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Use of rivaroxaban in an elderly patient with intermediate-low early mortality risk due to pulmonary embolism: a case report
© Menichetti et al. 2015
Received: 12 June 2015
Accepted: 5 November 2015
Published: 26 November 2015
Pulmonary embolism remains one of the leading causes of cardiovascular mortality. The standard treatment for pulmonary embolism is anticoagulant therapy using low molecular weight heparin, fondaparinux and a vitamin K antagonist, but a recent clinical trial showed that rivaroxaban, an oral factor Xa inhibitor, was as effective as standard therapy for the initial and long-term treatment of pulmonary embolism and had less bleeding complications.
The present report describes the case of an 80-year-old white man with an intermediate to low early mortality risk of pulmonary embolism. He was successfully treated with rivaroxaban (administered orally as monotherapy), demonstrating rapid benefit without any adverse events.
Rivaroxaban, particularly in the acute phase of pulmonary embolism, may be considered an effective and safe therapeutic choice even in elderly patients, a population less represented in clinical trials.
The elements that constitute venous thromboembolism (VTE) are deep vein thrombosis (DVT) and pulmonary embolism (PE). VTE is the third most frequent cardiovascular disease, with an overall annual prevalence of 100 to 200 cases per 100,000 inhabitants [1, 2].
PE is defined as the blockage of the main pulmonary artery or its branches by substances that have travelled through the bloodstream, most commonly resulting from DVT. It is difficult to assess its epidemiology because it can remain asymptomatic for a long period of time, or its diagnosis may be an incidental finding . PE is responsible for the mortality, morbidity, and hospitalization in a significant number of patients in Europe . The main clinical characteristics of patients with suspected PE are dyspnea, chest pain, fever, hemoptysis, syncope and signs of DVT. In some cases, the first presentation of PE may be sudden death [3, 4]. Diagnosis is based on clinical findings in combination with laboratory tests (such as the D-dimer test) and imaging studies, usually a computed tomographic (CT) pulmonary angiography.
The standard therapy for patients with acute PE is low molecular weight heparin (LMWH), fondaparinux overlapped with and then followed by vitamin K antagonists (VKA); the VKAs are dose-adjusted to keep an international normalized ratio (INR) between 2.0 and 3.0. This regimen is effective but complex. In the EINSTEIN PE clinical trial rivaroxaban, a direct and reversible inhibitor of factor Xa that can be administered orally, demonstrated non-inferiority versus standard treatment in terms of primary outcome (recurrent VTE) in patients with symptomatic PE with objective confirmation, with or without symptomatic DVT. Furthermore, major bleeding was reduced in the rivaroxaban group compared to the standard therapy group .
Based on these promising results, we decided to treat an elderly patient with PE without hemodynamic compromise with rivaroxaban.
An 80-year-old white man was admitted to our emergency department (DEA) presenting with dyspnea; this symptom appeared 2 weeks before and worsened a few days prior to hospital admission. He did not present other symptoms or signs; in particular he did not report thoracic pain or unilateral extremity swelling. He had no previous episodes of VTE, major trauma, immobilization or any other risk factors, such as obesity, cancer or family history suggestive of inherited thrombophilia.
Laboratory findings on admission revealed a high serum D-dimer level (6987 ng/L), elevated high-sensitivity cardiac troponin concentration (137 ng/l) and increased serum level of pro-B-type natriuretic peptide (pro-BNP; 6166 ng/L), while renal (creatinine 1.53 mg/dl and glomerular filtration rate 43 ml/minute/1.73m2) and liver function were normal. The focused assessment with sonography for trauma (FAST) scan performed in DEA showed a moderate right ventricular (RV) dilation and hypokinesia with flattening of his interventricular septum and dilated inferior vena cava.
Simplified Pulmonary Embolism Severity Index score
Simplified Pulmonary Embolism Severity Index score
Age >80 years
History of cancer
Chronic cardiopulmonary disease*
Pulse ≥110 beats/minute
SBP <100 mmHg
Arterial oxyhemoglobin saturation level <90 %
Laboratory findings on admission (27 January 2014) and the next 3 days
Troponin T >50 ng/L
Pro-BNP <1800 ng/L
D-dimer <100 ng/L
Five days after starting therapy, we performed another echocardiography showing a normalized RV function: ejection fraction (EF) of 55 %, systolic pulmonary artery pressure (PAPs) of 30 mmHg, and tricuspid annular plane systolic excursion (TAPSE) of 26 mm.
PE is a potentially life-threatening medical emergency that requires urgent intervention. Occlusion of the pulmonary arterial bed can lead to a potentially reversible RV failure. The diagnosis of PE can be missed because of nonspecific clinical presentation. However, early diagnosis is fundamental, since immediate treatment is highly effective [1, 2].
There is an extensive range of patient-related and setting-related risk factors. PE can be ‘provoked’ in the presence of temporary or reversible risk factors (such as surgery, trauma and immobilization) and ‘unprovoked’ in their absence. PE may also occur in the absence of any known risk factor. Patients older than 40 years are at increased risk compared with younger patients and the risk approximately doubles with each subsequent decade .
In the present case we describe a patient who presented with dyspnea without any other symptom or risk factor for PE, except that of advanced age. A physical examination and investigations did not support the possible existence of any other cause of dyspnea and led to the suspicion of PE. According to current guidelines , given the hemodynamic stability and low PE clinical probability of the patient, we first assessed serum D-dimer levels and then we performed a CT pulmonary angiography. This imaging test supported the diagnosis of bilateral PE. Echocardiography showed a RV dysfunction with significant overload. The combination of clinical findings with imaging and laboratory tests allows stratification of the early mortality risk (understood as in-hospital or 30-day mortality). Our patient, having a sPESI of 0 but both positivity for signs of RV dysfunction and cardiac laboratory biomarkers, was classified as having an intermediate to low early mortality risk.
