760-4 Initial Multicenter Experience with Therapeutic Ultrasonic Coronary Angioplasty in Patients

Therapeutic ultrasonic (195 kHz) catheters with 1.2 or 1.7 mm ball tips for coronary angioplasty have recently been developed. During the first phase of a multi-center European trial (CRUSADE) this system was evaluated in 100 patients (86% male, mean age 57 years) with symptomatic coronary artery disease or acute myocardial infarction. Lesions were located in the LAD (n = 61), CX (n = 17), and RCA (n = 22); 62% were type B or C; 11 lesions were restenotic, 19 occlusive, 9 longer than 20 mm, 37 calcified, 18 thrombotic, and 15 collateralised.ResultsThe ultrasound catheter crossed 82/100 lesions, adjunctive balloon angioplastywas needed in 98 lesions. There was no death and myocardial infarction, or CABG in the first 24 hours. There was no perforation, but 2 acute vessel closures; intimal cleft or dissection was seen in 17 lesions of which 1 required stenting. Procedural success was obtained in 93%. At 24 hours 11/100 vessels were reoccluded. At 6 months angiographic follow-up in 51 patients restenosis (>50% stenosis) occured in 33%.ConclusionsTherapeutic ultrasound angioplasty is a feasible and safe new treatment modality. Adjunctive balloon angioplasty is regularly necessary. Preliminary experience suggests usefulness in lesions with visible thrombus, and undilatable or uncrossable lesions

Consistent Reduction in Periprocedural Myocardial Infarction With Cangrelor as Assessed by Multiple Definitions

BACKGROUND: Cangrelor is an intravenous P2Y12 inhibitor approved to reduce periprocedural ischemic events in patients undergoing percutaneous coronary intervention not pretreated with a P2Y12 inhibitor. METHODS: A total of 11 145 patients were randomized to cangrelor or clopidogrel in the CHAMPION PHOENIX trial (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition). We explored the effects of cangrelor on myocardial infarction (MI) using different definitions and performed sensitivity analyses on the primary end point of the trial. RESULTS: A total of 462 patients (4.2%) undergoing percutaneous coronary intervention had an MI as defined by the second universal definition. The majority of these MIs (n=433, 93.7%) were type 4a. Treatment with cangrelor reduced the incidence of MI at 48 hours (3.8% versus 4.7%; odds ratio [OR], 0.80; 95% confidence interval [CI], 0.67-0.97; P=0.02). When the Society of Coronary Angiography and Intervention definition of periprocedural MI was applied to potential ischemic events, there were fewer total MIs (n=134); however, the effects of cangrelor on MI remained significant (OR, 0.65; 95% CI, 0.46-0.92; P=0.01). Similar effects were seen in the evaluation of the effects of cangrelor on MIs with peak creatinine kinase-MB ≥10 times the upper limit of normal (OR, 0.64; 95% CI, 0.45-0.91) and those with peak creatinine kinase-MB ≥10 times the upper limit of normal, ischemic symptoms, or ECG changes (OR, 0.63; 95% CI, 0.48-0.84). MIs defined by any of these definitions were associated with increased risk of death at 30 days. Treatment with cangrelor reduced the composite end point of death, MI (Society of Coronary Angiography and Intervention definition), ischemia-driven revascularization, or Academic Research Consortium definite stent thrombosis (1.4% versus 2.1%; OR, 0.69; 95% CI, 0.51-0.92). CONCLUSIONS: MI in patients undergoing percutaneous coronary intervention, regardless of definition, remains associated with increased risk of death in the current era. Cangrelor compared with clopidogrel significantly reduces MI regardless of the definition. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT01156571

Efficacy and safety of cangrelor in patients with peripheral artery disease undergoing percutaneous coronary intervention – Insights from the CHAMPION program

Abstract Background Peripheral artery disease (PAD) is associated with an increased risk of ischemic events following percutaneous coronary intervention (PCI). More aggressive antiplatelet therapy may mitigate this risk. The present study evaluates the efficacy of cangrelor in patients with PAD undergoing PCI. Methods and results This is a pooled analysis from the CHAMPION PCI, CHAMPION PLATFORM, AND CHAMPION PHOENIX trials, evaluating cangrelor versus either clopidogrel or placebo in PCI patients. The occurrence of the primary endpoint of death, myocardial infarction, or ischemia-driven revascularization (IDR) was assessed in patients with and without PAD. GUSTO severe bleeding at 48 h was also evaluated. There were 1720 (7%) patients with PAD and 22,802 (93%) without PAD. After adjustment for differences in baseline variables, PAD patients, compared with those without PAD, experienced increased odds of the primary endpoint (OR [95% CI] = 1.27 [0.91, 1.77], P = 0.16) and GUSTO severe bleeding (OR [95% CI] = 3.24 [1.28, 8.21], P = 0.01). In PAD patients, the primary endpoint was 4.7% with cangrelor vs. 7.2% with clopidogrel (OR [95% CI] = 0.64 [0.42,0.96]); in patients without PAD the primary endpoint was 3.5% with cangrelor vs. 4.2% with clopidogrel (OR [95% CI] = 0.83 [0.72,0.95]), P-interaction 0.23. Among patients with or without PAD, there was no significant difference in the rate of GUSTO severe bleeding with cangrelor compared with control, P-interaction 0.86. Conclusions In a pooled analysis of the CHAMPION studies, PAD was associated with increased rates of ischemic and bleeding complications. Cangrelor reduced the odds of ischemic events, without increasing GUSTO severe bleeding. Clinical trial registration clinicaltrials.gov identifiers: CHAMPION PCI ( NCT00305162 ), CHAMPION PLATFORM ( NCT00385138 ), CHAMPION PHOENIX ( NCT01156571

