Bernard Charbonnier

A Clinical Trial of Vena Caval Filters in the Prevention of Pulmonary Embolism in Patients with Proximal Deep-Vein Thrombosis

BACKGROUND The efficacy and safety of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis is still a matter of debate. METHODS Using a two-by-two factorial design, we randomly assigned 400 patients with proximal deep-vein thrombosis who were at risk for pulmonary embolism to receive a vena caval filter (200 patients) or no filter (200 patients), and to receive low-molecular-weight heparin (enoxaparin, 195 patients) or unfractionated heparin (205 patients). The rates of recurrent venous thromboembolism, death, and major bleeding were analyzed at day 12 and at two years. RESULTS At day 12, two patients assigned to receive filters (1.1 percent), as compared with nine patients assigned to receive no filters (4.8 percent), had had symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.22; 95 percent confidence interval, 0.05 to 0.90). At two years, 37 patients assigned to the filter group (20.8 percent), as compared with 21 patients assigned to the no-filter group (11.6 percent), had had recurrent deep-vein thrombosis (odds ratio, 1.87; 95 percent confidence interval, 1.10 to 3.20). There were no significant differences in mortality or the other outcomes. At day 12, three patients assigned to low-molecular-weight heparin (1.6 percent), as compared with eight patients assigned to unfractionated heparin (4.2 percent), had had symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.38; 95 percent confidence interval, 0.10 to 1.38). CONCLUSIONS In high-risk patients with proximal deep-vein thrombosis, the initial beneficial effect of vena caval filters for the prevention of pulmonary embolism was counterbalanced by an excess of recurrent deep-vein thrombosis, without any difference in mortality. Our data also confirmed that low-molecular-weight heparin was as effective and safe as unfractionated heparin for the prevention of pulmonary embolism.

A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism

BACKGROUND Low-molecular-weight heparin appears to be at least as effective and safe as standard, unfractionated heparin for the treatment of deep-vein thrombosis, but only limited data are available on the use of low-molecular-weight heparin to treat acute symptomatic pulmonary embolism. METHODS We randomly assigned 612 patients with symptomatic pulmonary embolism who did not require thrombolytic therapy or embolectomy to either subcutaneous low-molecular-weight heparin (tinzaparin) given once daily in a fixed dose or adjusted-dose, intravenous unfractionated heparin. Oral anticoagulant therapy was begun between the first and the third day and was given for at least three months. We compared the treatments at day 8 and day 90 with respect to a combined end point of recurrent thromboembolism, major bleeding, and death. RESULTS In the first eight days of treatment, 9 of 308 patients assigned to receive unfractionated heparin (2.9 percent) reached at least one of the end points, as compared,with 9 of 304 patients assigned to low-molecular-weight heparin (3.0 percent; absolute difference, 0.1 percentage point; 95 percent confidence interval, -2.7 to 2.6). By day 90, 22 patients assigned to unfractionated heparin (7.1 percent) and 18 patients assigned to low-molecular-weight heparin (5.9 percent) had reached at least one end point (P=0.54; absolute difference, 1.2 percentage points; 95 percent confidence interval, -2.7 to 5.1). The risk of major bleeding was similar in the two treatment groups throughout the study. CONCLUSIONS Under the conditions of this study, initial subcutaneous therapy with the low-molecular-weight heparin tinzaparin appeared to be as effective and safe as intravenous unfractionated heparin in patients with acute pulmonary embolism.

Diagnostic strategy for patients with suspected pulmonary embolism: a prospective multicentre outcome study

