Summary
Background
Recent clinical studies suggest that low-molecular-weight heparin (LMWH) could be an effective and safe alternative to unfractionated heparin (UFH) for patients with acute myocardial infarction (AMI).
Aims
To assess the impact of anticoagulant choice (LMWV vs UFH) on bleeding, the need for blood transfusion and 3-year clinical outcomes in AMI patients from the FAST-MI registry.
Methods
FAST-MI was a nationwide registry compiled in France over 1 month in 2005, which included consecutive AMI patients admitted to an intensive care unit less than 48 hours from symptom onset in 223 participating centres.
Results
A total of 2854 patients treated with heparins were included. The risks of major bleeding or transfusion (3.0% vs 7.0%) and in-hospital death (3.2% vs 9.2%) were lower with LMWH compared with UFH, a difference that persisted after multivariable adjustment (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.34–0.76 and OR 0.53, 95% CI 0.37–0.76, respectively). Three-year survival, and stroke and reinfarction-free survival risks were also higher with LMWH compared with UFH (adjusted hazard ratio [HR] 0.73, 95% CI 0.61–0.87 and HR 0.73, 95% CI 0.62–0.85, respectively). In two cohorts of patients matched on propensity score for receiving LMWH and with similar baseline characteristics (834 patients per group), major bleeding and transfusion rates were lower while the 3-year survival rate was significantly higher in patients receiving LMWH.
Conclusion
Our data suggest that the use of LMWH in AMI patients may have a better benefit/risk profile than UFH, in terms of bleeding, need for transfusion and long-term survival.
Résumé
Contexte
Les dernières études cliniques suggèrent que les héparines de bas poids moléculaires (HBPM) représentent une alternative sûre et efficace à l’héparine non fractionnée (HNF) pour la prise en charge des patients avec un infarctus du myocarde (IDM).
Objectifs
Évaluer l’impact des HBPM par rapport à l’HNF sur les saignements et le devenir des patients présentant un IDM à partir du registre FAST-MI.
Méthodes
FAST-MI est un registre national ayant inclus au cours d’un mois fin 2005 les patients ayant présenté un IDM au sein de 223 centres participants. Nous avons évalué l’impact des HBPM sur les saignements, les transfusions et la survie à trois ans.
Résultats
Au total, 2854 patients traités par héparine ont été inclus. Le risque de saignement majeur ou de transfusion (3,0 % vs 7,0 %, p < 0,001) et de décès intra-hospitalier (3,2 % vs 9,2 %, p < 0,001) étaient significativement moins élevés avec les HBPM qu’avec l’HNF ; résultats confirmés sur les analyses multivariées (OR 0,51, IC 95 % 0,34–0,76 et OR 0,53, IC 95 % 0,37–0,76, respectivement). L’utilisation des HBPM était associée de façon significative à une meilleur survie à trois ans et à la survenue de moins d’événements cardiovasculaires majeurs (décès, infarctus, accident vasculaire cérébral) comparée à l’HNF (HR 0,73, IC 95 % 0,61–0,87 et HR 0,73, IC 95 % 0,62–0,85, respectivement). Sur deux cohortes de patients appariés avec un score de propensité (834 patients par groupe), les patients traités par HBPM avaient significativement une meilleure survie à trois ans et moins de saignements majeurs et de transfusions.
Conclusion
Cette étude démontre que l’utilisation des HBPM chez les patients présentant un IDM est associée à une diminution des saignements, des transfusions et à une meilleure survie comparée à ceux traités par HNF.
Background
Several clinical studies have demonstrated that LMWHs (mainly enoxaparin) are an effective and safe alternative to UFH for the management of patients with ACS, with clinical benefit maintained long-term . A recent meta-analysis including more than 30,000 patients undergoing PCI showed that enoxaparin is superior to UFH in reducing mortality and bleeding outcomes, especially in patients undergoing PCI for STEMI . This meta-analysis confirms the results recently reported in the ATOLL randomized trial, in which the use of intravenous enoxaparin compared with UFH reduced clinical ischaemic outcomes without differences in bleeding and procedural success .
We aimed to determine, in a “real-world” setting, the impact of LMWH compared with UFH, in terms of bleeding events and long-term clinical outcomes in patients with AMI from the FAST-MI.
Methods
Patient population
The methods of the FAST-MI registry have been described in detail elsewhere . Briefly, the primary objective was to evaluate “real-life” MI management practices and to measure their impact on medium- and long-term prognosis in patients admitted to ICUs with AMI (within 48 hours). This registry resulted from a prospective multicentre (223 centres) study that included 3059 patients. Patients were recruited consecutively from ICUs over a period of 1 month (October 2005). Participation in the study was offered to all French institutions, university teaching hospitals, general and regional hospitals and private clinics with ICUs capable of receiving ACS emergencies.
Men and women aged over 18 years were included if they agreed to take part in the study and were admitted within 48 hours after symptom onset for an AMI characterized by the elevation of troponin or creatine phosphokinase-MB associated with at least one of the following elements: symptoms compatible with myocardial ischaemia; new pathological Q waves; and ST-T changes compatible with myocardial ischaemia.
Main exclusion criteria were: iatrogenic MI (defined as an MI occurring within 48 hours of a therapeutic procedure [bypass surgery, coronary angioplasty or any other medical or surgical intervention]); ACS diagnosis invalidated in favour of another diagnosis; unstable angina; and no increase in cardiac biomarkers.
Participation in the registry did not change the therapeutic approach of the cardiologist in any way. The registry was conducted in compliance with Good Clinical Practice, French Law and the French Data Protection Law. The protocol was reviewed by the Committee for the Protection of Human Subjects in Biomedical Research of Saint-Antoine Hospital and the FAST-MI registry data file was declared to the Commission Nationale Informatique et Liberté. Clinicaltrials.gov identifier: NCT00673036 .
