International Journal of Cardiology 176 (2014) 1290–1291
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Fibrinolysis in intermediate risk pulmonary embolism: Too much risk for too little reward? Paras Karmacharya, Ranjan Pathak ⁎, Madan Raj Aryal, Anthony A. Donato Reading Health System, West Reading, PA 19611, United States
a r t i c l e
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Article history: Received 19 June 2014 Accepted 27 July 2014 Available online 5 August 2014 Keywords: Fibrinolysis Intermediate risk Pulmonary embolism National Inpatient Sample HCUP
In patients with acute pulmonary embolism (PE), the debate regarding the role of thrombolysis revolves around balancing the risks of major bleeding with the benefits of prevention of further (possibly life-threatening) embolic events. In the highest risk patients who are hemodynamically unstable, major societies agree that thrombolysis is the best course of action [1]. However, for the subset of intermediate risk patients who demonstrate radiographic or biochemical markers of right ventricular strain, the role of thrombolysis has been hotly debated. Meta-analysis of smaller studies, including a total of 464 patients, showed no clear mortality benefit but no increase in major bleeding with fibrinolysis in this group [2]. A recent randomized, controlled trial by Meyer et al. [3] including 1005 patients suggested that early thrombolytic therapy prevented hemodynamic instability but increased risk of hemorrhage and stroke. However, this study was not powered to detect a mortality benefit between groups. To confirm these findings in a larger non-randomized sample, we used the Nationwide Inpatient Sample (NIS), Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality [4]. NIS is the largest all-payer inpatient care database, publicly available in the United States and contains data from 5 to 8 million hospital stays from nearly 1000 hospitals. Using the 2006–2011 NIS data, we identified patients with PE and evidence of elevated cardiac enzymes, eliminating those with shock and DVT (to remove those receiving catheter-directed vein therapies) and compared
⁎ Corresponding author at: Reading Health System, 6th Avenue and Spruce Street, West Reading, PA 19611, United States. Tel.: +1 484 628 8255; fax: +1 484 628 9003. E-mail address: [email protected] (R. Pathak).
http://dx.doi.org/10.1016/j.ijcard.2014.07.178 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
cohorts with and without charges for thrombolytic therapy using Chisquare and Z-tests (Fig. 1). In the 26,820 patients identified, we found that in-hospital mortality in the thrombolysis group was significantly higher (26.73% vs. 19.93%, OR 1.47, 95% CI 1.20–1.79, p b 0.001). Thrombolysis did not reduce the mean total length of stay (11.06 vs. 10.99 days, p = ns), while incurring greater mean hospital charges ($121,785 vs. $89,593, p b 0.05). We therefore echo the calls by Elliot [5] to use thrombolysis as a rescue therapy until either lower doses are found to improve the risk/ benefit ratio or longer-term benefits (i.e. prevention of chronic thromboembolic pulmonary hypertension) are realized in randomized trials. Studies comparing the standard dose of thrombolytic therapy with lower doses and longer follow-up periods may help answer these important questions. Funding None. Contribution PK, RP, MRA and AAD participated in concept, design, analyses, drafting and final edits of draft. Conflict of interest None. References [1] Jaff MR, McMurtry MS, Archer SL, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation 2011;123(16):1788–830. [2] Tardy B, Venet C, Zeni F, Coudrot M, Guyomarc'h S, Mismetti P. Short term effect of recombinant tissue plasminogen activator in patients with hemodynamically stable acute pulmonary embolism: results of a meta-analysis involving 464 patients. Thromb Res 2009;124(6):672–7. [3] Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med 2014;370(15):1402–11. [4] Healthcare Cost and Utilization Project (HCUP). HCUP Nationwide Inpatient Sample (NIS). Rockville, MD: Agency for Healthcare Research and Quality; 2006–2011 [www.hcup-us.ahrq.gov/nisoverview.jsp. Accessed April 20, 2014]. [5] Elliott CG. Fibrinolysis of pulmonary emboli—steer closer to Scylla. N Engl J Med 2014; 370(15):1457–8.
P. Karmacharya et al. / International Journal of Cardiology 176 (2014) 1290–1291
Fig. 1. Selection of cases.
