A prospective, case-control study was conducted over a period of 2 years at this center. The ethical clearance for the study design was sought and granted by the institutional ethical committee (IEC). Patients were enrolled in this study from June 2017 to May 2019. Patients presenting to this center with submassive pulmonary embolism were enrolled in this study.
The inclusion criteria include an age of 18 years or older, objectively confirmed acute submassive pulmonary embolism (as defined subsequently) with an onset of symptoms 15 days or less before seeking medical consultation, right ventricular dysfunction confirmed by echocardiography or spiral computed tomography (CT) of the chest, and myocardial injury confirmed by a positive test for troponin I or troponin T.
Patients denying consent, having contraindication to thrombolysis, or having previous history of allergy to contrast dye were excluded from the study.
Massive pulmonary embolism is defined as a conglomerate of pulselessness, persistent bradycardia with rate < 40 bpm, and signs of shock or sustained hypotension. Sustained hypotension includes systolic blood pressure (SBP) of < 90 mmHg for > 15 min, an SBP of < 100 mmHg in a patient with a history of hypertension, or a > 40% reduction in baseline SBP in the absence of dysrhythmia, hypovolemia, sepsis, or left ventricular (LV) dysfunction.
Submassive embolism is the one with normal or near-normal SBP (≥ 90 mmHg) with evidence of cardiopulmonary stress, including RV dysfunction or myocardial necrosis. RV dysfunction is defined by RV dilation on echo (RV diameter/LV diameter > 0.9), RV systolic dysfunction on echo, brain natriuretic peptide (BNP) elevation (> 90 pg/mL), N-terminal pro-BNP (> 500 pg/mL), or electrocardiographic (ECG) changes (new RBBB, anteroseptal ST ↑/↓, or anteroseptal T-wave ↓). Myocardial necrosis is defined as an elevation in troponin I or T over laboratory normal value or above patient baseline.
Non-massive PE is defined as no signs of clinical instability, hemodynamic compromise, and no RV strain on echocardiographic or elevation in biomarker.
The patient population was divided into two groups, the thrombolysis group and control group depending on whether the patient received thrombolysis plus anticoagulants or anticoagulants only by simple randomization method. The randomization was completed within 2 h of hospital admission. All the patients included in the study were concomitantly evaluated for the presence of underlying risk factors for PE development like COPD, congestive cardiac failure, previous PTE, active cancer, recent surgery or major trauma, pregnancy, immobilization, estrogen use, and DVT. Patients were also evaluated for the presence of inherited thrombogenic risk factors like factor V Leiden, prothrombin gene mutation, anti-thrombin III deficiency, protein C deficiency, protein S deficiency, ANA/APLA, JAK2, and homocysteinemia.
The patients in the thrombolysis arm received a single bolus dose of 100 mg of alteplase followed by a maintenance dose of unfractionated heparin to maintain APTT between 2 and 2.5 times the upper limit of the normal range.
The patients in the control arm received an initial bolus dose of unfractionated heparin and subsequent maintenance dose. The heparin infusion rate was adjusted to achieve and maintain an APTT that was 2 to 2.5 times the upper limit of the normal range.
All the patients were followed for 30 days and were evaluated for death, hemodynamic decompensation (or collapse), bleeding, stroke, recurrent pulmonary embolism, and serious adverse events. The primary outcome was the clinical composite of death from any cause, hemodynamic decompensation (or collapse), and need for mechanical ventilation within 7 days of hospitalization. The secondary outcomes included death within 7 days after hospitalization, hemodynamic decompensation within 7 days, confirmed symptomatic recurrence of pulmonary embolism within 7 days, death within 30 days, and major adverse events in 30 days. Safety outcomes were defined as ischemic or hemorrhagic stroke (including hemorrhagic conversion of ischemic stroke) within 7 days after hospitalization, extracranial major (moderate or severe) bleeding within 7 days, and serious adverse events within 30 days.
The analysis included profiling of patients on different demographic, clinical, and radiological findings. Quantitative data were presented in terms of means and standard deviation. Qualitative/categorical data were presented as absolute numbers and proportions. Student’s t test was used for the comparison of quantitative outcome parameters for normally distributed data, and Wilcoxon’s test was used for non-normally distributed data. For paired comparison, Student’s t test and sign rank test were used for normally and non-normally distributed data, respectively. p value <0.05 is considered statistically significant. SPSS software version 20.0 was used for statistical analysis.