Christian Spaulding

Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis

BACKGROUND Whether the two drug-eluting stents approved by the US Food and Drug Administration-a sirolimus-eluting stent and a paclitaxel-eluting stent-are associated with increased risks of death, myocardial infarction, or stent thrombosis compared with bare-metal stents is uncertain. Our aim was to compare the safety and effectiveness of these stents. METHODS We searched relevant sources from inception to March, 2007, and contacted investigators and manufacturers to identify randomised controlled trials in patients with coronary artery disease that compared drug-eluting with bare-metal stents, or that compared sirolimus-eluting stents head-to-head with paclitaxel-eluting stents. Safety outcomes included mortality, myocardial infarction, and definite stent thrombosis; the effectiveness outcome was target lesion revascularisation. We included 38 trials (18,023 patients) with a follow-up of up to 4 years. Trialists and manufacturers provided additional data on clinical outcomes for 29 trials. We did a network meta-analysis with a mixed-treatment comparison method to combine direct within-trial comparisons between stents with indirect evidence from other trials while maintaining randomisation. FINDINGS Mortality was similar in the three groups: hazard ratios (HR) were 1.00 (95% credibility interval 0.82-1.25) for sirolimus-eluting versus bare-metal stents, 1.03 (0.84-1.22) for paclitaxel-eluting versus bare-metal stents, and 0.96 (0.83-1.24) for sirolimus-eluting versus paclitaxel-eluting stents. Sirolimus-eluting stents were associated with the lowest risk of myocardial infarction (HR 0.81, 95% credibility interval 0.66-0.97, p=0.030 vs bare-metal stents; 0.83, 0.71-1.00, p=0.045 vs paclitaxel-eluting stents). There were no significant differences in the risk of definite stent thrombosis (0 days to 4 years). However, the risk of late definite stent thrombosis (>30 days) was increased with paclitaxel-eluting stents (HR 2.11, 95% credibility interval 1.19-4.23, p=0.017 vs bare-metal stents; 1.85, 1.02-3.85, p=0.041 vs sirolimus-eluting stents). The reduction in target lesion revascularisation seen with drug-eluting stents compared with bare-metal stents was more pronounced with sirolimus-eluting stents than with paclitaxel-eluting stents (0.70, 0.56-0.84; p=0.0021). INTERPRETATION The risks of mortality associated with drug-eluting and bare-metal stents are similar. Sirolimus-eluting stents seem to be clinically better than bare-metal and paclitaxel-eluting stents.

Immediate Coronary Angiography in Survivors of Out-of-Hospital Cardiac Arrest

BACKGROUND The incidence of acute coronary-artery occlusion among patients with sudden cardiac arrest outside of the hospital is unknown, and the role of reperfusion therapy has not been determined. We therefore performed immediate coronary angiography and angioplasty when indicated in survivors of out-of-hospital cardiac arrest. METHODS Between September 1994 and August 1996, coronary angiography was performed in 84 consecutive patients between the ages of 30 and 75 years who had no obvious noncardiac cause of cardiac arrest. RESULTS Sixty of the 84 patients had clinically significant coronary disease on angiography, 40 of whom had coronary-artery occlusion (48 percent). Angioplasty was attempted in 37 patients and was technically successful in 28. Clinical and electrocardiographic findings, such as the occurrence of chest pain and the presence of ST-segment elevation, were poor predictors of acute coronary-artery occlusion. The in-hospital survival rate was 38 percent. Multivariate logistic-regression analysis revealed that successful angioplasty was an independent predictor of survival (odds ratio, 5.2; 95 percent confidence interval, 1.1 to 24.5; P=0.04). CONCLUSIONS Acute coronary-artery occlusion is frequent in survivors of out-of-hospital cardiac arrest and is predicted poorly by clinical and electrocardiographic findings. Accurate diagnosis by immediate coronary angiography can be followed in suitable candidates by coronary angioplasty, which seems to improve survival.