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Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Fibrinolysis in intermediate risk pulmonary embolism: Too much risk for too little reward? Paras Karmacharya, Ranjan Pathak ⁎, Madan Raj Aryal, Anthony A. Donato Reading Health System, West Reading, PA 19611, United States
a r t i c l e
i n f o
Article history: Received 19 June 2014 Accepted 27 July 2014 Available online 5 August 2014 Keywords: Fibrinolysis Intermediate risk Pulmonary embolism National Inpatient Sample HCUP
In patients with acute pulmonary embolism (PE), the debate regarding the role of thrombolysis revolves around balancing the risks of major bleeding with the benefits of prevention of further (possibly life-threatening) embolic events. In the highest risk patients who are hemodynamically unstable, major societies agree that thrombolysis is the best course of action [1]. However, for the subset of intermediate risk patients who demonstrate radiographic or biochemical markers of right ventricular strain, the role of thrombolysis has been hotly debated. Meta-analysis of smaller studies, including a total of 464 patients, showed no clear mortality benefit but no increase in major bleeding with fibrinolysis in this group [2]. A recent randomized, controlled trial by Meyer et al. [3] including 1005 patients suggested that early thrombolytic therapy prevented hemodynamic instability but increased risk of hemorrhage and stroke. However, this study was not powered to detect a mortality benefit between groups. To confirm these findings in a larger non-randomized sample, we used the Nationwide Inpatient Sample (NIS), Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality [4]. NIS is the largest all-payer inpatient care database, publicly available in the United States and contains data from 5 to 8 million hospital stays from nearly 1000 hospitals. Using the 2006–2011 NIS data, we identified patients with PE and evidence of elevated cardiac enzymes, eliminating those with shock and DVT (to remove those receiving catheter-directed vein therapies) and compared
⁎ Corresponding author at: Reading Health System, 6th Avenue and Spruce Street, West Reading, PA 19611, United States. Tel.: +1 484 628 8255; fax: +1 484 628 9003. E-mail address: [email protected] (R. Pathak).
http://dx.doi.org/10.1016/j.ijcard.2014.07.178 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
cohorts with and without charges for thrombolytic therapy using Chisquare and Z-tests (Fig. 1). In the 26,820 patients identified, we found that in-hospital mortality in the thrombolysis group was significantly higher (26.73% vs. 19.93%, OR 1.47, 95% CI 1.20–1.79, p b 0.001). Thrombolysis did not reduce the mean total length of stay (11.06 vs. 10.99 days, p = ns), while incurring greater mean hospital charges ($121,785 vs. $89,593, p b 0.05). We therefore echo the calls by Elliot [5] to use thrombolysis as a rescue therapy until either lower doses are found to improve the risk/ benefit ratio or longer-term benefits (i.e. prevention of chronic thromboembolic pulmonary hypertension) are realized in randomized trials. Studies comparing the standard dose of thrombolytic therapy with lower doses and longer follow-up periods may help answer these important questions. Funding None. Contribution PK, RP, MRA and AAD participated in concept, design, analyses, drafting and final edits of draft. Conflict of interest None. References [1] Jaff MR, McMurtry MS, Archer SL, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation 2011;123(16):1788–830. [2] Tardy B, Venet C, Zeni F, Coudrot M, Guyomarc'h S, Mismetti P. Short term effect of recombinant tissue plasminogen activator in patients with hemodynamically stable acute pulmonary embolism: results of a meta-analysis involving 464 patients. Thromb Res 2009;124(6):672–7. [3] Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med 2014;370(15):1402–11. [4] Healthcare Cost and Utilization Project (HCUP). HCUP Nationwide Inpatient Sample (NIS). Rockville, MD: Agency for Healthcare Research and Quality; 2006–2011 [www.hcup-us.ahrq.gov/nisoverview.jsp. Accessed April 20, 2014]. [5] Elliott CG. Fibrinolysis of pulmonary emboli—steer closer to Scylla. N Engl J Med 2014; 370(15):1457–8.
P. Karmacharya et al. / International Journal of Cardiology 176 (2014) 1290–1291
Fig. 1. Selection of cases.
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