Rémi Choussat

Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction.

BACKGROUND When administered in conjunction with primary coronary stenting for the treatment of acute myocardial infarction, a platelet glycoprotein IIb/IIIa inhibitor may provide additional clinical benefit, but data on this combination therapy are limited. METHODS We randomly assigned 300 patients with acute myocardial infarction in a double-blind fashion either to abciximab plus stenting (149 patients) or placebo plus stenting (151 patients) before they underwent coronary angiography. Clinical outcomes were evaluated 30 days and 6 months after the procedure. The angiographic patency of the infarct-related vessel and the left ventricular ejection fraction were evaluated at 24 hours and 6 months. RESULTS At 30 days, the primary end point--a composite of death, reinfarction, or urgent revascularization of the target vessel--had occurred in 6.0 percent of the patients in the abciximab group, as compared with 14.6 percent of those in the placebo group (P=0.01); at 6 months, the corresponding figures were 7.4 percent and 15.9 percent (P=0.02). The better clinical outcomes in the abciximab group were related to the greater frequency of grade 3 coronary flow (according to the classification of the Thrombolysis in Myocardial Infarction trial) in this group than in the placebo group before the procedure (16.8 percent vs. 5.4 percent, P=0.01), immediately afterward (95.1 percent vs. 86.7 percent, P=0.04), and six months afterward (94.3 percent vs. 82.8 percent, P=0.04). One major bleeding event occurred in the abciximab group (0.7 percent); none occurred in the placebo group. CONCLUSIONS As compared with placebo, early administration of abciximab in patients with acute myocardial infarction improves coronary patency before stenting, the success rate of the stenting procedure, the rate of coronary patency at six months, left ventricular function, and clinical outcomes.

Immediate vs Delayed Intervention for Acute Coronary Syndromes: A Randomized Clinical Trial

CONTEXT International guidelines recommend an early invasive strategy for patients with high-risk acute coronary syndromes without ST-segment elevation, but the optimal timing of intervention is uncertain. OBJECTIVE To determine whether immediate intervention on admission can result in a reduction of myocardial infarction compared with a delayed intervention. DESIGN, SETTING, AND PATIENTS The Angioplasty to Blunt the Rise of Troponin in Acute Coronary Syndromes Randomized for an Immediate or Delayed Intervention (ABOARD) study, a randomized clinical trial that assigned, from August 2006 through September 2008 at 13 centers in France, 352 patients with acute coronary syndromes without ST-segment elevation and a Thrombolysis in Myocardial Infarction (TIMI) score of 3 or more to receive intervention either immediately or on the next working day (between 8 and 60 hours after enrollment). MAIN OUTCOME MEASURES The primary end point was the peak troponin value during hospitalization; the key secondary end point was the composite of death, myocardial infarction, or urgent revascularization at 1-month follow-up. RESULTS Time from randomization to sheath insertion was 70 minutes with immediate intervention vs 21 hours with delayed intervention. The primary end point did not differ between the 2 strategies (median [interquartile range] troponin I value, 2.1 [0.3-7.1] ng/mL vs 1.7 [0.3-7.2] ng/mL in the immediate and delayed intervention groups, respectively; P = .70). The key secondary end point was observed in 13.7% (95% confidence interval, 8.6%-18.8%) of the group assigned to receive immediate intervention and 10.2% (95% confidence interval, 5.7%-14.6%) of the group assigned to receive delayed intervention (P = .31). The other end points, as well as major bleeding, did not differ between the 2 strategies. CONCLUSION In patients with acute coronary syndromes without ST-segment elevation, a strategy of immediate intervention compared with a strategy of intervention deferred to the next working day (mean, 21 hours) did not result in a difference in myocardial infarction as defined by peak troponin level. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00442949.

Unprotected left main coronary artery stenting: correlates of midterm survival and impact of patient selection.

