Lack of effect of a low-molecular-weight heparin (nadroparin) on mortality in bedridden medical in-patients: A prospective randomised double-blind study

Service Médecine A, AP-HP, Hôpital Lariboisière, 2, rue Ambroise Paré, 75010, Paris, France.
European Journal of Clinical Pharmacology (Impact Factor: 2.97). 08/2005; 61(5-6):347-51. DOI: 10.1007/s00228-005-0944-3
Source: PubMed


Hospitalised medical patients are at significant risk of venous thromboembolic disease through fatal pulmonary embolism; low-molecular-weight heparins have been proved efficient in preventing deep venous thrombosis in surgical and medical patients, but their effect on mortality in bedridden medical patients remains unknown.
In a multi-centre, randomised, double-blind, placebo-controlled study, 2,474 consecutive patients aged over 40 years admitted to internal medicine departments in the last 24 h and unable to move alone were randomised to receive 0.3 ml nadroparin (7,500 anti-Xa units) or placebo for up to 21 days. The primary end-point was overall mortality at day 21.
There were no significant differences between the patients' characteristics. Overall mortality between the two groups was not statistically different [10.08% (124 of 1,230) versus 10.29% (128 of 1,244), respectively, in the nadroparin and in the placebo groups; relative risk reduction 0.02, CI (-0.27, +0.25), P=0.89]. An autopsy was performed in 123 of the 252 patients who died (49%). Pulmonary embolism was discovered at autopsy in 10 of 63 patients in the nadroparin group and in 17 of 60 in the placebo group [relative risk reduction 0.38, CI (-0.27, +0.70), P=0.13].
Nadroparin does not have a significant effect on mortality in bedridden medical patients, based on the study results. The study provides no data suggesting that low-molecular-weight heparins might reduce the incidence of thromboembolic in-patients hospitalised for an acute medical disease.

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    • "To date, there are not papers demonstrating mortality reduction with prophylactic treatment of VTE, even when overall mortality was specifically studied [21]. This is explained because, in clinical trials, the patients recruited have a low risk of death, as demonstrated by the low mortality rate in these studies [12] [13] [14]. "
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    ABSTRACT: Venous thromboembolism (VTE) includes deep vein thrombosis and pulmonary embolism. Although effective prophylaxis exists for medical patients, there is little information outside of clinical trials. We will analyze our experience in the prophylaxis of VTE with enoxaparin in hospitalized medical patients. We studied all of the patients ≥15 years admitted for emergency care to all of the medical departments of the hospital, except for the Hematology Department, between 1/April/1999 and 31/December/2005. The patients' age, sex, Charlson comorbidity index (CCI), whether they received prophylaxis with enoxaparin or not, dose, VTE, bleeding, thrombocytopenia, and mortality were analyzed. 40,349 patients were included, of which 55.87% were male, with an average age of 67.56, and an average CCI of 4.99. There were 19,834 patients who did not receive prophylaxis for which the rate of incidence of VTE was 0.61%, mortality 8.75%, bleeding 1.38%, and thrombocytopenia 0.04%. Prophylactic enoxaparin was administered to 20,515 patients, for which the rate of incidence of VTE was 0.44%, mortality 10.71%, bleeding 1.1%, and thrombocytopenia 0.04%. The adjusted Odds Ratio (OR) for VTE was 0.65 (95% confidence interval [95% CI] 0.49 to 0.87). The adjusted OR for mortality was 0.84 (95% CI 0.78 to 0.9). With the adjusted data, the number needed to treat (NNT) for VTE was 470.3 (95% CI 278.4 to 1413.3), and the NNT for mortality was 77.2 (95% CI 54.6 to 130.3). Thromboprophylaxis with enoxaparin in hospitalized medical patients is associated with a lower incidence of VTE and mortality, and is safe.
    Thrombosis Research 08/2011; 128(5):440-5. DOI:10.1016/j.thromres.2011.07.042 · 2.45 Impact Factor
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    • "In comparison to placebo, nadroparin failed to reduce the incidence of thromboembolic episodes, as well as the rate of mortality. The result reported by Mahe et al (2005) was in contrast with that of Gardlund (1996), who found a reduction in total mortality in patients hospitalized with an infectious disease. A meta-analysis of randomized trials addressed the value of prophylaxis with UFH or low molecular weight heparin (LMWH) in internal medicine (Mismetti et al, 2000). "
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    ABSTRACT: Acute venous thromboembolism (VTE) is a serious and potentially fatal disorder, which often complicates the course of hospitalized medical patients. This is particularly true for carriers of malignant diseases. While the introduction of thromboprophylactic measures has probably affected the occurrence of postoperative VTE, there is an increasing awareness of the importance of medical conditions in determining thromboembolic events. Simple and clinically relevant risk assessment models are available to facilitate VTE risk assessment in hospitalized medical patients. Their validation in prospective studies is in progress. Randomized controlled clinical trials have consistently documented the efficacy of heparins and fondaparinux for prevention of VTE in hospitalized medical patients with a minimal haemorrhagic risk. Recognition of the incidence and clinical importance of thrombosis will probably encourage more widespread use of antithrombotic prophylaxis in medical patients and especially in some particular types of malignancies.
    British Journal of Haematology 06/2008; 141(5):587-97. DOI:10.1111/j.1365-2141.2008.07089.x · 4.71 Impact Factor
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    • "Two double-blind randomized studies evaluated thromboprophylaxis without systematic assessment of asymptomatic DVT at the end of the treatment period (Bergmann and Caulin 1996; Lederle et al 2006). In the first study, nadroparin did not have a significant effect on mortality and the study provided no data suggesting that nadroparin may reduce the incidence of thromboembolic events in patients hospitalized for an acute medical disease (Bergmann and Caulin 1996; Mahe et al 2005). In the second study, the primary outcome was the total mortality at 90 days after randomization, but authors reported also the number of readmission due to objectively proven symptomatic venous thromboembolic events occurring within 90 days of randomization (Lederle et al 2006). "
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    ABSTRACT: Primary prophylaxis with the use of an effective and safe intervention appears the best approach of venous thromboembolism (VTE) management in medical elderly patients, the most affected by VTE. With increasing life expectancy, prevention of VTE, particularly in elderly patients, will arise as a major public health problem. Few well designed clinical trials evaluating thromboprophylaxis in medical settings were conducted in the specific population of geriatric patients. However, among the several pharmacological treatments evaluated, low molecular weight heparins enoxaparin 40 mg daily or dalteparin 5000 IU daily appeared effective and safe in the prevention of VTE in elderly patients. Despite available data, and recommendations for VTE prevention in medical patients, thromboprophylaxis is underused or misused in practice. Heterogeneity of clinical studies, selected populations, concern about bleeding, and lack of a clear clinical benefit are some of the reasons that could explain the gap between theory and practice. In this review, after a brief report of epidemiologic data and specificities of VTE in elderly patients, the authors discuss the available results of VTE primary prevention trials for elderly medical patients, the limitations of these data, and the challenges to improve the practice and to reduce the incidence of this frequent but preventable disease.
    Clinical Interventions in Aging 02/2008; 3(3):399-411. · 2.08 Impact Factor
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