Successful Cardiopulmonary Resuscitation After Cardiac Arrest as a “Sepsis-Like” Syndrome

Background—We investigated the immunoinflammatory profile of patients successfully resuscitated after cardiac arrest, representing a model of whole-body ischemia/reperfusion syndrome. Methods and Results—Plasma cytokine, endotoxin, and ex vivo cytokine production in whole-blood assays was assessed in 61, 35, and 11 patients, respectively. On admission, high levels of plasma interleukin (IL)-6, IL-8, IL-10, and soluble tumor necrosis factor (TNF) receptor type II could discriminate between survivors and nonsurvivors. Among nonsurvivors, the initial need for a vasopressor agent was associated with higher levels of IL-1 receptor antagonist, IL-10, and IL-6 on day 1. Plasma endotoxin was detected in 46% of the analyzed patients within the 2 first days. Endotoxin-induced TNF and IL-6 productions were dramatically impaired in these patients compared with healthy control subjects, whereas an unaltered production was observed with heat-killed Staphylococcus aureus. In contrast, IL-1 receptor antagonist productions were enhanced in these patients compared with healthy control subjects. The productions of T-cell–derived IL-10 and interferon-&ggr; were also impaired in these patients. Finally, using in vitro plasma exchange between healthy control subjects and patients, we demonstrated that the endotoxin-dependent hyporeactivity was an intrinsic property of patients’ leukocytes and that an immunosuppressive activity was also present in their plasma. Conclusions—Altogether, the high levels of circulating cytokines, the presence of endotoxin in plasma, and the dysregulated production of cytokines found in these patients recall the immunological profile found in patients with sepsis.

Reversible myocardial dysfunction in survivors of out-of-hospital cardiac arrest ☆

OBJECTIVES The aim of the study was to assess the hemodynamic status of survivors of out-of-hospital cardiac arrest (OHCA). BACKGROUND The global prognosis after successfully resuscitated patients with OHCA remains poor. Clinical studies describing the hemodynamic status of survivors of OHCA and its impact on prognosis are lacking. METHODS Among 165 consecutive patients admitted after successful resuscitation from OHCA, 73 required invasive monitoring because of hemodynamic instability, defined as hypotension requiring vasoactive drugs, during the first 72 h. Clinical features and data from invasive monitoring were analyzed. RESULTS Hemodynamic instability occurred at a median time of 6.8 h (range 4.3 to 7.3) after OHCA. The initial cardiac index (CI) and filling pressures were low. Then, the CI rapidly increased 24 h after the onset of OHCA, independent of filling pressures and inotropic agents (2.05 [1.43 to 2.90] 8 h vs. 3.19 l/min per m(2) [2.67 to 4.20] 24 h after OHCA; p < 0.001). Despite a significant improvement in CI at 24 h, a superimposed vasodilation delayed the discontinuation of vasoactive drugs. No improvement in CI at 24 h was noted in 14 patients who subsequently died of multiorgan failure. Hemodynamic status was not predictive of the neurologic outcome. CONCLUSIONS In survivors of OHCA, hemodynamic instability requiring administration of vasoactive drugs is frequent and appears several hours after hospital admission. It is characterized by a low CI that is reversible in most cases within 24 h, suggesting post-resuscitation myocardial dysfunction. Early death by multiorgan failure is associated with a persistent low CI at 24 h.

Immediate Percutaneous Coronary Intervention Is Associated With Better Survival After Out-of-Hospital Cardiac Arrest Insights From the PROCAT (Parisian Region Out of Hospital Cardiac Arrest) Registry

