Giovanni Battista Pinna

Combination therapy with warfarin plus clopidogrel improves outcomes in femoropopliteal bypass surgery patients

BACKGROUND Patients having undergone femoropopliteal bypass surgery remain at significant risk of graft failure. Although antithrombotic therapy is of paramount importance in these patients, the effect of oral anticoagulation therapy (OAT) on outcomes remains unresolved. We performed a randomized, prospective study to assess the impact of OAT plus clopidogrel vs dual antiplatelet therapy on peripheral vascular and systemic cardiovascular outcomes in patients who had undergone femoropopliteal bypass surgery. METHODS Three hundred forty-one patients who had undergone femoropopliteal surgery were enrolled and randomized: 173 patients received clopidogrel 75 mg/d plus OAT with warfarin (C + OAT), and 168 patients received dual antiplatelet therapy with clopidogrel 75 mg/d plus aspirin 100 mg/d (C + acetylsalicylic acid [ASA]). Study end points were graft patency and the occurrence of severe peripheral arterial ischemia, and the incidence of bleeding episodes. RESULTS Follow-up ranged from 4 to 9 years. The graft patency rate and the freedom from severe peripheral arterial ischemia was significantly higher in C + OAT group than in C + ASA group (P = .026 and .044, respectively, Cox-Mantel test). The linearized incidence of minor bleeding complications was significantly higher in C + OAT group than in C + ASA group (2.85% patient-years vs 1.37% patient-years; P = .03). The incidence of major adverse cardiovascular events, including mortality, was found to be similar (P = .34) for both study groups. CONCLUSIONS In patients who have undergone femoropopliteal vascular surgery, combination therapy with clopidogrel plus warfarin is more effective than dual antiplatelet therapy in increasing graft patency and in reducing severe peripheral ischemia. These improvements are obtained at the expenses of an increase in the rate of minor anticoagulation-related complications.

Endothelial Nitric Oxide Synthase Expression in Postmenopausal Women: A Sex-Specific Risk Factor in Coronary Surgery

BACKGROUND After coronary artery bypass graft surgery, older women have less favorable clinical outcome and lower conduit patency compared with men. This less favorable outcome can be in part ascribed to impaired endothelium-derived nitric oxide (eNOS) production. This study evaluated endothelial nitric oxide synthase expression in internal mammary artery from postmenopausal women undergoing coronary artery bypass graft surgery. METHODS Internal mammary artery segments were obtained from 20 postmenopausal woman and 20 matched male patients. Twenty more segments from younger patients were used as controls. Expression of eNOS messenger RNA in internal mammary artery endothelial cells were evaluated by polymerase chain reaction and real-time quantitative reverse transcription polymerase chain reaction. The eNOS protein level was assayed by Western blot. Vascular dynamics of specimens were evaluated by organ chamber methodology. RESULTS In postmenopausal women, the band of messenger RNA for eNOS was reduced by 37.4% and by 25.2%, respectively, compared with matched men and the control group (62.6%±4.8% versus 74.8%±5.3%, p<0.001). In comparison with the control group lane, the eNOS protein immunoreactive band was 44.2% decreased in postmenopausal women and 34.5% decreased in matched men, and was significantly decreased in postmenopausal women as compared with matched men (55.8%±4.6% versus 65.5%±5.2%, p<0.001). Nitric oxide-mediated vasomotor dynamics were consistent with reduced eNOS production. CONCLUSIONS Internal mammary artery endothelial cells from women after menopause undergoing coronary surgery have impaired expression of messenger RNA for eNOS and reduced eNOS levels. Reduced bioactivity of nitric oxide translates into impaired endothelial metabolism that could contribute to worse surgical outcome.

Individualized strategy for clopidogrel suspension in patients undergoing coronary surgery: is it the best choice?