BACKGROUND We designed a prospective multicentre outcome study to evaluate a diagnostic strategy based on clinical probability, spiral CT, and venous compression ultrasonography of the legs in patients with suspected pulmonary embolism (PE). The main aim was to assess the safety of withholding anticoagulant treatment in patients with low or intermediate clinical probability of PE and negative findings on spiral CT and ultrasonography. METHODS 1041 consecutive inpatients and outpatients with suspected PE were included. Patients with negative spiral CT and ultrasonography and clinically assessed as having a low or intermediate clinical probability were left untreated. Those with high clinical probability underwent lung scanning, pulmonary angiography, or both. All patients were followed up for 3 months. FINDINGS PE was diagnosed in 360 (34.6%) patients; 55 had positive ultrasonography despite negative spiral CT. Of 601 patients with negative spiral CT and ultrasonography, 76 were clinically assessed as having a high probability of PE; lung scanning or angiography showed PE in four (5.3% [95% CI 1.5-13.1]). The remaining 525 patients were assessed as having low or intermediate clinical probability, and 507 of them were not treated. Of these patients, nine experienced venous thromboembolism during follow-up (1.8% [0.8-3.3]). The diagnostic strategy proved inconclusive in 95 (9.1%) patients, and pulmonary angiography was done in 74 (7.1%). INTERPRETATION Withholding of anticoagulant therapy is safe when the clinical probability of PE is assessed as low or intermediate and spiral CT and ultrasonography are negative.

Comparison of Thrombolysis Followed by Broad Use of Percutaneous Coronary Intervention With Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Acute Myocardial Infarction : Data From the French Registry on Acute ST-Elevation Myocardial Infarction (FAST-MI)

Background— Intravenous thrombolysis remains a widely used treatment for ST-elevation myocardial infarction; however, it carries a higher risk of reinfarction than primary PCI (PPCI). There are few data comparing PPCI with thrombolysis followed by routine angiography and PCI. The purpose of the present study was to assess contemporary outcomes in ST-elevation myocardial infarction patients, with specific emphasis on comparing a pharmacoinvasive strategy (thrombolysis followed by routine angiography) with PPCI. Methods and Results— This nationwide registry in France included 223 centers and 1714 patients over a 1-month period at the end of 2005, with 1-year follow-up. Sixty percent of the patients underwent reperfusion therapy, 33% with PPCI and 29% with intravenous thrombolysis (18% prehospital). At baseline, the Global Registry of Acute Coronary Events score was similar in thrombolysis and PPCI patients. Time to initiation of reperfusion therapy was significantly shorter in thrombolysis than in PPCI (median 130 versus 300 minutes). After thrombolysis, 96% of patients had coronary angiography, and 84% had subsequent PCI (58% within 24 hours). In-hospital mortality was 4.3% for thrombolysis and 5.0% for PPCI. In patients with thrombolysis, 30-day mortality was 9.2% when PCI was not used and 3.9% when PCI was subsequently performed (4.0% if PCI was performed in the same hospital and 3.3% if performed after transfer to another facility). One-year survival was 94% for thrombolysis and 92% for PPCI (P=0.31). After propensity score matching, 1-year survival was 94% and 93%, respectively. Conclusions— When used early after the onset of symptoms, a pharmacoinvasive strategy that combines thrombolysis with a liberal use of PCI yields early and 1-year survival rates that are comparable to those of PPCI.

Antithrombotic treatment and the risk of death and stroke in patients with atrial fibrillation and a CHADS2 score=1.

In patients with atrial fibrillation (AF) and an intermediate risk of stroke (CHADS2 score =1), available evidence from clinical trials is inconclusive and the present guidelines for the management of AF indicate that the choice between oral anticoagulant and aspirin in these patients is open. Our goal was to evaluate whether, in patients with AF and only one moderate risk factor for thromboembolism, treatment with an oral anticoagulant is appreciably more beneficial than treatment with an antiplatelet agent. Among 6,517 unselected patients with AF, 1,012 of them (15.5%) had a CHADS2 score of 1 and were liable to treatment with an antiplatelet agent or an anticoagulant. An oral anticoagulant was prescribed for 606 patients (59.9%) and an antiplatelet agent or no antithrombotic treatment for 406 (40.1%). During follow-up (median=793 days, interquartile range=1,332 days), 105 deaths (10.4%) and 19 strokes (1.9%) were recorded. The administration of an anticoagulant was associated with a lower rate of events (relative risk=0.42, 95% confidence interval 0.29-0.60, p<0.0001) than when no anticoagulant was prescribed. Results remained similar after adjustment for age and other confounding factors. In contrast, prescription of an antiplatelet agent was not associated with a lower risk of events. Factors independently associated with an increased risk of events were older age (p<0.0001), concomitant heart failure (p=0.0002), diabetes (p=0.0025), lack of prescription of an anticoagulant (p<0.0001) and permanent AF (p=0.04). Thus, prescription of an anticoagulant is independently associated with a decreased risk of death or stroke among patients with AF and a CHADS2 score =1.

