According to 2013 American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) guidelines on the management of ST-elevation myocardial infarction (STEMI), in the absence of contraindications, fibrinolytic therapy should be given to patients with STEMI and onset of ischemic symptoms within the previous 12 hours when it is anticipated that primary percutaneous coronary intervention (PCI) cannot be performed within 120 minutes of first medical contact. In the absence of contraindications and when PCI is not available, fibrinolytic therapy is reasonable for patients with STEMI if there is clinical and/or electrocardiogram evidence of ongoing ischemia within 12 to 24 hours of symptom onset and a large area of myocardium at risk or hemodynamic instability. Fibrin-specific agents are preferred when available (i.e., tenecteplase, reteplase, or alteplase), but preference for one specific agent over another is not addressed. Of note, tenecteplase is given as a single intravenous weight-based bolus and is identified to have increased fibrin specificity compared to reteplase and alteplase. Additionally, available data have found the patency rate (90-minute thrombolysis in myocardial infarction [TIMI] 2 or 3 flow) to be 85% with tenecteplase compared to 73% to 84% with alteplase. [1]
According to 2008 American College of Chest Physicians (ACCP) guidelines on acute STEMI, for patients with ischemic symptoms characteristic of acute MI of ≤ 12-hour duration and persistent STE, it is recommended to administer streptokinase, anistreplase, alteplase, reteplase, or tenecteplase over no fibrinolytic therapy (all Grade 1A). For patients with symptom duration ≤ 6 hours, it is recommended to administer alteplase (Grade 1A) or tenecteplase (Grade 1 A). Of note, for patients receiving fibrinolytic therapy, it is suggested to use a bolus agent (e.g., tenecteplase) to facilitate the ease of administration and potentially reduce the risk of intracranial hemorrhage (ICH)-related bleeding (tenecteplase). This recommendation is based on results observed in the ASSENT-2 trial (see Table 5). [2]
According to 2016 CHEST guidelines, a systemically administered thrombolytic regimen is recommended in patients with acute pulmonary embolism (PE) associated with hypotension (e.g., systolic blood pressure <90 mm Hg) who do not have a high bleeding risk. On the other hand, the guideline does not recommend thrombolytic therapy in patients with acute PE without hypotension. In selected patients with acute PE who continue to deteriorate regardless of the underlying anticoagulant therapy but have yet to develop hypotension and have a low bleeding risk, the panel suggests systemically administered thrombolytic therapy over no such therapy. Preference for a specific agent is not addressed. [3]
According to 2020 American Society of Hematology (ASH) guidelines, thrombolysis therapy, in addition to anticoagulation, is a reasonable consideration in submassive PE, defined as right ventricular dysfunction without hemodynamic instability. Patients with low bleeding risk, such as those with younger age, or high decompensation risk due to concurrent cardiopulmonary disease are potential candidates. The guideline does not provide further data or a preference for one thrombolytic over another. In general, systemic thrombolysis is preferred over catheter-directed therapy unless in patients with a high risk of bleeding, contraindications to systemic thrombolytic therapy, and/or persistent hemodynamic instability despite systemic thrombolysis. [4]
The 2019 European Society of Cardiology guidelines for management of acute PE recommend rescue thrombolytic therapy for patients who deteriorate hemodynamically (Class I). The guideline states that thrombolytic agents are associated with a significant reduction in mortality and recurrent PE combined in patients with high-risk PE, mostly in cardiogenic shock. Intravenous administration of recombinant tissue-type plasminogen activator (rtPA; 100 mg infused over 2 hours) remains the preferable agent and strategy. On the other hand, even investigated in clinical trials, tenecteplase has not yet been approved for this indication. The authors state the impact of early thrombolysis for (intermediate or high-risk) acute PE on long-term benefits on clinical symptoms, functional limitation, or chronic thromboembolic pulmonary hypertension is still unclear. [5]
A 2020 review examining the use of systemic thrombolytic therapy for massive and submassive PE included 67 articles, of which 24 clinical trials related explicitly to either intravenous (IV) tenecteplase or alteplase. The authors noted the absence of direct comparative data between the two agents yet suggest potential benefits of fibrin-specific, second- (alteplase) and third- (tenecteplase) generation given as 2-hour IV infusion and IV push, respectively, over first-generation, non-fibrin-specific thrombolytic (e.g., urokinase, streptokinase) which typically requires prolonged IV infusions (12- to 24-hour) and may delay clot lysis while increasing the risk of bleeding. The authors concluded a lack of clinical data to draw preference over another between fibrin-specific thrombolytics for either massive or submissive PE. [6]
According to a systematic review in 2016, IV thrombolysis or mechanical thrombectomy can be used to treat hemodynamically unstable PE patients. As a third-generation thrombolytic, tenecteplase is approved for the treatment of acute coronary syndromes. It has also been evaluated in patients with acute PE. While there were no head-to-head comparison trials between thrombolytic agents, eight clinical trials assessed the effectiveness of thrombolytic agents, including tenecteplase, in patients with intermediate-risk PE. Overall, thrombolytic agents were found to be associated with lower all-cause mortality compared with anticoagulants (2.17% versus 3.89%, respectively), but they increased the risk of major bleeding (9.24% versus 3.42%) and intracranial hemorrhage (1.46% versus 0.19%). [7]
A 2003 review on early thrombolysis treatment suggested that there are no differences in mortality, total stroke, hemorrhagic stroke, or reinfarction between tenecteplase and alteplase, but tenecteplase may result in fewer major bleeds compared with alteplase. According to another review published in 2009, tenecteplase is easy to use in the ambulance and has a decreased risk of major non-cerebral bleeds due to its highest in-class fibrin specificity and binding. It was indicated that nitrates do not affect tenecteplase levels, whereas they do with alteplase levels. [8], [9]