Alexander Joost

Loading With 600 mg Clopidogrel in Patients With Coronary Artery Disease With and Without Chronic Clopidogrel Therapy

Background—It is not known whether further suppression of platelet function can be achieved with clopidogrel beyond that provided by currently recommended loading and maintenance doses. We performed a comparative assessment of the antiplatelet effects of a 600-mg loading dose of clopidogrel given to patients with and without chronic clopidogrel therapy. Methods and Results—Those eligible for this prospective study were aspirin-treated patients with suspected or documented coronary artery disease admitted to hospital for coronary angiography. Two series of 20 consecutive patients each were assessed in this study. The first series included patients who had never received clopidogrel (first-use group); the second series included patients on chronic therapy with a daily dose of 75 mg clopidogrel for ≥1 month (chronic therapy group). Blood samples were drawn before and 6 hours after oral administration of 600 mg clopidogrel for aggregometry and flow cytometry studies. In the first-use group, loading with 600 mg clopidogrel inhibited ADP 5 &mgr;mol/L–induced platelet aggregation from 90±9% to 51±19% (P<0.001). In the chronic therapy group, loading with 600 mg clopidogrel yielded further inhibition of ADP 5 &mgr;mol/L–induced platelet aggregation in addition to that achieved by the maintenance dose of 75 mg/d, from 52±14% to 33±12% (P<0.001). In both groups, 600 mg clopidogrel loading significantly inhibited ADP-induced expression of glycoprotein IIb/IIIa and P-selectin receptors. Conclusions—Further platelet inhibition can be achieved with clopidogrel in addition to that provided by currently recommended loading and maintenance doses. Higher doses may be warranted after assessment of their clinical efficacy and safety.

Vascular effects of paclitaxel following drug-eluting balloon angioplasty in a porcine coronary model: the importance of excipients

AIMS The vascular effects of drug- eluting balloon (DEB) deployment in the absence of coronary stents have not been characterised. This study evaluated potential vascular effects of paclitaxel-coated angioplasty balloons using different excipients in the absence of additional stents. METHODS AND RESULTS A total 45 porcine arteries were treated with paclitaxel-coated DEBs using four different excipients (all 3.0 µg/mm2): A) iopromide (n=9), B) ATEC excipient (n=8), C) BTHC excipient (n=10), D) lecithine excipient (n=10). Uncoated bare angioplasty balloons served as controls (n=8). Histology, histomorphometry, and quantitative angiography analysis were performed 28 days following intervention. Tissue concentrations of paclitaxel were measured in selected animals using BTHC excipient (n=39 arteries) and reached maximum concentrations of 165 ng/mg 30 min after delivery in coronary target tissue. There were no differences in efficacy endpoints using histomorphology or quantitative angiography between groups. In contrast, however, treatment with DEBs using BTHC excipient or iopromide was associated with increased fibrin deposition and inflammation indicating delayed vascular healing. DEBs using lecithin excipient or uncoated angioplasty balloons did not induce any comparable vascular effects. CONCLUSIONS Effective excipients are necessary to accomplish successful balloon facilitated paclitaxel delivery, which is associated with delayed vascular healing as a sign of successful drug transfer. The potential of DEBs to diminish restenosis following angioplasty may be insufficient in the absence of additional stents.

Drug eluting balloons for the treatment of coronary artery disease: What can we expect?

Drug-eluting balloons (DEBs) represent an enhancement of the therapeutic repertoire for the interventional cardiologist. The therapeutic concept of DEBs is promising, notably on the basis of initial studies in patients with diffuse in-stent restenosis (ISR). At present, however, a number of questions regarding long-term efficacy and safety remain, specifically in indications other than diffuse ISR. The results of the evaluation of different substances, balloon systems and clinical indications will determine the long-term success of DEBs.

A randomized, parallel group, double-blind study of ticagrelor compared with aspirin for prevention of vascular events in patients undergoing coronary artery bypass graft operation: Rationale and design of the Ticagrelor in CABG (TiCAB) trial: An Investigator-Initiated trial