NT-proBNP level before primary PCI and risk of poor myocardial reperfusion: Insight from the On-TIME II trial.

Background N-terminal fragment of the brain natriuretic peptide prohormone (NT-proBNP), a marker for neurohumoral activation, has been associated with adverse outcome in patients with myocardial infarction. NT-proBNP levels may reflect extensive ischemia and microvascular damage, therefore we investigated the potential association between baseline NTproBNP level and ST-resolution (STR), a marker of myocardial reperfusion, after primary percutaneous coronary intervention (pPCI).Methods we performed a post-hoc analysis of the On-TIME II trial (which randomized ST-elevation myocardial infarction (STEMI) patients to pre-hospital tirofiban administration vs placebo). Patients with measured NT-proBNP before angiography were included. Multivariate logistic-regression analyses was performed to investigate the association between baseline NTproBNP level and STR one hour after pPCI.Results Out of 984 STEMI patients, 918 (93.3%) had NT-proBNP values at baseline. Patients with STR 70% had higher NT-proBNP values compared to patients with complete STR (70%) [Mean +/- SD 375.2 +/- 1021.7 vs 1007.4 +/- 2842.3, Median (IQR) 111.7 (58.4-280.0) vs 168.0 (62.3-601.3), P < .001]. At multivariate logistic regression analysis, independent predictors associated with higher risk of poor myocardial reperfusion (STR < 70%) were: NT-proBNP (OR 1.17, 95%CI 1.041.31, P = .009), diabetes mellitus (OR 1.87, 95%CI 1.14-3.07, P = .013), anterior infarct location (OR 2.74, 95% CI 2.00-3.77, P < .001), time to intervention (OR 1.06, 95%CI 1.01-1.11, P = .021), randomisation to placebo (OR 1.45, 95%CI 1.05-1.99, P = .022).Conclusions In STEMI patients, higher baseline NT-proBNP level was independently associate with higher risk of poor myocardial reper fusion, suppor ting the potential use of NT-proBNP as an early marker for risk stratification of myocardial reperfusion after pPCI in STEMI patients

Self-consistent solution for the polarized vacuum in a no-photon QED model

We study the Bogoliubov-Dirac-Fock model introduced by Chaix and Iracane ({\it J. Phys. B.}, 22, 3791--3814, 1989) which is a mean-field theory deduced from no-photon QED. The associated functional is bounded from below. In the presence of an external field, a minimizer, if it exists, is interpreted as the polarized vacuum and it solves a self-consistent equation. In a recent paper math-ph/0403005, we proved the convergence of the iterative fixed-point scheme naturally associated with this equation to a global minimizer of the BDF functional, under some restrictive conditions on the external potential, the ultraviolet cut-off $\Lambda$ and the bare fine structure constant $\alpha$. In the present work, we improve this result by showing the existence of the minimizer by a variational method, for any cut-off $\Lambda$ and without any constraint on the external field. We also study the behaviour of the minimizer as $\Lambda$ goes to infinity and show that the theory is "nullified" in that limit, as predicted first by Landau: the vacuum totally kills the external potential. Therefore the limit case of an infinite cut-off makes no sense both from a physical and mathematical point of view. Finally, we perform a charge and density renormalization scheme applying simultaneously to all orders of the fine structure constant $\alpha$, on a simplified model where the exchange term is neglected.Comment: Final version, to appear in J. Phys. A: Math. Ge

Central Adjudication Identified Additional and Prognostically Important Myocardial Infarctions in Patients Undergoing Percutaneous Coronary Intervention

n/

The effect of age on outcomes of coronary artery bypass surgery compared with balloon angioplasty or bare-metal stent implantation among patients with multivessel coronary disease. A collaborative analysis of individual patient data from 10 randomized trials.

