Modifying effect of dual antiplatelet therapy on incidence of stent thrombosis according to implanted drug-eluting stent type

Aim To investigate the putative modifying effect of dual antiplatelet therapy (DAPT) use on the incidence of stent thrombosis at 3 years in patients randomized to Endeavor zotarolimus-eluting stent (E-ZES) or Cypher sirolimus-eluting stent (C-SES). Methods and results Of 8709 patients in PROTECT, 4357 were randomized to E-ZES and 4352 to C-SES. Aspirin was to be given indefinitely, and clopidogrel/ticlopidine for ≥3 months or up to 12 months after implantation. Main outcome measures were definite or probable stent thrombosis at 3 years. Multivariable Cox regression analysis was applied, with stent type, DAPT, and their interaction as the main outcome determinants. Dual antiplatelet therapy adherence remained the same in the E-ZES and C-SES groups (79.6% at 1 year, 32.8% at 2 years, and 21.6% at 3 years). We observed a statistically significant (P = 0.0052) heterogeneity in treatment effect of stent type in relation to DAPT. In the absence of DAPT, stent thrombosis was lower with E-ZES vs. C-SES (adjusted hazard ratio 0.38, 95% confidence interval 0.19, 0.75; P = 0.0056). In the presence of DAPT, no difference was found (1.18; 0.79, 1.77; P = 0.43). Conclusion A strong interaction was observed between drug-eluting stent type and DAPT use, most likely prompted by the vascular healing response induced by the implanted DES system. These results suggest that the incidence of stent thrombosis in DES trials should not be evaluated independently of DAPT use, and the optimal duration of DAPT will likely depend upon stent type (Clinicaltrials.gov number NCT00476957

Facilitated percutaneous coronary intervention (PCI) in patients with acute ST-elevation myocardial infarction: Comparison of prehospital tirofiban versus fibrinolysis before direct PCI

AIMS: Early start of treatment including coronary revascularization has been recognized as crucial variable in the outcome of acute ST-segment elevation myocardial infarction (STEMI). The lack of availability and the realisation that an optimum reperfusion strategy will need to incorporate mechanical reperfusion as part of that strategy has led to a great deal of interest in pharmacologic reperfusion combined with mechanical reperfusion or facilitated PCI. It is not clear whether GPIIb/IIIa-blockade or fibrinolysis better facilitates PCI. METHODS: We identified 138 patients who have been primarily treated by our mobile emergency care mobile from July 2001 until February 2003 with tirofiban or fibrinolysis. Seventy-nine patients had ST-elevation myocardial infarction (STEMI) and available angiograms within 24 h. RESULS: Forty-four patients had tirofiban (TIRO; 60.6 S.D. 11.4 years, 64% male) and 35 patients underwent fibrinolysis (FIB; 31.4% tenecteplase, 54.3% reteplase, 11.4% alteplase, 2.9% streptokinase; 58.8 S.D. 12.2 years, 80% male). Data were analyzed with respect to TIMI-flow and corrected frame count (cTFC) before and after PCI, bleeding complications at 30 days and long-term follow up for major adverse events (median 288 days; MACE: Death, hospitalized re-infarction, intracranial hemorrhage). Catheter films were re-analyzed by an investigator blinded to the prehospital therapy. Time from onset of symptoms to first medical contact was 1.98 h in TIRO compared to 0.5 h in FIB (p<0.001) and time from first prehospital medical contact to catheter was 1.46 h in the TIRO compared to 2.85 h in the FIB group (p<0.001). TIMI 3-flow before PCI was observed in 20.5% of TIRO and 62.9% in FIB (p<0.001). After PCI TIMI 3-flow was achieved in 90.5% and 90.0%, respectively (p=n.s.). Final cTFC was 24 in TIRO and 29 in FIB (p=n.s.). Visible thrombi were detected in 30.2% in TIRO and 23.5% in FIB (p=n.s.). Major bleeding occurred in one TIRO patient (fatal lung bleeding after ultima ratio abciximab on top of tirofiban), 2 patients (4.5%) received transfusions. In FIB 2 intracerebral hemorrhages, 5 transfusions (14.3%) and 3 pulmonary bleedings during mandatory ventilation were observed. After 30 days 4.5% in TIRO and 22.9% in FIB had MACE (p=0.015). During long-term follow up the primary endpoint was observed in 4.5% of TIRO and 28.6% (p=0.003) of FIB. Two patients died in TIRO and 9 patients in FIB. CONCLUSIONS: We conclude that (1) prehospital start of tirofiban for facilitated PCI is safe and effective if administered by experienced emergency physicians; (2) routine fibrinolysis should be limited to areas where catheter based therapy is not available within 90 min and (3) fibrinolysis should be given for facilitated PCI in randomized trials only at the moment

Variability and accuracy of coronary CT angiography including use of iterative reconstruction algorithms for plaque burden assessment as compared with intravascular ultrasound-an ex vivo study

OBJECTIVES: To systematically assess inter-technique and inter-/intra-reader variability of coronary CT angiography (CTA) to measure plaque burden compared with intravascular ultrasound (IVUS) and to determine whether iterative reconstruction algorithms affect variability. METHODS: IVUS and CTA data were acquired from nine human coronary arteries ex vivo. CT images were reconstructed using filtered back projection (FBPR) and iterative reconstruction algorithms: adaptive-statistical (ASIR) and model-based (MBIR). After co-registration of 284 cross-sections between IVUS and CTA, two readers manually delineated the cross-sectional plaque area in all images presented in random order. RESULTS: Average plaque burden by IVUS was 63.7 ± 10.7% and correlated significantly with all CTA measurements (r = 0.45-0.52; P  0.05). Increased overestimation was associated with smaller plaques, eccentricity and calcification (P  0.05). CONCLUSION: In ex vivo coronary arteries, plaque burden by coronary CTA had extremely low inter-/intra-reader variability and correlated significantly with IVUS measurements. Accuracy as well as reader reliability were independent of CT image reconstruction algorithm. KEY POINTS: • IVUS is deemed the gold standard in-vivo coronary plaque assessment • But coronary CT angiography findings correlate strongly with IVUS results • Coronary CT angiography now allows plaque quantification close to IVUS • Iterative image reconstruction algorithms do not alter accuracy or reproducibility • Plaque quantification is more challenging in smaller eccentric calcified lesions

Synthesis of novel Bi-, Tri-, and tetracyclic nucleosides by reaction of a common cyclic enamine derived from TSAO-T with nucleophiles

We report here the efficient regio-and stereoselective synthesis of new polycyclic nucleosides using a common cyclic enamine (7) as the starting material. In fact, the reaction of 7, easily prepared by reaction of 5¢-O-Tosyl TSAO-T under basic nonnucleophilic conditions (potassium carbonate), with different classes of nucleophiles, for example, nitrogen-, oxygen-, sulfur-, and carbon-based nucleophiles, or with amino acids afforded, with total regio-and stereoselectivity, new bi-, tri-, and tetracyclic nucleosides. This straighforward route represents an original and unambiguously regio- and stereoselective pathway to these compounds. Some of these polycyclic nucleosides may be useful intermediates for a second series of reactions that may lead to the generation of structurally new nucleosides.We thank Susana Ruiz and Marı´a Jose´ Galeote for their excellent technical as- sistance. We thank the Ministry of Education of Spain for grants to C.C. and M.-C.B. The Spanish Ministerio de Ciencia y Tecnologı´a (Project SAF2003-07219-C02- 01) and the European Commission (Projects QLK2-CT- 2000-00291 and HPAW-CT-2002-90001) are acknowl- edged for their financial support.Peer reviewe