Introduction

  • Percutaneous coronary intervention (PCI) is the preferred reperfusion strategy during a cardiac arrest; thrombolytic therapy is an option without PCI capability, followed by transfer to a PCI-capable center.
  • Thrombolytic therapy is most effective when administered within 30 minutes of first medical contact, however, may be considered within 12–24 hours of symptom onset and ongoing ischemia or extensive ST elevation.
  • During ACS-induced cardiac arrest, the goal for fibrinolysis is 30 minutes and reperfusion with PCI is preferred; however, if PCI is delayed, fibrinolytic therapy could be considered.
  • Current guidance continues to favor primary PCI as first-line reperfusion when it can be delivered within the guideline-recommended window (first-medical-contact-to-device ≤ 120 minutes); fibrinolysis followed by transfer for angiography (a “pharmaco-invasive” strategy) is the recommended alternative when that timeframe cannot be met (2021 ACC/AHA/SCAI coronary revascularization guideline). Note that the STREAM trials described below enrolled patients specifically unable to undergo primary PCI within 1 hour of first medical contact.

Clinical Detail

Pharmacology

AlteplaseTenecteplase
MOAInitiates fibrinolysis by binding to fibrin in a thrombus and converts entrapped plasminogen to plasminPromotes initiation of fibrinolysis by binding to fibrin and converting plasminogen to plasmin; similar to alteplase but more fibrin-specific
Dose (STEMI, accelerated infusion)>67 kg: 15 mg IV bolus, then 50 mg over the first 30 min, then 35 mg over the next 60 min (max total 100 mg)
≤67 kg: 15 mg IV bolus, then 0.75 mg/kg over the first 30 min (max 50 mg), then 0.5 mg/kg over the next 60 min (max 35 mg)		<60 kg: 30 mg
≥60 to <70 kg: 35 mg
≥70 to <80 kg: 40 mg
≥80 to <90 kg: 45 mg
≥90 kg: 50 mg
AdministrationIV bolus over 1–2 minutes, followed by the weight-based infusion aboveSingle IV bolus over 5 seconds
PK/PDDuration: ∼1 hour after infusion terminated
Distribution: approximates plasma volume
Half-life: ∼5 minutes (initial)
Excretion: hepatic and plasma clearance		Distribution: weight-related
Metabolism: hepatic
Half-life: biphasic; initial 20–24 min, terminal 90–130 min
Excretion: plasma clearance
Adverse EffectsIntracranial hemorrhage, ecchymosis, GI/GU hemorrhage, sepsis, cerebrovascular accidentHemorrhage and hematoma, cerebrovascular accident
Drug Interactions and WarningsAvoid combination with tranexamic acid; risk of internal bleeding, thromboembolic events, cholesterol embolizationAvoid combination with tranexamic acid; risk of internal bleeding, thromboembolic events, arrhythmias
ContraindicationsActive internal bleeding; ischemic stroke within 3 months (except when within 4.5 hours); severe uncontrolled hypertensionActive internal bleeding; severe uncontrolled hypertension; recent intracranial/intraspinal surgery; ischemic stroke within 3 months
CompatibilityMay be further diluted immediately before administration in an equal volume of 0.9% sodium chloride or 5% dextrose (D5W)Incompatible with dextrose-containing IV lines — precipitation can occur; flush dextrose lines with a saline solution before and after the bolus

Doses, administration, and compatibility cross-checked against the current Activase (alteplase) and TNKase (tenecteplase) FDA prescribing information (DailyMed), July 2026.

