Optimal pharmacotherapy is essential to realize the bestoutcomes in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). In this regard, effectively restoring reperfusion and maintaining the patency of the infarct artery after stenting requires a balance between the haemorrhagic risks and the ischaemic benefits of anticoagulant and antiplatelet agents. Over the last three decades, as the principal device used for primary PCI has evolved from balloon angioplasty to bare metal stents to drug-eluting stents, parallel advances have occurred in antithrombotic and antiplatelet regimens, from unfractionated heparin (UFH) alone, toUFHplus a glycoprotein IIb/IIIa inhibitor (GPI), to bivalirudin with provisional (bailout) GPI use, and from ticlopidine and clopidogrel to prasugrel and ticagrelor (on a background of aspirin). Given the time, complexity, and costs of performing appropriately powered randomized trials, clinical practice has progressed faster than the evidence base required to inform optimal drug and device usage for all possible drug and device permutations. Unfractionated heparin, a heterogeneous mixture of polysaccharides of varying chain lengths, while familiar and inexpensive, has numerous shortcomings, which become most clinically apparent in acute coronary syndromes (ACS). Unfractionated heparin has an indirect mechanism of action (binding to and activation of antithrombin III, the amount of which varies in disease states) and has limited activity against clot-bound thrombin. Non-specific protein and cellular binding of UFH results in variable biological activity and can result in heparin-induced thrombocytopenia and thrombosis. Moreover, UFHbinds to the glycoprotein IIb/IIIa receptor, thereby paradoxically activating platelets. Kastrati and colleagues elegantly demonstrated that, despite pre-treatment with aspirin and clopidogrel, myocardial infarction rates in non-STEMI are substantially reduced after PCI with abciximab. Meta-analysis of eight randomized trials in 3949 patients with STEMI undergoing PCI demonstrated that the addiion of abciximab to UFH reduced the 30 day odds of re-infarction by 37% (P , 0.001) and the 6–12 month odds of mortality by 28% (P 1⁄4 0.01). In the largest such study, CADILLAC, 30 day stent thrombosis was also reduced with abciximab plus UFH vs. UFH alone (P 1⁄4 0.01). These benefits more than offset the increased rates of bleeding and thrombocytopenia that may occur with GPI. As such, aspirin, clopidogrel, and UFH plus GPI became the preferred regimento supportprimary PCI inSTEMI, used in .90%ofpatients in the USA and in the majority of patients in Europe. This regimen remained the standard for more than a decade until challenged by the direct thrombin inhibitor bivalirudin, a rapidly reversible agent (half-life 25 min), which overcomes many of the limitations of UFH. Specifically, bivalirudin does not require antithrombin III for activation, is able to inhibit fibrin-found thrombin, has predictable biological activity and dosing, does not cause thrombocytopenia or activate platelets, and indeed, blocks both collagenand thrombin-induced platelet activation. A series of multicentre randomized PCI trials across the spectrum of coronary artery disease has demonstrated that in comparison to UFH plus GPI, bivalirudin with provisional GPI use results in similar rates of composite ischaemic events,with 40–50% reductions inmajorbleedingand thrombocytopenia. 12 The EuroMax trial confirmed that the bleeding benefits of bivalirudinarepresent inpatients treatedwith radial aswell as femoral access, which is not surprising given that the majority of major bleeding events after PCI in ACS are not access site related. Morevoer, in the largest randomized primary PCI trial to date, anticoagulation with bivalirudin in comparison to UFH plus GPI resulted in reduced cardiac and all-cause mortality at 30 days, benefits which were sustained to 3 years, reflecting both haematological and nonhematological benefits of bivalirudin. As a result, in many countries bivalirudin has supplanted UFH plus GPI as the preferred regimen to support primary PCI in STEMI. How can the results with bivalirudin be improved further? One glaring deficiency of bivalirudin monotherapy in primary PCI during STEMI (which has not been observed in other settings) was first noted in the HORIZONS-AMI trial, and subsequently confirmed in EuroMax; stent thrombosis, occurring within the first 4 h after the

A 67-year-old female was admitted to our hospital exhibiting chest pain and dyspnea that occurred immediately after an exercise-induced syncope. A priori the clinical symptoms, ECG ( Panel A ), and myocardial biomarkers were indicative for an acute coronary syndrome (troponin I: 7.35 ng/mL). Coronary angiogram ruled out both coronary artery disease and coronary …