We read with interest the recent article by Gielen et al. and congratulate the authors on this timely study [1]. The study processed a number of patients divided into three groups according to the use of antiplatelet medication within 10 days prior to surgery: (i) acetylsalicylic acid (ASA) only, (ii) ASA + clopidogrel or (iii) no antiplatelet medication. To assess the optimal stop day, the authors analysed the amount of blood loss within 48 h after the operation by a series of multiple linear regression models, one for each preoperative day (from Day −10 up to −1). They concluded that there is no clinically relevant effect on blood loss, indicating an optimal day of withdrawal for ASA alone or in combination with clopidogrel. Nonetheless, the suspension of clopidigrel 2 days before surgery resulted in the reduction of percentage of patients receiving platelet transfusions, especially in the ASA + clopidogrel group. The authors are to be commended for taking the initiative to challenge the current guidelines by the evidence that discontinuation at a later day (−4 till −1) is not life threatening and does not significantly impact the postoperative blood loss and the amount of blood transfusions required. As recommended by European Society of Cardiology/European Association for Cardio-Thoracic Surgery guidelines on myocardial revascularization, preoperative clopidogrel should be suspended at least 5 days before surgery in elective patients referred for coronary artery bypass graft (CABG) surgery to reduce bleeding, usage of blood products and related complications [2]. However, guidelines have not taken into account the wide interindividual variability in recovery time after clopidogrel withdrawal, the wide range of individual responses to clopidogrel and the synergistic effect of ASA + clopidogrel in terms of the degree of platelet inhibition [3]. As a consequence, a different approach from current guidelines could be required to determine the optimal time for CABG surgery, especially in those patients with acute coronary syndrome who need urgent surgery and are exposed to antiplatelet therapy with ASA + clopidogrel or clopidogrel alone. In our recent case–control study carried out on patients undergoing CABG who were assuming clopidogrel, we evaluated the possibility of determining the time of preoperative clopidogrel discontinuation using an individualized point-of-care platelet function measurement [4]. Our results showed that monitoring platelet function provides an objective guideline to determine a flexible timing of surgery. This individualized strategy reduced the postoperative bleeding and the consumption of blood products. Finally, it should be emphasized that we identified a number of patients with normal platelet function despite being on an adequate dosage of clopidogrel (clopidogrel-resistant) and patients who had a fast recovery of platelet function after discontinuation of clopidogrel (within 2–3 days). In contrast, 20% of patients displayed persistent platelet inhibition and required from 6 to 8 days for complete recovery of platelet function after clopidogrel discontinuation. In conclusion, according to suggestions by the 2011 Blood Conservation Clinical Practice Guidelines from the Society of Thoracic Surgeons/Society of Cardiovascular Anesthesiologists, we believe that the point-of-care guided preoperative administration/discontinuation of antiplatelet agent could be indicated for an individual approach to patients with the aim to reduce both bleeding and adverse events compared with the current practice of unselected timing [5].

Endovascular Treatment of Distal Aortic Arch Aneurysm Associated with Coarctation of Aorta in a Jehovah's Witness

Late aneurysm formation in the proximal aorta or distal aortic arch is a recognized sequela of untreated stenosis of the aortic isthmus and is associated with substantial risk of aortic rupture. We describe the case of a 44-year-old man with untreated coarctation of the aorta who presented with a prestenotic dissecting thoracic aortic aneurysm. He declined surgery because he was a Jehovahs Witness. Instead, we performed emergency endovascular aortic repair in which 2 stent-grafts were placed in the descending aorta. Our experience suggests that this procedure is a useful and safe alternative to open surgery in patients who have aneurysms associated with coarctation of the aorta.

Antiplatelet therapy suspension in patients undergoing coronary surgery for acute coronary syndrome: Is point-of-care guided strategy the best choice?

In their recent publication Nagashima and colleagues evaluated the impact of recent exposure to dual antiplatelet therapy (DAPT) with aspirin and oral adenosine diphosphate (ADP)-receptor antagonists (clopidogrel or ticlopidine) before urgent coronary artery bypass graft (CABG) on increased risk of bleeding complications in Japanese patients with acute coronary syndromes (ACS) [1]. We read with interest the article and congratulate the authors on this original and timely study. The authors processed 130 consecutive patients with ACS divided into two groups according to the use of antiplatelet medication prior to surgery: 30 patients with preoperative thienopyridine exposure within 5 days and 100 patients without exposure. All patients continued to receive aspirin 100 mg/day until surgery. They concluded that preoperative DAPT increases the risk of CABG-related major bleeding in Japanese patients with ACS undergoing urgent CABG. The authors are to be commended for taking the initiative to challenge the current guidelines given that no data are available on Japanese patients [2]. In our randomized controlled study carried on Caucasian patients undergoing CABG for ACS who were receiving clopidogrel alone or in addition to aspirin, we showed a wide interindividual variability in recovery time after clopidogrel withdrawal, a large range of individual responses to clopidogrel, and a synergistic effect of aspirin plus clopidogrel in terms of degree of platelet inhibition [3]. On this basis, in our recent case–control study we analyzed the possibility to guide the time of preoperative clopidogrel discontinuation using an individualized point-of-care platelet function measurement and we suggested a different, individualized, approach than current guidelines to determine the optimal time for CABG surgery, especially in those patients who need urgent surgery [4]. Our results showed that monitoring platelet function provided an objective guideline to determine a flexible timing of surgery. This individualized strategy reduced the postoperative bleeding and the consumption of blood products in our experience. Finally,