BACKGROUND The study served to present the in-hospital and six-month clinical outcome and also the long-term survival data of a consecutive series of patients undergoing stenting for unprotected left main coronary artery (LMCA) disease. METHODS Revascularization with coronary bypass surgery has been generally recommended for treatment of left main coronary stenosis. Improvements in angioplasty and coronary stent techniques and equipment may result in the wider applicability of a percutaneous approach. A total of 92 consecutive patients underwent unprotected LMCA stenting between March 1994 and December 1998. For the initial 39 patients (group I) angioplasty was performed only when surgical revascularization was contraindicated. The remaining 53 patients (group II) also included patients in whom surgery was feasible. Patients were followed for 7.3 +/- 5.8 months (median 239 days; range 49 to 1,477 days). RESULTS Compared to group I, group II patients had higher left ventricular ejection fraction (60 +/- 12% vs. 51 +/- 16%, p < 0.01), less severe LMCA stenosis (68 +/- 12% vs. 80 +/- 10%, p < 0.001), lower surgical risk score (13 +/- 7 vs. 20 +/- 7, p < 0.001), and had angioplasty more often performed via the radial approach (88% vs. 23%, p < 0.001) with smaller guiding catheters (6F: 49% vs. 15%; 8F: 2% vs. 77%, p < 0.001). The procedural success rate was 100%. In-hospital mortality was 4% (4 deaths, 3 cardiac). During follow-up there were six deaths, 13 patients required repeat percutaneous transluminal coronary angioplasty (4 LMCA), and two required coronary artery bypass graft surgery. Estimated survival (+/- SEE) was 89 +/- 6.3% at 500 days and 85 +/- 12% at 1,000 days post-stenting. Overall mortality was 3.8% in group II and 20.5% in group I (p < 0.02). CONCLUSIONS Coronary stenting can be performed safely in high-risk individuals with acceptable intermediate-term outcome. It may be feasible to broaden the application of this technique in selected patients needing revascularization for left main coronary disease.

Effects of various anticoagulant treatments on von Willebrand factor release in unstable angina.

OBJECTIVES We tested the hypothesis that different anticoagulant treatments may produce different platelet effects and von Willebrand factor (vWf) release in unstable angina. BACKGROUND The early increase of vWf has been reported to be a risk factor for adverse outcome in unstable angina. Anticoagulant drugs play a key role in stabilization of unstable angina, but they may not have the same efficacy and the same effects on acute vWf release. METHODS We studied 154 patients enrolled in several clinical trials testing four different anticoagulant treatments in unstable angina or non-Q-wave myocardial infarction. Patients were treated during at least 48 h by either intravenous unfractionated heparin, one of two different low molecular weight heparins (enoxaparin or dalteparin) or the direct thrombin inhibitor PEG-hirudin. All patients received aspirin but no Ib/IIIa inhibitors. RESULTS The release of vWf over the first 48 h (delta vWf) did not relate to the baseline clinical characteristics. At 30 days of follow-up, delta vWf was sevenfold higher in patients with an end point (death, myocardial infarction, revascularization) than in patients free of events (+53 +/-7% vs. +7 +/-14%, p = 0.004). The same trend was present for each component of the composite end point with the highest levels for one-month mortality (+87 +/- 32% vs. +26 +/- 8%, p = 0.09). The vWf values did not increase over 48 h in patients receiving either enoxaparin or PEG-hirudin (+10 +/- 9% and -5 +/- 20%, respectively). A serious rise ofvWf was measured in unfractionated heparin-treated patients (+87 +/- 11%), which differed significantly from the enoxaparin group (p = 0.0006) and PEG-hirudin group (p < 0.0001). In dalteparin-treated patients, delta vWf was elevated (+48 +/- 8%) and did not differ from the unfractionated heparin group (NS). CONCLUSIONS We confirm that, in unstable angina patients, a rise of vWf over the first 48 h is associated with an impaired outcome at 30 days. Moreover, the four different anticoagulant treatments tested here do not provide the same protection with regards to vWf release, which may have important prognostic implications and explain different results observed in recent clinical trials.

In-stent restenosis: long-term outcome and predictors of subsequent target lesion revascularization after repeat balloon angioplasty

OBJECTIVES We sought to evaluate the long-term clinical outcome of patients undergoing successful balloon angioplasty for in-stent restenosis, and to determine correlates of the need for subsequent target lesion revascularization (TLR). BACKGROUND In-stent restenosis can be safely treated by repeat percutaneous intervention. Reported subsequent TLR rates have varied from 20% to 80% and seem related to the type of restenotic lesion. METHODS The study population comprised 234 patients with follow-up data who were successfully treated with repeat balloon angioplasty for in-stent restenosis in 257 lesions between May 1995 and January 1998 at our institution. RESULTS Clinical follow-up was available at 459 (286 to 693) days after the repeat procedure. Event-free survival was 78.5% and 74.6% at 12 and 24 months, respectively. Recurrent events occurred in 58 patients (24.8%), including 6 deaths (2.6%), 4 myocardial infarction (1.7%) and repeat target vessel revascularization in 50 patients (21.4%). Independent predictors of repeat TLR were time to in-stent restenosis <90 days (Hazard ratio 4.67, p < 0.001), minimal luminal diameter after repeat procedure (Hazard ratio 0.38, p = 0.034) and the angiographic pattern of in-stent restenosis (Hazard ratio 1.65, p = 0.036). CONCLUSIONS Balloon angioplasty is an effective means of treating in-stent restenosis. The long-term results are acceptable particularly for focal restenotic lesions. Further restenosis is more common in patients with early initial recurrence, more proliferative lesions and a poorer angiographic result from repeat angioplasty.

