Interventional trials with anticoagulants in acutely ill medical patients: a methodological pitfall?

Abstract

Autopsy and retrospective studies [1][2][3][4] lead to believe that patients hospitalized for acute medical illness are at higher risk of deep venous thrombosis (DVT) and pulmonary embolism (PE) and that anticoagulant treatment was, therefore, necessary to prevent such vascular outcomes. Interventional trials consistently showed that prophylaxis with anticoagulants reduces the risk of composite endpoints of DVT, PE and DVT-related death in patients hospitalized for acute medical illness while no effect has been detected for total mortality [5]. These results prompted to recommend the use of anticoagulant prophylaxis in patients hospitalized for acute medical illness [6], but despite this, there is a large underuse of anticoagulant prophylaxis in the medical wards of hospitals [7,8].The scarce use of anticoagulants in acutely ill medical is almost evident in a multicenter clinical registry (The REPOSI study) performed by investigating patients hospitalized in Italian divisions of internal medicine [9].Thus, Marcucci et al.[9] included 1,121 acutely ill medical patients and followed them up during the hospital stay and until 3 months after hospital discharge. Patients included were very old, with a mean age of 82 years; males and females were equally distributed. Among 1,121 patients, 171 (15.2 %) were treated with thromboprophylaxis (TP) including low molecular weight heparin (n = 158), unfractionated heparin (n = 4) and fondaparinux (n = 9). Administration of anticoagulants was unrelated to the current guidelines of this setting as only 14.9 % of treated patients met the criteria of ACCP 2004 guidelines [10]. Among the putative risk factors considered, impaired global performance, as assessed by Barthel index [11], length of hospital stay and acute respiratory failure were independent predictors of TP during the hospitalization.Because the rate of patients treated with TP was low, the study offers an interesting chance to appreciate the rate of DVT in a relatively large population of acutely ill medical patients. Figure 1 depicts the rate of DVT in patients treated or not with TP. During the hospital stay among 950 untreated patients, DVT was diagnosed in 5 (0.5 %) while 1 (0.6 %) DVT was observed in the 171 treated patients; in the 3-month follow-up only three untreated and one treated patients experienced DVT. Taking into account the entire follow-up, 8 (0.8 %) untreated and 2 (1.1) treated patients experienced DVT. Pulmonary embolism was detected in two patients with DVT (one treated and one untreated) only after hospital discharge.We have recently reviewed the incidence of DVT in the interventional trials with anticoagulants performed in acutely ill medical patients [12].The rate of DVT was quite different if symptomatic or asymptomatic events were separately considered [12]. Thus, asymptomatic DVT was much more frequent compared to symptomatic ones with a large variation ranging as high as 28 % to as low as 2.3 % with an average of 4.7 % [12]. The rate of symptomatic DVT was much less with values from as hi...

New oral anticoagulants for the treatment of acute venous thromboembolism: are they safer than vitamin K antagonists? A meta-analysis of the interventional trials

“…VTE treatment with antithrombotic drugs such as vitamin K antagonists (VKA), unfractionated heparin (UFH), or low-molecular-weight heparin (LMWH) is recommended for most of these patients [3][4][5][6]. In the past, VKA represented the cornerstone of anticoagulant therapy.…”

Prophylaxis of venous thromboembolism in elderly patients with multi-morbidity: the REPOSI data

“…The accompanying editorial proposes a different reading of the REPOSI data based on the report by Violi et al [2] on the incidence of DVT in the interventional trials with anticoagulants performed in acutely ill medical patients. In the latter report, it has been documented that the rate of symptomatic DVT ranged in the interventional trials 1.5-0.8 % (average 0.99 %), that was almost twice as high as the incidence of symptomatic DVT in the REPOSI (0.5 %).…”

“…[2].Pharmacological thromboprophylaxis (TP) is known to reduce venous thromboembolism (VTE) in medical inpatients, but the criteria for risk-driven prescription, safety and impact on mortality are still debated. Risk assessment models assign a low weight to advanced age when it is the only risk factor for VTE.…”

“…Only 14.9 % of treated patients in the REPOSI met the requirements of those prescription guidelines. By employing as denominator the overall study population (15 % in the REPOSI and about 60 % in the IMPROVE) or only the patients who met the criteria for TP prescription according to the ACCP 2004 guidelines (30 % in the REPOSI, 40 % in ENDORSE, 33 % among IMPROVE patients from United States, 47 % among those from other countries), the REPOSI Investigators argue for different clinical setting (an elderly population, with probably a higher representation of frail patients in the REPOSI compared to those of the IMPROVE study and the ENDORSE registry), as potentially explaining the lower rate of TP in their study.The accompanying editorial proposes a different reading of the REPOSI data based on the report by Violi et al [2] on the incidence of DVT in the interventional trials with anticoagulants performed in acutely ill medical patients. In the latter report, it has been documented that the rate of symptomatic DVT ranged in the interventional trials 1.5-0.8 % (average 0.99 %), that was almost twice as high as the incidence of symptomatic DVT in the REPOSI (0.5 %).…”