Background— Acute coronary occlusion is the leading cause of cardiac arrest. Because of limited data, the indications and timing of coronary angiography and angioplasty in patients with out-of-hospital cardiac arrest are controversial. Using data from the Parisian Region Out of hospital Cardiac ArresT prospective registry, we performed an analysis to assess the effect of an invasive strategy on hospital survival. Methods and Results— Between January 2003 and December 2008, 714 patients with out-of-hospital cardiac arrest were referred to a tertiary center in Paris, France. In 435 patients with no obvious extracardiac cause of arrest, an immediate coronary angiogram was performed at admission followed, if indicated, by coronary angioplasty. At least 1 significant coronary artery lesion was found in 304 (70%) patients, in 128 (96%) of 134 patients with ST-segment elevation on the ECG performed after the return of spontaneous circulation, and in 176 (58%) of 301 patients without ST-segment elevation. The hospital survival rate was 40%. Multivariable analysis showed successful coronary angioplasty to be an independent predictive factor of survival, regardless of the postresuscitation ECG pattern (odds ratio, 2.06; 95% CI, 1.16 to 3.66). Conclusions— Successful immediate coronary angioplasty is associated with improved hospital survival in patients with or without ST-segment elevation. Therefore, our findings support the use of immediate coronary angiography in patients with out-of-hospital cardiac arrest with no obvious noncardiac cause of arrest regardless of the ECG pattern.Background—Acute coronary occlusion is the leading cause of cardiac arrest. Because of limited data, the indications and timing of coronary angiography and angioplasty in patients with out-of-hospital cardiac arrest are controversial. Using data from the Parisian Region Out of hospital Cardiac ArresT prospective registry, we performed an analysis to assess the effect of an invasive strategy on hospital survival. Methods and Results—Between January 2003 and December 2008, 714 patients with out-of-hospital cardiac arrest were referred to a tertiary center in Paris, France. In 435 patients with no obvious extracardiac cause of arrest, an immediate coronary angiogram was performed at admission followed, if indicated, by coronary angioplasty. At least 1 significant coronary artery lesion was found in 304 (70%) patients, in 128 (96%) of 134 patients with ST-segment elevation on the ECG performed after the return of spontaneous circulation, and in 176 (58%) of 301 patients without ST-segment elevation. The hospital survival rate was 40%. Multivariable analysis showed successful coronary angioplasty to be an independent predictive factor of survival, regardless of the postresuscitation ECG pattern (odds ratio, 2.06; 95% CI, 1.16 to 3.66). Conclusions—Successful immediate coronary angioplasty is associated with improved hospital survival in patients with or without ST-segment elevation. Therefore, our findings support the use of immediate coronary angiography in patients with out-of-hospital cardiac arrest with no obvious noncardiac cause of arrest regardless of the ECG pattern.

Randomized comparison of rescue angioplasty with conservative management of patients with early failure of thrombolysis for acute anterior myocardial infarction.

BACKGROUND When used in the setting of acute myocardial infarction, intravenous thrombolytic agents fail to achieve early infarct artery patency in 15% to 50% of patients. We tested the hypothesis that immediate balloon angioplasty applied to patients with failed early reperfusion would improve left ventricular function and clinical outcome at 30 days compared with conservative management alone. METHODS AND RESULTS One hundred fifty-one patients with first anterior wall infarction treated with any accepted intravenous thrombolytic regimen and angiographically demonstrated to have an occluded infarct vessel within 8 hours of chest pain onset were randomized to aspirin, heparin, and coronary vasodilators (conservative therapy) or to this therapy and balloon angioplasty supplemented by further thrombolytic therapy as needed. Left ventricular function was assessed using multiple-gated equilibrium radionuclide technique to determine ejection fraction, and adverse clinical outcome was assessed evaluating death, ventricular tachycardia, and class III or IV heart failure at 30 days. Seventy-three patients were randomized to conservative therapy and 78 to angioplasty. The two groups were well balanced for patient age (59 +/- 11 years), sex (82% were male), and time to randomization (4.5 +/- 1.9 hours). Angioplasty was technically successful in 72 of 78 randomized patients (92%). Two patients randomized to conservative therapy crossed over to angioplasty within 72 hours. Resting 30-day ejection fraction was 40 +/- 11% in the angioplasty group and 39 +/- 12% in the conservative group (P = .49), but ejection fraction with exercise was 43 +/- 15% and 38 +/- 13% for the angioplasty and conservatively treated groups, respectively (P = .04). Adverse clinical outcomes included death in 5% and 10% (P = .18), severe heart failure in 1% and 7% (P = .11), and either death or severe heart failure in 6% and 17% (P = .05) of the angioplasty and conservatively managed groups, respectively. CONCLUSIONS When applied to patients with first anterior infarction, rescue angioplasty appears to be useful in the prevention of death or severe heart failure, with improvement in exercise, but not resting, ejection fraction. This strategy deserves further study and highlights the potential advantage of early mechanical restoration of infarct vessel patency when thrombolytic therapy has failed.