Effects of prostacyclin on the pulmonary vascular tone and cardiac contractility of patients with pulmonary hypertension secondary to end-stage heart failure.

Long-term administration of prostacyclin (PGI2) improves the hemodynamic state, symptoms, and survival in patients with primary pulmonary hypertension, but it increases mortality in patients with heart failure despite obvious hemodynamic benefits when it is given acutely. We evaluated the mechanisms of action of PGI2 in patients with heart failure and secondary pulmonary hypertension. Nineteen patients with end-stage heart failure and pulmonary hypertension, all candidates for heart transplantation, underwent right- and left sided cardiac catheterization with micromanometer-tipped catheters and were tested for PGI2 at incremental doses. PGI2 infusion significantly improved pulmonary hemodynamics with a 47% reduction in pulmonary vascular resistance (p=0.0003) and a doubling of pulmonary artery compliance (p <0.0001), reflecting improvement in pulmonary vascular tone. The dose of PGI2 necessary to reach this hemodynamic effect correlated significantly to the baseline severity of pulmonary artery compliance (r=0.54, p=0.01). Furthermore, PGI2 produced a significant positive inotropic effect (contractile element maximum velocity increased from 1.10+/-0.09 to 1.33+/-0.13 circ/s, p <0.009). The hemodynamic effects of PGI2 infusion were independent of the plasma and urinary levels of endogen prostaglandins. Thus, PGI2 at therapeutic doses exerts a positive inotropic effect in patients with heart failure, which may explain the increased mortality rate observed with the long-term use of PGI2 in this type of patient. The spectacular acute benefits on right ventricular afterload, however, may be useful in unstable patients with heart failure and secondary pulmonary hypertension or in transplanted patients with acute right ventricular failure of the donor heart.

Effects of Abciximab on the Architecture of Platelet-Rich Clots in Patients With Acute Myocardial Infarction Undergoing Primary Coronary Intervention

Background—Abciximab plus aspirin improves the TIMI 3 flow rate of the infarct-related artery in patients treated with either percutaneous coronary intervention or thrombolysis. The present study investigated whether the reperfusion efficacy of abciximab relates to modifications of clot architecture in patients admitted for acute myocardial infarction (AMI). Methods and Results—A total of 23 AMI patients in the Abciximab before Direct angioplasty and stenting in Myocardial Infarction Regarding Acute and Long term follow-up (ADMIRAL) trial received, in a double-blind fashion, either abciximab (n=13) or placebo (n=10) before primary stenting. Viscoelastic (G′ in dyne/cm2) and morphological (mean platelet aggregate surface area [SAG] in &mgr;m2) indexes of ex vivo platelet-rich clots (PRC) were assessed in a double-blind fashion before and after the bolus administration of abciximab or placebo. G′ and SAG reflect the mechanical and morphological impact of activated platelets on the PRC fibrin network, respectively. Abciximab administration reduced G′ by 63% (P =0.0001) and SAG by 65% (P =0.0007), and no effect was seen in the placebo group. These abciximab-related changes increased fibrin exposure as a consequence of the platelet-aggregate surface reduction and may have improved endogenous fibrinolysis. These effects were identified in all patients, independent of previous heparin administration. Conclusions—Abciximab dramatically reduces platelet aggregate size and increases the fibrin accessibility of ex vivo PRC in AMI patients. These modifications could participate in the better coronary artery patency observed with abciximab.

Low-molecular-weight heparin vs. unfractionated heparin in percutaneous coronary intervention: a combined analysis

This meta‐analysis assessed the rates of the efficacy and safety endpoints with intravenous low‐molecular‐weight heparin (LMWH) compared with unfractionated heparin (UFH) in patients undergoing percutaneous coronary intervention (PCI). Subcutaneous LMWH has compared favorably with UFH, but limited experience exists with intravenous LMWH for immediate anticoagulation in PCI. The meta‐analysis included data from eight randomized trials in which patients received LMWH (n = 1,037) or UFH (n = 978) during PCI. Seven additional nonrandomized studies/registries were analyzed to assess the efficacy and safety of LMWH during PCI. Efficacy endpoints were ischemic events (usually a composite of death, myocardial infarction, and urgent revascularization) and the safety endpoint was bleeding (major, minor, or all bleeding). In the randomized studies, LMWH was comparable with UFH in terms of efficacy (6.2% vs. 7.5%) and major bleeding (0.9% vs. 1.8%). The analysis of pooled data, randomized or not, suggests potential improved efficacy (5.8% vs. 7.6%) and reduced major bleeding (0.6% vs. 1.8%) with LMWH (n = 3,787) compared with UFH (n = 978). During PCI, intravenous LMWH without coagulation monitoring has the potential to be at least as safe and efficacious as intravenous UFH. Further studies of LMWHs in PCI are therefore required.

