**5. Conclusion**

234 Perioperative Considerations in Cardiac Surgery

Pretreatment with ASA as well as with TPs significantly lower (up to 70%) the incidence of early acute thrombotic occlusions after PTCA [8]. Since the additional administration of FRAs to ASA and/or clopidogrel as well as to standard therapy including anticoagulants, nitrates, and beta-blockers, further reduce (40%) early cardiac incidents (partly, however, at cost of increased bleeding events [88-105]), the ACC/AHA guidelines recommend the addition of a FRA to ASA and heparin to patients in whom catheterization and coronary intervention are planned [106]. Furthermore, eptifibatide or tirofiban together with ASA and heparin should be given to patients with continuing ischemia or elevated troponin levels, in whom invasive management is not planned. Clopidogrel administered before cardiac catheterization enhances perioperative bleeding, if angiography reveals that bypass grafting is required rather than percutaneous coronary intervention. Thus, the American College of Chest Physicians (ACCP) guidelines recommend withholding clopidogrel until the coronary anatomy is determined [107]. Despite the efficacy of antiplatelet therapy concerning early thrombotic occlusions after PTCA, studies on the prevention of later re-stenosis (> 6 month) were disappointing [108,109]. Due to an excessive fibroproliferative response, up to 30% of PTCA patients developed recurrent ischemia and re-stenosis [110]. Only the results of the TACTICS study [104] showed that in patients with ACS early invasive strategy combined with immediate administration of FRAs was significantly better concerning late vascular deaths than the "wait and see" approach. Patients with elevated troponin levels had the

2 million patients of Western Countries undergo coronary dilatation each year [77], and coronary stents are placed in over 90% of these patients [111]. One of the greatest fears is subacute stent thrombosis triggered within minutes to hours after coronary intervention by activated PLTs. Predictors for increased risk of re-thrombosis are elevated GP IIb-IIIa expression or PLT degranulation markers prior to PCI as well as high post-interventional PLT reactivity to ADP [112]. Thus, long-term antiplatelet therapy is mandatory for the

One of the first trials on stent thrombosis showed that ticlopidine (vs. anticoagulants) reduced the risk [113]. Thereafter, numerous clinical trials have demonstrated the superiority of dual antiplatelet therapy [114-116]. Based on these data, the American Heart Association/American College of Cardiology guidelines recommend ASA plus a 300 mg or 600 mg (better PLT inhibition) clopidogrel loading, followed by a 75 mg clopidogrel maintenance for 12 months for all patients undergoing PCI and/or stenting [117]. Recently, prasugrel demonstrated even higher efficiency than clopidogrel (plus 52%) irrespective of the clopidogrel loading dose: 300 mg [40] or 600 mg [39], however at cost of increased bleeding (2.4% vs. 1.8%, p=0.03) [40]. Moreover, the additional application of FRAs prior to PCI has significantly increased clinical outcomes as seen by improvements in early and late TIMI 3 flow rate, global left ventricular function, early re-stenosis, and recurrent ischemia [89,91,92,105,118,119] in spite of bleeding complications [92]. Abciximab could promote the re-establishment of the microcirculation, thus the functional recovery of the infarcted heart region. From the STOP-AMI trial [120] stenting + abciximab + dual antiplatelet therapy was superior over fibrinolysis with respect to myocardial salvage and the accumulation of death and thromboembolic complications for up to 6 months (p=0.02) and resulted in superior

*Percutaneous transluminal coronary angioplasty (PTCA)* 

greatest benefit from this strategy [8].

success of coronary stenting.

*Coronary stenting* 

Despite its efficacy, ASA is a relatively weak antiplatelet drug, and ADP receptor antagonists like clopidogrel are only marginally superior to ASA in the reduction of AMI and stroke. Furthermore, adverse ischemic events probably due to drug resistance remain a serious clinical problem. The combination of different antiplatelet substances may implicate additive properties and is proven to be beneficial for patients, in whom monotherapy is not sufficient (non-responders) or who implicate a high thrombotic risk after coronary interventions. Given the predominate role of PLTs in the mechanism of stent thrombosis, dual antiplatelet therapy has reduced its incidence to less than 1.5% in most recent studies. Meanwhile, the combination of several (even three) antiplatelet drugs has become the standard of care in these situations. A future challenge, however, is to depict patients at especially high risk for post-interventional thrombotic complications, who may have additional benefit from the optimal antiplatelet therapy, probably with new antiplatelet regimens.