OBJECTIVES: This study sought to assess whether patient age modifies the comparative effectiveness of coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI). BACKGROUND: Increasingly, CABG and PCI are performed in older patients to treat multivessel disease, but their comparative effectiveness is uncertain. METHODS: Individual data from 7,812 patients randomized in 1 of 10 clinical trials of CABG or PCI were pooled. Age was analyzed as a continuous variable in the primary analysis and was divided into tertiles for descriptive purposes (≤56.2 years, 56.3 to 65.1 years, ≥65.2 years). The outcomes assessed were death, myocardial infarction and repeat revascularization over complete follow-up, and angina at 1 year. RESULTS: Older patients were more likely to have hypertension, diabetes, and 3-vessel disease compared with younger patients (p < 0.001 for trend). Over a median follow-up of 5.9 years, the effect of CABG versus PCI on mortality varied according to age (interaction p < 0.01), with adjusted CABG-to-PCI hazard ratios and 95% confidence intervals (CI) of 1.23 (95% CI: 0.95 to 1.59) in the youngest tertile; 0.89 (95% CI: 0.73 to 1.10) in the middle tertile; and 0.79 (95% CI: 0.67 to 0.94) in the oldest tertile. The CABG-to-PCI hazard ratio of less than 1 for patients 59 years of age and older. A similar interaction of age with treatment was present for the composite outcome of death or myocardial infarction. In contrast, patient age did not alter the comparative effectiveness of CABG and PCI on the outcomes of repeat revascularization or angina. CONCLUSIONS: Patient age modifies the comparative effectiveness of CABG and PCI on hard cardiac events, with CABG favored at older ages and PCI favored at younger ages

Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels

Background: In patients with refractory unstable angina, the platelet glycoprotein IIb/IIIa-receptor antibody abciximab reduces the incidence of cardiac events before and during coronary angioplasty. We investigated whether serum troponin T levels identify patients most likely to benefit from therapy with this drug. Methods: Among 1265 patients with unstable angina who were enrolled in the c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) trial, serum samples drawn at the time of randomization to abciximab or placebo were available from 890 patients; we used these samples for the determination of troponin T and creatine kinase MB levels. Patients with postinfarction angina were not included. Results: Serum troponin T levels at the time of study entry were elevated (above 0.1 ng per milliliter) in 275 patients (30.9 percent). Among patients receiving placebo, the risk of death or nonfatal myocardial infarction was related to troponin T levels. The six-month cumulative event rate was 23.9 percent among patients with elevated troponin T levels, as compared with 7.5 percent among patients without elevated troponin T levels (P<0.001). Among patients treated with abciximab, the respective six-month event rates were 9.5 percent for patients with elevated troponin T levels and 9.4 percent for those without elevated levels. As compared with placebo, the relative risk of death or nonfatal myocardial infarction associated with treatment with abciximab in patients with elevated troponin T levels was 0.32 (95 percent confidence interval, 0.14 to 0.62; P=0.002). The lower event rates in patients receiving abciximab were attributable to a reduction in the rate of myocardial infarction (odds ratio, 0.23; 95 percent confidence interval, 0.12 to 0.49; P<0.001). In patients without elevated troponin T levels, there was no benefit of treatment with respect to the relative risk of death or myocardial infarction at six months (odds ratio, 1.26; 95 percent confidence interval, 0.74 to 2.31; P=0.47). Conclusions: The serum troponin T level, which is considered to be a surrogate marker for thrombus formation, identifies a high-risk subgroup of patients with refractory unstable angina suitable for coronary angioplasty who will particularly benefit from antiplatelet treatment with abciximab

Prehospital ticagrelor in ST-segment elevation myocardial infarction

Background:The direct-acting platelet P2Y receptor antagonist ticagrelor can reduce the incidence of major adverse cardiovascular events when administered at hospital admission to patients with ST-segment elevation myocardial infarction (STEMI). Whether prehospital administration of ticagrelor can improve coronary reperfusion and the clinical outcome is unknown. Methods: We conducted an international, multicenter, randomized, double-blind study involving 1862 patients with ongoing STEMI of less than 6 hours' duration, comparing prehospital (in the ambulance) versus in-hospital (in the catheterization laboratory) treatment with ticagrelor. The coprimary end points were the proportion of patients who did not have a 70% or greater resolution of ST-segment elevation before percutaneous coronary intervention (PCI) and the proportion of patients who did not have Thrombolysis in Myocardial Infarction flow grade 3 in the infarct-related artery at initial angiography. Secondary end points included the rates of major adverse cardiovascular events and definite stent thrombosis at 30 days. Results: The median time from randomization to angiography was 48 minutes, and the median time difference between the two treatment strategies was 31 minutes. The two coprimary end points did not differ significantly between the prehospital and in-hospital groups. The absence of ST-segment elevation resolution of 70% or greater after PCI (a secondary end point) was reported for 42.5% and 47.5% of the patients, respectively. The rates of major adverse cardiovascular events did not differ significantly between the two study groups. The rates of definite stent thrombosis were lower in the prehospital group than in the in-hospital group (0% vs. 0.8% in the first 24 hours; 0.2% vs. 1.2% at 30 days). Rates of major bleeding events were low and virtually identical in the two groups, regardless of the bleeding definition use