Background Chronic kidney disease (CKD) has an adverse impact on survival of patients with coronary artery disease and is associated with poor outcomes after percutaneous coronary intervention (PCI). Although small randomized, controlled clinical trials showed a reduced target vessel revascularization rate and a good safety profile for sirolimus-eluting coronary stents (SES), safety data need to be confirmed in clinical practice. Therefore, the data of the German DES.DE registry were evaluated to obtain acute and long-term data of this high-risk subgroup.Methods The prospective multicenter German DES.DE registry enables to monitor the therapeutic outcome of different drug-eluting stents in the context of the German Health Care System. Baseline clinical and angiographic characteristics as well as one-year-follow-up data were recorded. From October 2005 to October 2006, 6,384 patients were enrolled at 98 DES.DE sites and stratified according to kidney disease progression: normal and impaired renal function and patients under chronic hemodialysis.Results CKD was associated with several acute and chronic medical conditions and suffer from significantly more cardiac and cerebrovascular events after PCI as compared to patients without CKD. One-year-follow-up showed a significantly increased risk of restenosis and bleeding complications in patients with impaired renal function, especially in hemodialysis patients.Conclusions Impaired renal function in patients undergoing DES stenting carries an independent risk factor for restenosis and bleeding.

BACKGROUND After exposure to contrast medium (CM), about 10% of patients will develop contrast medium-induced nephropathy (CIN), with severe consequences for their prognosis. Although numerous studies evaluated risk factors for CIN development, it is still a matter of debate whether treatment with angiotensin-converting enzyme inhibitors (ACE-I) or AT-1 blockers increases the frequency of CIN after exposure to CM or not. METHODS We performed a prospective, single-centre study (January 2001-July 2004) to compare different treatments for CIN prevention. Creatinine levels within 72 h after CM application and in-hospital outcomes were documented. The impact of RAAS blockade on the frequency of CIN was assessed retrospectively. RESULTS Four hundred twelve patients were included (83.5% men, 29.1% diabetes mellitus, 74.6% hypertension). Of these, 269 patients (65.3%) were taking ACE-I (n = 236) or AT-1 blockers (n = 33). There were no significant differences in mean age (P = 0.075), creatinine levels (P = 0.113), gender (P = 0.281), diabetes mellitus (P = 0.172) or left ventricular ejection fraction (P = 0.09) between patients treated or not treated with RAAS blockade. Univariate analyses concerning development of CIN depending on treatment with RAAS blockade within 72 h found CIN to be significantly higher in patients treated with RAAS blockade (11.9 vs 4.2%, P = 0.006). Multivariate analyses (logistic regression) identified RAAS blockade to be an independent predictor of CIN (odds ratio 3.082, 95% confidence interval 1.234-7.698, P = 0.016). CONCLUSION Patients treated with RAAS blockade before exposure to CM develop significantly more often CIN within 72 h. Even after adjustment for confounding comorbidities, treatment with ACE-I or AT-1 blockers turned out to be an independent risk predictor.

BACKGROUNDOf patients exposed to contrast medium (CM), 10% will develop contrast medium-induced nephropathy (CIN). Many studies have assessed potential risk factors for CIN. There are limited date concerning the influence of gender on frequency of CIN.METHODSFrom January 2001 to July 2004, a prospective trial was performed to compare different treatments for CIN prevention. Creatinine levels (72 hours) were assessed, as well as in-hospital and long-term outcome. CIN was defined as in an increase of > or =25% or >0.5 mg/dL compared with baseline creatinine. The frequency of CIN in women and men was determined retrospectively.RESULTSFour hundred twelve patients (67.1 +/- 10.2 years, 68 women) were randomized for different treatment strategies. Univariate analyses identified higher age (p = 0.031), diabetes (p = 0.03), decreased estimated glomerular filtration rate (eGFR) (p < 0.001), lower hemoglobin levels (p = 0.001), use of angiotensin-converting enzyme inhibitors (ACEI) (p = 0.004) and loop diuretics (p = 0.011), the amount of CM given (p < 0.001), and female gender to be associated with the occurrence of CIN within 72 hours. The frequency of CIN within 72 hours after CM administration was significantly higher in women than in men (p = 0.016). When CIN-associated factors were compared between women and men, women were older (69.8 vs. 66.5 years, p = 0.014) and had lower hemoglobin levels (12.6 vs. 13.8 g/dL, p < 0.001) and eGFR (35 vs. 49 mL/min, p < 0.001), suffered more often from diabetes (37% vs. 29%, p = 0.09), and had medication more frequently with loop diuretics (50% vs. 36%, p = 0.036) but not ACEI (56% vs. 57%, ns). The amount of CM given was identical (189 vs. 189 mL, ns). Multivariate analysis found female gender not to be an independent predictor of CIN (odds ratio [OR] 1.48, 95% confidence interval [CI] 0.72-3.02).CONCLUSIONSWomen are significantly more likely than men to suffer from CIN. This higher rate of CIN was confounded by unfavorable comorbidities, as found by univariate and multivariate analyses.