Intracoronary Stent Implantation Without Ultrasound Guidance and With Replacement of Conventional Anticoagulation by Antiplatelet Therapy 30-Day Clinical Outcome of the French Multicenter Registry

BACKGROUND Stenting reduces both acute complications of coronary angioplasty and restenosis rates but increases subacute thrombosis rates and hemorrhagic complications when used with coumadin anticoagulation. METHODS AND RESULTS To simplify postcoronary stenting treatment and to reduce these drawbacks, we evaluated the 1-month outcome of a prospective registry of 2900 patients in whom successful coronary artery stenting was performed without coumadin anticoagulation. Patients received 100 mg/d aspirin and 250 mg/d ticlopidine for 1 month. Low-molecular-weight heparin (LMWH) treatment was progressively reduced in four consecutive stages, from 1-month treatment to none. Event-free outcome at 1 month was achieved in 2816 patients (97.1%). Major stent-related cardiac events were subacute closure in 51 patients (1.8%), including death in 12 (0.5%), acute myocardial infarction in 17 (0.6%), and coronary artery bypass graft surgery in 9 (0.3%). Stent thrombosis was more frequent with balloon size of < 3.0 mm (< or = 2.5 mm, 10%; 3.0 mm, 2.3%; > or = 3.5 mm, 1.0%; P < .001), bail-out situations (6.67% versus 1.38%, P < .001), and patients with unstable angina or acute myocardial infarction (2.2% versus 1.12%, P = .02). Bleeding complications that required transfusion, surgical repair, or both occurred in 55 patients (1.9%). Bleeding complications were related to female gender (4.0% versus 1.51%, P < .001), duration of LMWH treatment (3.83% in phase II/III versus 0.69% in phase IV/V, P < .001), sheath size (6F, 0.52%; 7F, 1.04%; > or = 8F, 4.23%; P < .001), bail-out situations (4.76% versus 1.67%, P < .01), and saphenous graft stenting (4.38% versus 1.75%, P = .04). CONCLUSIONS These results suggest that poststenting treatment by ticlopidine/aspirin is an effective alternative to coumadin anticoagulation, achieving low rates of subacute closure and bleeding complications. LMWH treatment does not improve subacute reocclusion rates but increases bleeding complications. Furthermore, as bleeding complications were independently related to sheath size, we suggest that stenting with 6F guiding catheters may prevent local complications. Furthermore, the ticlopidine/aspirin combination allows a low-cost stenting strategy without ultrasound assessment of stent deployment and permits short inhospital stay.

Postresuscitation disease after cardiac arrest: a sepsis-like syndrome?

Purpose of reviewDespite advances in cardiac arrest resuscitation, neurologic impairments and other organ dysfunctions cause considerable mortality and morbidity after restoration of spontaneous cardiac activity. The mechanisms underlying this postresuscitation disease probably involve a whole-body ischemia and reperfusion syndrome that triggers a systemic inflammatory response. Recent findingsPostresuscitation disease is characterized by high levels of circulating cytokines and adhesion molecules, the presence of plasma endotoxin, and dysregulated leukocyte production of cytokines: a profile similar to that seen in severe sepsis. Transient myocardial dysfunction can occur after resuscitation, mainly as a result of myocardial stunning. However, early successful angioplasty is independently associated with better outcomes after cardiac arrest associated with myocardial infarction. Coagulation abnormalities occur consistently after successful resuscitation, and their severity is associated with mortality. For example, plasma protein C and S activities after successful resuscitation are lower in nonsurvivors than in survivors. Low baseline cortisol levels may be associated with an increased risk of fatal early refractory shock after cardiac arrest, suggesting adrenal dysfunction in these patients. SummaryPostresuscitation abnormalities after cardiac arrest mimic the immunologic and coagulation disorders observed in severe sepsis. This suggests that therapeutic approaches used recently with success in severe sepsis should be investigated in patients successfully resuscitated after cardiac arrest.