Randomized, Double-Blind Study Comparing Saruplase With Streptokinase Therapy in Acute Myocardial Infarction: The COMPASS Equivalence Trial

Abstract Objectives. This study sought to demonstrate the equivalence of saruplase and streptokinase in terms of 30-day mortality. Background. The use of thrombolytic agents in the treatment of acute myocardial infarction is well established and has been shown to substantially reduce post-myocardial infarction mortality. Methods. Three thousand eighty-nine patients with symptoms compatible with those of acute myocardial infarction for Results. Death of any cause up to 30 days after randomization occurred in 88 (5.7%) of 1,542 patients randomized to receive saruplase and 104 (6.7%) of 1,547 patients randomized to receive streptokinase (odds ratio 0.84, p Conclusions. Saruplase is a clinically safe and effective thrombolytic medication. This profile ranks saruplase favorably among the currently available thrombolytic agents.

Improved outcome of cardiogenic shock at the acute stage of myocardial infarction: a report from the USIK 1995, USIC 2000, and FAST-MI French Nationwide Registries

AIM The historical evolution of incidence and outcome of cardiogenic shock (CS) in acute myocardial infarction (AMI) patients is debated. This study compared outcomes in AMI patients from 1995 to 2005, according to the presence of CS. METHOD AND RESULTS Three nationwide French registries were conducted 5 years apart, using a similar methodology in consecutive patients admitted over a 1-month period. All 7531 AMI patients presenting ≤48 h of symptom onset were included. The evolution of mortality was compared in the 486 patients with CS vs. those without CS. The incidence of CS tended to decrease over time (6.9% in 1995; 5.7% in 2005, P = 0.07). Thirty-day mortality was considerably higher in CS patients (60.9 vs. 5.2%). Over the 10-year period, mortality decreased for both patients with (70-51%, P = 0.003) and without CS (9-4%, P < 0.001). In CS patients, the use of percutaneous coronary intervention (PCI) increased from 20 to 50% (P < 0.001). Time period was an independent predictor of early mortality in CS patients (OR for death, 2005 vs. 1995 = 0.45; 95% CI: 0.27-0.75, P = 0.005), along with age, diabetes, and smoking status. When added to the multivariate model, PCI was associated with decreased mortality (OR = 0.38; 95% CI: 0.24-0.58, P < 0.001). In propensity-score-matched cohorts, CS patients with PCI had a significantly higher survival. CONCLUSIONS Cardiogenic shock remains a clinical concern, although early mortality has decreased. Improved survival is concomitant with a broader use of PCI and recommended medications at the acute stage. Beyond the acute stage, however, 1-year survival has remained unchanged.

Prognosis and Guideline-Adherent Antithrombotic Treatment in Patients With Atrial Fibrillation and Atrial Flutter: Implications of Undertreatment and Overtreatment in Real-life Clinical Practice; the Loire Valley Atrial Fibrillation Project

BACKGROUND In patients with atrial fibrillation (AF), adherence to guidelines for antithrombotic treatment is poorly followed, and undertreatment (or nonadherence with guidelines) is associated with a worse prognosis. The study objective was to evaluate whether this was also the case in a large contemporary series of unselected patients with AF in real-world clinical practice. METHODS All patients with AF or atrial flutter seen in our institution between 2000 and 2007 were identified in a database and followed up for mortality and stroke. Antithrombotic guideline adherence was assessed according to the 2006 American College of Cardiology/American Heart Association/European Society of Cardiology guidelines. RESULTS We reviewed outcomes in 3,646 consecutive patients with AF or atrial flutter (aged 71 ± 14 years; mean CHADS(2) [congestive heart failure, hypertension, aged ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score, 1.5 ± 1.1). Antithrombotic treatment was in agreement with the guidelines in 53% of patients, whereas 31% were classified as undertreated and 16% as overtreated. Among other parameters, nonpermanent AF and atrial flutter were independently associated with an increased risk of undertreatment. After a follow-up of 953 ± 767 days (median, 771 days; interquartile range, 1,286 days), guideline adherence was associated with a lower risk of adverse events (death from all causes or stroke) compared with undertreatment (relative risk, 0.47; 95% CI, 0.40-0.55; P < .0001). Overtreatment was associated with a lower risk of adverse events compared with the guideline-adherent population (relative risk, 0.40; 95% CI, 0.28-0.58; P < .0001). Factors independently associated with increased risk of mortality or stroke were antithrombotic undertreatment, older age, heart failure, renal failure, diabetes, male sex, and previous history of stroke. CONCLUSIONS Guideline nonadherence and undertreatment with antithrombotic agents in unselected real-world patients with AF or atrial flutter are independently associated with a high risk of stroke and mortality.