BACKGROUND For patients with coronary artery disease undergoing coronary bypass surgery, acetylsalicylic acid (ASA) currently represents the gold standard of antiplatelet treatment. However, adverse cardiovascular event rates in the first year after coronary artery bypass grafting (CABG) still exceed 10%. Graft failure, which is predominantly mediated by platelet aggregation, has been identified as a major contributing factor in this context. Therefore, intensified platelet inhibition is likely to be beneficial. Ticagrelor, an oral, reversibly binding and direct-acting P2Y12 receptor antagonist, provides a rapid, competent, and consistent platelet inhibition and has shown beneficial results compared with clopidogrel in the subset of patients undergoing bypass surgery in a large previous trial. HYPOTHESIS Ticagrelor is superior to ASA for the prevention of major cardiovascular events within 1 year after CABG. STUDY DESIGN The TiCAB trial (NCT01755520) is a multicenter, phase III, double-blind, double-dummy, randomized trial comparing ticagrelor with ASA for the prevention of major cardiovascular events within 12 months after CABG. Patients undergoing CABG will be randomized in a 1:1 fashion to either ticagrelor 90 mg twice daily or ASA 100 mg once daily. The study medication will be started within 24 hours after surgery and maintained for 12 months. The primary end point is the composite of cardiovascular death, myocardial infarction, stroke, and repeat revascularization at 12 months after CABG. The sample size is based on an expected event rate of 13% of the primary end point within the first 12 months after randomization in the control group, a 2-sided α level of .0492 (to preserve the overall significance level of .05 after planned interim analysis), a power of 0.80%, 2-sided testing, and an expected relative risk of 0.775 in the active group compared with the control group and a dropout rate of 2%. According to power calculations based on a superiority design for ticagrelor, it is estimated that 3,850 patients should be enrolled. SUMMARY There is clinical equipoise on the issue of optimal platelet inhibition after CABG. The TiCAB trial will provide a pivotal comparison of the efficacy and safety of ticagrelor compared with ASA after CABG.

Candesartan cilexetil: an update

Introduction: Candesartan cilexetil is one of the most often-used first-line drugs regarding the management of arterial hypertension. Moreover, this drug has proven its effectiveness in chronic heart failure and exerts beneficial effects in diabetes, stroke, dementia and atrial fibrillation. Areas covered: This review focuses on the use of candesartan cilexetil in Phase II and Phase III trials and their implications for clinical usage in the treatment of arterial hypertension and heart failure. The usage of candesartan cilexetil in patients with stroke, migraine or atrial fibrillation, hypertrophy obstructive or nonobstructive cardiomyopathy and diabetic or non diabetic renal diseases will be discussed. Relevant publications were identified by an extensive Medline search. Expert opinion: Candesartan cilexetil is a highly effective ARB for the treatment of arterial hypertension and heart failure. Also, recent trials have suggested beneficial effects in diabetic patients, patients with nondiabetic renal diseases, stroke, migraine and atrial fibrillation.

Anticoagulation in Patients with Heparin-Induced Thrombocytopenia undergoing Percutaneous Coronary Angiography and Interventions

The administration of heparins (unfractionated or fractionated) represents the current standard as anticoagulant treatment during percutaneous coronary intervention in different clinical settings (elective cases and acute coronary syndrome). Since the incidence of heparin-induced thrombocytopenia (HIT) is expected to range between 0.1 and 5%, the application of an appropriate anticoagulant agent has become a mandatory issue. This review will provide current pathophysiological insights of HIT as well as contemporary alternative anticoagulant strategies during PCI in patients with or at risk of HIT.

Late perforation of the ventricular ICD lead causes a pericarditis like ECG in a patient with Brugada syndrome

A 53-year-old male patient was admitted to the referring hospital because of an assumed acute coronary syndrome with syncope. Myocardial infarction was ruled out. The ECG revealed ST-segment elevation in the right precordial leads (Fig. 1). Coronary angiography excluded a coronary heart disease. Later on, ST-segment elevations diminished. A pharmacological test with 70 mg ajmalin i.v. showed pronounced ST-segment elevation in the right ventricular leads (Fig. 2). Due to the assumed Brugada syndrome (BrS), an electrophysiological study was performed. A monomorphic ventricular tachycardia could be induced. These findings led to the diagnosis of a BrS and to the implantation of a dual chamber ICD (Biotronik®Lumax 340 DR-T (Berlin, Germany) with a Kentrox RV-lead). The patient was subsequently discharged from the hospital. After two months the ICD system showed a regular function. Oneweek later the patientwas readmitted to the referring hospital due to acute respiratory thoracic pain. Myocardial ischemia was again ruled out. The control of the ICD

TCT-485 A simple strategy to significantly reduce the “door-to-balloon” time in patients with acute ST-elevation myocardial infarction

The in-hospital delay between admission and successful coronary reperfusion (“door- to- balloon” time interval, DTB) in patients with a diagnosis of STEMI is a predictor of mortality. Reducing the DTB time below 90 minutes- as suggested in current guidelines- represents a major challenge for