Drug eluting and bare metal stents in people with and without diabetes: collaborative network meta-analysis

Objective To compare the effectiveness and safety of three types of stents (sirolimus eluting, paclitaxel eluting, and bare metal) in people with and without diabetes mellitus. Design Collaborative network meta-analysis. Data sources Electronic databases (Medline, Embase, the Cochrane Central Register of Controlled Trials), relevant websites, reference lists, conference abstracts, reviews, book chapters, and proceedings of advisory panels for the US Food and Drug Administration. Manufacturers and trialists provided additional data. Review methods Network meta-analysis with a mixed treatment comparison method to combine direct within trial comparisons between stents with indirect evidence from other trials while maintaining randomisation. Overall mortality was the primary safety end point, target lesion revascularisation the effectiveness end point. Results 35 trials in 3852 people with diabetes and 10 947 people without diabetes contributed to the analyses. Inconsistency of the network was substantial for overall mortality in people with diabetes and seemed to be related to the duration of dual antiplatelet therapy (P value for interaction 0.02). Restricting the analysis to trials with a duration of dual antiplatelet therapy of six months or more, inconsistency was reduced considerably and hazard ratios for overall mortality were near one for all comparisons in people with diabetes: sirolimus eluting stents compared with bare metal stents 0.88 (95% credibility interval 0.55 to 1.30), paclitaxel eluting stents compared with bare metal stents 0.91 (0.60 to 1.38), and sirolimus eluting stents compared with paclitaxel eluting stents 0.95 (0.63 to 1.43). In people without diabetes, hazard ratios were unaffected by the restriction. Both drug eluting stents were associated with a decrease in revascularisation rates compared with bare metal stents in people both with and without diabetes. Conclusion In trials that specified a duration of dual antiplatelet therapy of six months or more after stent implantation, drug eluting stents seemed safe and effective in people both with and without diabetes.

Immediate Percutaneous Coronary Intervention Is Associated With Better Survival After Out-of-Hospital Cardiac ArrestClinical Perspective

Background— Acute coronary occlusion is the leading cause of cardiac arrest. Because of limited data, the indications and timing of coronary angiography and angioplasty in patients with out-of-hospital cardiac arrest are controversial. Using data from the Parisian Region Out of hospital Cardiac ArresT prospective registry, we performed an analysis to assess the effect of an invasive strategy on hospital survival. Methods and Results— Between January 2003 and December 2008, 714 patients with out-of-hospital cardiac arrest were referred to a tertiary center in Paris, France. In 435 patients with no obvious extracardiac cause of arrest, an immediate coronary angiogram was performed at admission followed, if indicated, by coronary angioplasty. At least 1 significant coronary artery lesion was found in 304 (70%) patients, in 128 (96%) of 134 patients with ST-segment elevation on the ECG performed after the return of spontaneous circulation, and in 176 (58%) of 301 patients without ST-segment elevation. The hospital survival rate was 40%. Multivariable analysis showed successful coronary angioplasty to be an independent predictive factor of survival, regardless of the postresuscitation ECG pattern (odds ratio, 2.06; 95% CI, 1.16 to 3.66). Conclusions— Successful immediate coronary angioplasty is associated with improved hospital survival in patients with or without ST-segment elevation. Therefore, our findings support the use of immediate coronary angiography in patients with out-of-hospital cardiac arrest with no obvious noncardiac cause of arrest regardless of the ECG pattern.Background—Acute coronary occlusion is the leading cause of cardiac arrest. Because of limited data, the indications and timing of coronary angiography and angioplasty in patients with out-of-hospital cardiac arrest are controversial. Using data from the Parisian Region Out of hospital Cardiac ArresT prospective registry, we performed an analysis to assess the effect of an invasive strategy on hospital survival. Methods and Results—Between January 2003 and December 2008, 714 patients with out-of-hospital cardiac arrest were referred to a tertiary center in Paris, France. In 435 patients with no obvious extracardiac cause of arrest, an immediate coronary angiogram was performed at admission followed, if indicated, by coronary angioplasty. At least 1 significant coronary artery lesion was found in 304 (70%) patients, in 128 (96%) of 134 patients with ST-segment elevation on the ECG performed after the return of spontaneous circulation, and in 176 (58%) of 301 patients without ST-segment elevation. The hospital survival rate was 40%. Multivariable analysis showed successful coronary angioplasty to be an independent predictive factor of survival, regardless of the postresuscitation ECG pattern (odds ratio, 2.06; 95% CI, 1.16 to 3.66). Conclusions—Successful immediate coronary angioplasty is associated with improved hospital survival in patients with or without ST-segment elevation. Therefore, our findings support the use of immediate coronary angiography in patients with out-of-hospital cardiac arrest with no obvious noncardiac cause of arrest regardless of the ECG pattern.