Heparin or enoxaparin anticoagulation for primary percutaneous coronary intervention

Objectives: The aim of this study was to compare efficacy and safety outcomes among patients receiving enoxaparin or unfractionated heparin (UFH) while undergoing percutaneous coronary intervention (PCI) for ST‐segment elevation myocardial infarction (STEMI). Background: Primary PCI (pPCI) for ST elevation has traditionally been supported by UFH. The low molecular weight heparin enoxaparin may provide better outcomes when used for pPCI. Methods: Consecutive eligible patients (580) undergoing pPCI enrolled in the prospective electronic Pitié‐Salpêtrière registry of ischemic coronary syndromes (e‐PARIS) registry were grouped according to whether they received UFH or enoxaparin as the sole anticoagulant. Logistic regression modeling, propensity‐weighted adjustment, and sensitivity analyses were used to evaluate efficacy and safety endpoints for enoxaparin vs. UFH. Results: Enoxaparin was administered to 346 patients and UFH to 234 without ACT or anti‐Xa guided dose adjustment. PCI was performed through the radial artery in 90%, with frequent (75%) use of GPIIb/IIIa antagonists. Patients receiving enoxaparin were more likely to be therapeutically anticoagulated during the procedure (68% vs. 50%, P < 0.0001) and were less likely to experience death or recurrent myocardial infarction (MI) in hospital (adjusted OR 0.28 95% CI (0.12–0.68) or by 30 days (adjusted OR 0.35 95% CI 0.16–0.81). All cause mortality was also reduced in hospital (adjusted OR 0.32, 95% CI (0.12–0.85) and to 30 days (adjusted OR 0.40 95% CI 0.17–0.99). Other ischemic endpoints were similarly reduced with enoxaparin. Thrombolysis in myocardial infarction (TIMI) major bleeding events were numerically fewer among patients receiving enoxaparin (1.2% vs. 2.6%, P = 0.2). Conclusions: In patients with STEMI presenting for PCI, enoxaparin was associated with a reduction in all ischemic complications, more frequent therapeutic anticoagulation, and no increase in major bleeding when compared against unfractionated heparin.

Long-term clinical outcome after endoluminal reconstruction of diffusely degenerated saphenous vein grafts with less-shortening wallstents.

OBJECTIVES This study was designed to evaluate the immediate and long-term clinical results of patients undergoing endoluminal reconstruction in diffusely degenerated saphenous vein grafts (SVGs) with elective implantation of one or more less-shortening Wallstents. BACKGROUND The optimal treatment strategy for patients with diffusely degenerated SVGs is controversial. Endoluminal reconstruction by stent implantation is one proposed strategy; however, there are few data regarding long-term clinical outcome. METHODS Between May 1995 and September 1998, 6,534 consecutive patients underwent angioplasty in our institution, including 440 who were treated for SVG lesions. Of these, 126 (115 men, 11 women, median age 69.5 years, range: 33-86 years) with old SVGs (mean age: 13+/-5 years) diffusely degenerated stenosed or occluded (mean lesion length: 27+/-12 mm) were treated electively with implantation of one or multiple (total 197) less-shortening Wallstents. RESULTS Before discharge, 13 patients (10.3%) sustained at least one major cardiovascular event, including 4 deaths (3.2%), 11 myocardial infarctions (MI) (8.7%), and 3 repeat revascularizations (target vessel = 1, nontarget vessel = 2, 2.4%). Surviving patients were followed for 22+/-11 months: 13 patients (11.1%) died, 11 (9.4%) sustained an MI, 37 underwent angioplasty (31.6%), and 4 (3.4%) underwent bypass surgery. The estimated three-year event-free survival rates (freedom from death, and freedom from death/MI/target vessel revascularization) were (mean +/- SE) 81.1+/-7.8% and 43.2+/-18.5%, respectively. CONCLUSIONS The long-term clinical outcome of patients undergoing endoluminal reconstruction in diffusely degenerated SVG is relatively poor, mainly because of a high incidence of death or MI and the frequent need for repeat angioplasty. It is unlikely that percutaneous intervention alone will provide a satisfactory or definitive solution for these patients.