Evidence

Author, yearDesign / sample sizeIntervention & comparisonOutcome
Guillermin et al., 2016Systematic review & meta-analysis of 3 RCTs
N = 17,325		Tenecteplase (30–50 mg) vs. weight-based accelerated alteplaseTenecteplase reduced major bleeding vs. alteplase (RR 0.79; 95% CI 0.69–0.90; P=0.0002). No difference in intracranial hemorrhage (RR 0.96; P=0.82) or 30-day mortality (RR 1.02). Tenecteplase carries a lower major-bleeding risk than alteplase with equivalent efficacy.
Llevadot et al., 2001Narrative review (38 of 138 identified articles analyzed)Reteplase, lanoteplase, and tenecteplase vs. accelerated alteplaseTenecteplase and reteplase were comparable to accelerated alteplase in efficacy/safety, with more convenient bolus administration. Lanoteplase plus heparin was as effective as alteplase for mortality but had significantly higher intracranial hemorrhage. Bolus fibrinolytics simplify administration; lanoteplase's higher ICH signal halted its further development.
Boersma et al., 1996Pooled analysis of 22 randomized trials
N = 50,246		Fibrinolytic therapy vs. placebo/control, by treatment delayProportional mortality reduction was significantly greater when treated within 2 hours of symptom onset vs. later (44% vs. 20%; P=0.001). Earlier fibrinolysis substantially increases the mortality benefit — the “golden hour” effect.
GUSTO Investigators, 1993Randomized controlled trial
N = 41,021		Streptokinase+SQ heparin vs. streptokinase+IV heparin vs. accelerated alteplase+IV heparin vs. streptokinase+alteplase+IV heparin30-day mortality: 7.2%, 7.4%, 6.3%, and 7.0% respectively — a 14% relative mortality reduction with accelerated alteplase vs. the streptokinase-only arms (P=0.001). Hemorrhagic stroke was more frequent with accelerated alteplase (0.72% vs. 0.49–0.54%; P=0.03). Accelerated alteplase with IV heparin improves survival over streptokinase but at the cost of more hemorrhagic stroke.
Armstrong et al. (STREAM), 2013Randomized controlled trial
N = 1,892		Prehospital fibrinolysis (bolus tenecteplase + clopidogrel + enoxaparin, then transfer for PCI) vs. primary PCI, in STEMI patients unable to undergo PCI within 1 hourComposite of death/shock/CHF/reinfarction at 30 days: 12.4% (fibrinolysis) vs. 14.3% (PCI); not statistically significant (P=0.21). Intracranial hemorrhage was higher with fibrinolysis before a protocol amendment halved the tenecteplase dose in patients ≥75 years (1.0% vs. 0.2%, P=0.04); after the amendment the difference was no longer significant (0.5% vs. 0.3%, P=0.45). A pharmaco-invasive strategy achieves reperfusion comparable to primary PCI when PCI access is delayed, provided the tenecteplase dose is halved in patients ≥75 years.
Cardiac Arrest Data
Böttiger et al., 2001Prospective cohort
N = 90 (40 treated, 50 control)		Alteplase 50 mg bolus (repeat 50 mg at 30 min if no ROSC) + heparin vs. conventional CPR alone, after CPR unsuccessful at 15 minROSC 68% vs. 44% (P=0.026); admission to cardiac ICU 58% vs. 30% (P=0.009); alive at 24h 35% vs. 22% (P=0.171, not significant); discharged from hospital 15% vs. 8%. No bleeding complications related to CPR. Rescue thrombolysis after failed CPR improved ROSC and ICU admission; longer-term survival differences were not statistically significant in this small cohort.
Schreiber et al., 2002Retrospective cohort
N = 157 (42 received thrombolysis, 27%)		Thrombolytic therapy (accelerated alteplase regimen) vs. none, after witnessed VF cardiac arrest due to AMIGood neurological recovery (CPC 1–2) at 6 months: 69% vs. 50% (P=0.03). After adjustment for age, epinephrine dose, and CPR duration, the trend toward better neurological recovery no longer reached significance (OR 1.9; 95% CI 0.8–4.6). Thrombolytic therapy was associated with better unadjusted neurologic outcome, but the adjusted association did not reach significance.