The sPESI score [7–9] is used by many emergency physicians and acute care internists to stratify the risk of patients with PE in order to determine the most appropriate management approach, including suitability for out-patient care. The score predicts 30-day mortality following PE based on factors such as age, blood pressure, heart rate, oxygen saturation and the presence of chronic cardiopulmonary disease or cancer.
For half a century, the standard therapy for PE has been the administration of parental anticoagulant overlapped with and then followed by a VKA . This regimen has been shown to be extremely effective but with several limitations: requirement for laboratory monitoring and regular dose adjustments, need for injection, narrow therapeutic window and interactions with food and other drugs. Novel oral anticoagulants overcome the limitations of this standard therapy.
Rivaroxaban is a direct and reversible inhibitor of factor Xa that can be administered orally [11, 12]. It offers a simple single-drug approach for initial intensive treatment with a high dose (15 mg twice a day) administered for 3 weeks followed by administration of a standard dose (20 mg once a day). Findings from the recent EINSTEIN PE trial indicate that rivaroxaban was non-inferior compared to standard therapy (2.1 % events in the rivaroxaban group versus 1.8 % in the standard therapy group; hazard ratio 1.12; 95 % confidence interval, CI, 0.75 to 1.68) and no increase in adverse events when compared with standard treatment (LMWH with VKA) . In particular, the safety profile was attractive because major bleeding was observed in 26 patients (1.1 %) in the rivaroxaban group and 52 patients (2.2 %) in the standard therapy group (hazard ratio 0.49; 95 % CI 0.31 to 0.79; P=0.003).
This paper presents some similarities with respect to this clinical trial but the age of our patient was not comparable (80 years versus a mean age of 57.9±7.3 years in EINSTEIN PE). Despite the older age of our patient, we felt confident in using rivaroxaban instead of standard therapy. In fact, treatment with rivaroxaban led to rapid improvement and normalization (after 3 days) of PE-related early mortality risk markers.
In summary, this is the first case report showing that initial intensive treatment with rivaroxaban in an elderly patient resulted in a rapid clinical improvement and normalization of PE-related early mortality risk parameters. Furthermore, no adverse events were noted. This case suggests that rivaroxaban can be considered an effective alternative to standard therapy with LMWH and oral VKA for elderly patients with a hemodynamically stable PE.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
The authors would like to thank Dr Colin Gerard Egan and Dr Clara Ricci (Primula Multimedia SRL, Pisa, Italy) who provided skillful editorial assistance. Financial support for editorial services was provided by Bayer Healthcare, Italy.
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- Heit JA. The epidemiology of venous thromboembolism in the community. Arterioscler Thromb Vasc Biol. 2008;28:370–2.View ArticlePubMedPubMed CentralGoogle Scholar
- Cohen AT, Agnelli G, Anderson FA, Arcelus JI, Bergqvist D, Brecht JG, et al. Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost. 2007;98:756–64.PubMedGoogle Scholar
- Stein PD, Henry JW. Prevalence of acute pulmonary embolism among patients in a general hospital and at autopsy. Chest. 1995;108:978–81.View ArticlePubMedGoogle Scholar
- Heit III JA, Silverstein MD, Mohr DN, Petterson TM, O’Fallon WM, Melton III LJ. Risk factors for deep vein thrombosis and pulmonary embolism: a population based case–control study. Arch Intern Med. 2000;160:809–15.View ArticlePubMedGoogle Scholar
- Büller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366:1287–97.View ArticlePubMedGoogle Scholar
- The Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). 2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2014;35:3145–6.View ArticleGoogle Scholar
- Aujesky D, Obrosky DS, Stone RA, Auble TE, Perrier A, Cornuz J, et al. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med. 2005;172:1041–6.View ArticlePubMedPubMed CentralGoogle Scholar
- Jiménez D, Aujesky D, Díaz G, Monreal M, Otero R, Martí D, et al. Prognostic significance of deep vein thrombosis in patients presenting with acute symptomatic pulmonary embolism. Am J Respir Crit Care Med. 2010;181:983–91.View ArticlePubMedGoogle Scholar
- Fraga M, Taffé P, Méan M, Hugli O, Witzig S, Waeber G, et al. The inter-rater reliability of the Pulmonary Embolism Severity Index. Thromb Haemost. 2010;104:1258–62.View ArticlePubMedGoogle Scholar
- Goldhaber SZ, Bounameaux H. Pulmonary embolism and deep vein thrombosis. Lancet. 2012;379:1835–46.View ArticlePubMedGoogle Scholar
- Kubitza D, Becka M, Roth A, Mueck W. Dose-escalation study of the pharmacokinetics and pharmacodynamics of rivaroxaban in healthy elderly subjects. Curr Med Res Opin. 2008;24:2757–65.View ArticlePubMedGoogle Scholar
- Kubitza D, Becka M, Voith B, Zuehlsdorf M, Wensing G. Safety, pharmacodynamics, and pharmacokinetics of single doses of BAY 59–7939, an oral, direct factor Xa inhibitor. Clin Pharmacol Ther. 2005;78:412–21.View ArticlePubMedGoogle Scholar