Comparison of Beta Blocker and Digoxin Alone and in Combination for Management of Patients With Atrial Fibrillation and Heart Failure

In patients with atrial fibrillation (AF) and heart failure (HF), beta blockers and digoxin reduce the ventricular rate, but controversy exists concerning how these drugs affect prognosis in this setting. This study compared the effects of beta blocker and digoxin on mortality in patients with both AF and HF. In a single-center institution, patients with AF and HF seen between January 2000 and January 2004 were identified and followed until September 2007. Of 1,269 consecutive patients with both AF and HF, 260 were treated with a beta blocker alone, 189 with beta blocker plus digoxin, 402 with digoxin alone, and 418 without beta blocker or digoxin (control group). During a follow-up of 881+/-859 days, 247 patients died. Compared with the control group, treatment with beta blocker was associated with a decreased mortality (relative risk=0.58, 95% confidence interval 0.40 to 0.85, p=0.005 for beta blocker alone and 0.59, 95% confidence interval 0.40 to 0.87, p=0.008 for beta blocker plus digoxin). By contrast, treatment with digoxin alone was not associated with a better survival (relative risk=0.97, 95% confidence interval 0.73 to 1.30, p=NS). Results remained significant after adjustment for potential confounders and similar when we considered, separately, HF with permanent or nonpermanent AF, presence or absence of coronary disease, and patients with decreased or preserved systolic function. In conclusion, in unselected patients with AF and HF, treatments with beta blocker alone or with beta blocker plus digoxin are associated with a similar decrease in the risk of death. Digoxin alone is associated with a worse survival chance, similar to that of patients without any rate control treatment.

Original ResearchCardiovascular DiseasePrognosis and Guideline-Adherent Antithrombotic Treatment in Patients With Atrial Fibrillation and Atrial Flutter: Implications of Undertreatment and Overtreatment in Real-life Clinical Practice; the Loire Valley Atrial Fibrillation Project

BACKGROUND In patients with atrial fibrillation (AF), adherence to guidelines for antithrombotic treatment is poorly followed, and undertreatment (or nonadherence with guidelines) is associated with a worse prognosis. The study objective was to evaluate whether this was also the case in a large contemporary series of unselected patients with AF in real-world clinical practice. METHODS All patients with AF or atrial flutter seen in our institution between 2000 and 2007 were identified in a database and followed up for mortality and stroke. Antithrombotic guideline adherence was assessed according to the 2006 American College of Cardiology/American Heart Association/European Society of Cardiology guidelines. RESULTS We reviewed outcomes in 3,646 consecutive patients with AF or atrial flutter (aged 71 ± 14 years; mean CHADS(2) [congestive heart failure, hypertension, aged ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score, 1.5 ± 1.1). Antithrombotic treatment was in agreement with the guidelines in 53% of patients, whereas 31% were classified as undertreated and 16% as overtreated. Among other parameters, nonpermanent AF and atrial flutter were independently associated with an increased risk of undertreatment. After a follow-up of 953 ± 767 days (median, 771 days; interquartile range, 1,286 days), guideline adherence was associated with a lower risk of adverse events (death from all causes or stroke) compared with undertreatment (relative risk, 0.47; 95% CI, 0.40-0.55; P < .0001). Overtreatment was associated with a lower risk of adverse events compared with the guideline-adherent population (relative risk, 0.40; 95% CI, 0.28-0.58; P < .0001). Factors independently associated with increased risk of mortality or stroke were antithrombotic undertreatment, older age, heart failure, renal failure, diabetes, male sex, and previous history of stroke. CONCLUSIONS Guideline nonadherence and undertreatment with antithrombotic agents in unselected real-world patients with AF or atrial flutter are independently associated with a high risk of stroke and mortality.