subjects with BAV and root dilatation. Additional confirmatory studies in a broader population (including women and patients with more stenotic BAV), along with genome-wide analyses, may lead to identification of novel biomarkers and treatment strategies for patients with BAV. Daniel T. Eitzman, M.D., F.A.C.C.