Definition of the heparin groups
Two groups were formed according to the anticoagulant used during the first 48 hours: the LMWH group and the UFH group. Patients who received both anticoagulants were included in the LMWH group.
Definition of myocardial infarction and strategy
Although the diagnosis of AMI was independently made at each participating centre, to avoid heterogeneous criteria it was suggested that STEMI be defined as ST-segment elevation more than or equal to 1 mm or new bundle branch block seen in at least two contiguous leads at any location in the index or qualifying electrocardiogram, and that NSTEMI (non-Q wave MI) be defined as no ST-segment elevation seen in the index or qualifying electrocardiogram. Patients who died very early after admission and in whom cardiac markers were not measured were included if they had compatible signs or symptoms associated with typical ST changes.
Data collection and follow-up
Data on baseline characteristics (demographics, risk factors and medical history) were collected prospectively. All data were recorded on computerized case record forms by dedicated research technicians sent to each of the centres at least once a week. Follow-up data were collected through contact with the attending physicians, the patients or their families. If missing, vital status was assessed from the registry of the patient’s birthplace. Three-year follow-up was 97% complete. Bleeding was classified as major or minor according to the TIMI criteria . Regarding bleeding complications, four endpoints of interest were used: in-hospital major bleeding (defined as a fall in haemoglobin more than or equal to 5 g, a fall in haematocrit more than or equal to 15%, intracranial haemorrhage, retroperitoneal bleeding); minor bleeding (defined as fall in haemoglobin of 3–5 g/dL, a fall in haematocrit of 10–15%); use of any transfusion during the hospital stay; and 3-year survival.
Statistical analysis
Statistical analysis was performed using SPSS 20.0 software (IBM, Armonk, NY, USA). For quantitative variables, means, standard deviations and minimum and maximum values were calculated. In addition, medians with interquartile ranges were calculated for some of the variables. Discrete variables are presented as percentages. Comparisons were made with the Chi 2 test or Fisher’s exact test for discrete variables and with unpaired t tests, Wilcoxon sign-rank tests or one-way analyses of variance for continuous variables. Survival curves according to management methods were estimated using the Kaplan–Meier estimation and compared using a log-rank test. Multivariable analyses of predictors of in-hospital endpoints were made by using a backward stepwise multiple logistic regression method. Correlates of survival were determined using a multivariable backward stepwise Cox analysis. Variables listed in Table 1 were included in the models. In addition, a propensity score for receiving LMWH was calculated using multiple logistic regression and was used to build two cohorts of patients matched on the propensity score. Comparisons of events between the two propensity score-matched cohorts were made using similar methodology. For all analyses, P < 0.05 was considered significant.
| UFH ( n = 922) | LMWH ( n = 1932) | P | |
|---|---|---|---|
| Age (years) | 68.9 ± 14.4 | 65.5 ± 14.2 | <0.001 |
| Women | 310 (34) | 590 (31) | 0.05 |
| Body mass index (kg/m 2 ) | 26.9 ± 5.0 | 26.9 ± 4.5 | 0.98 |
| Hypertension | 561 (61) | 1055 (55) | 0.001 |
| Diabetes mellitus | 231 (25) | 424 (22) | 0.04 |
| Current smoking | 273 (30) | 600 (31) | 0.23 |
| Hyperlipidaemia a | 414 (45) | 940 (49) | 0.03 |
| Previous MI | 160 (17) | 318 (17) | 0.29 |
| Previous percutaneous intervention | 114 (12) | 253 (13) | 0.32 |
| Previous coronary artery bypass grafting | 61 (7) | 86 (5) | 0.01 |
| Previous heart failure | 62 (7) | 84 (4) | 0.005 |
| Previous stroke | 55 (6) | 83 (4) | 0.03 |
| Peripheral artery disease | 105 (11) | 149 (8) | 0.001 |
| Chronic renal insufficiency | 81 (9) | 62 (3) | <0.001 |
| STEMI | 551 (60) | 970 (50) | <0.001 |
| GRACE score | 158 ± 38 | 143 ± 35 | <0.001 |
| Left ventricular ejection fraction (%) | 45 ± 14 | 53 ± 13 | <0.001 |
| Atrial fibrillation on admission | 91 (10) | 118 (6) | <0.001 |
| Admission glycaemia (mg/dL) | 158 ± 78 | 146 ± 65 | <0.001 |
| Admission creatinine (mg/dL) | 117 ± 87 | 92 ± 30 | <0.001 |
| Left bundle branch block on admission | 46 (5) | 63 (3) | 0.02 |
| Anterior MI (% of STEMI) | 235 (43) | 366 (38) | 0.03 |
| Fibrinolytic treatment | 196 (21) | 265 (14) | <0.001 |
| Admission Killip class ≥ 2 | 253 (28) | 365 (19) | <0.001 |
| Antiplatelet agents before | 225 (25) | 470 (24) | 0.50 |
| Beta-blockers before | 219 (24) | 447 (23) | 0.38 |
| Statins before | 233 (25) | 515 (27) | 0.23 |
| Angiotensin-converting enzyme inhibitors before | 318 (35) | 609 (32) | 0.06 |
| Diuretics before | 262 (28) | 432 (22) | <0.001 |
| Calcium channel blockers before | 189 (21) | 333 (17) | 0.02 |
a Included patients with previously documented diagnosis of hypercholesterolaemia treated with diet or medication, or new diagnosis made during this hospitalization with elevated total cholesterol more than 160 mg/dL; did not include elevated triglycerides.
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