Lederer et al., 2004Long-term follow-up of 27 survivors from a 108-patient rt-PA-during-CPR cohort (Lederer 2001)Recombinant tPA given during CPR for out-of-hospital cardiac arrest22 of 27 survivors (81%) were discharged without neurological deficit (CPC 1); 18 of 27 (67%) were still alive at follow-up. Among survivors of rt-PA-assisted CPR, most retained good neurological function long-term.
Li et al., 2006Meta-analysis of 8 studies (MEDLINE 1966–2004)CPR with vs. without thrombolytic agentsThrombolytic agents significantly improved ROSC, 24-hour survival, survival to discharge, and long-term neurological function (all P<0.01) — but were also associated with a significantly increased risk of severe bleeding (P<0.01). Thrombolysis during CPR may improve survival and neurologic outcome, but this benefit comes with a real, statistically significant increase in severe bleeding risk.
Böttiger et al. (TROICA), 2008Double-blind, multicenter RCT, terminated early for futility
N = 1,050		Weight-based tenecteplase vs. placebo during CPR for out-of-hospital cardiac arrest, no adjunctive heparin/aspirinNo significant difference in 30-day survival (14.7% vs. 17.0%; P=0.36), ROSC (55.0% vs. 54.6%; P=0.96), or neurologic outcome (P=0.69). More intracranial hemorrhages occurred with tenecteplase. The largest RCT of thrombolysis during CPR found no survival benefit and more bleeding — this directly tempers the benefit signal seen in the smaller cohort studies above.
Ruiz-Bailén et al., 2001Retrospective cohort (Spanish ARIAM registry)
N = 303 (67 thrombolysis, 236 no treatment)		Systemic thrombolysis (streptokinase, accelerated alteplase, or double-bolus alteplase) vs. none, after resuscitation from AMI-related cardiac arrestICU/CCU mortality 17.9% vs. 46.2% (P<0.00001); mechanical ventilation 42.9% vs. 80.8% (P<0.00001); repeat CPR attempts 33.3% vs. 61.0% (P<0.0001); no fatal hemorrhagic complications in either group. In this registry cohort, thrombolysis was associated with markedly lower mortality and no increase in fatal bleeding — contrasting with TROICA's null RCT result above.
Recent Evidence (2023–2026)
Van de Werf et al. (STREAM-2), 2023Open-label RCT
N = 604 (401 pharmaco-invasive, 203 primary PCI), age ≥60y		Half-dose tenecteplase pharmaco-invasive strategy vs. primary PCI, STEMI patients unable to undergo PCI within 1 hour≥50% ST resolution: 85.2% (pharmaco-invasive) vs. 78.4% (PCI). 30-day composite (death/shock/HF/reinfarction): 12.8% vs. 13.3% (RR 0.96; 95% CI 0.62–1.48). 6 intracranial hemorrhages occurred in the pharmaco-invasive arm (1.5%, half were protocol violations) vs. 0 with PCI (3 of the 6 were protocol violations: excess anticoagulation or uncontrolled hypertension). Halving the tenecteplase dose in patients ≥60 years achieves comparable efficacy to primary PCI, with a modest increase in ICH risk that was partly protocol-deviation-driven.
Bainey et al., 2025Inter-trial comparison of STREAM-1 (full-dose) and STREAM-2 (half-dose)
N = 1,103, age 60–<75y		Full-dose vs. half-dose tenecteplase pharmaco-invasive strategy vs. primary PCI≥50% ST resolution similar between full- and half-dose tenecteplase (68.7% vs. 71.2%; P=0.519); ICH 1.5% vs. 2.1% (P=0.605, not significant). Major non-ICH bleeding was markedly lower with half-dose (STREAM-2: 0.3–0.7%) than full-dose (STREAM-1: 6.0–7.1%). In patients 60–74 years, half-dose tenecteplase appears as effective as full-dose with substantially less major non-ICH bleeding (ICH rates were similar, numerically slightly higher with half-dose but not significant).
Bainey et al., 2026Pre-specified analysis of STREAM-2
N = 583 (386 pharmaco-invasive, 197 primary PCI)		Rescue PCI (after failed fibrinolysis) vs. scheduled angiography (after successful fibrinolysis)Rescue PCI was required in 43.5% of pharmaco-invasive patients (168 of 386) and was associated with less ST resolution (76.3% vs. 92.5%; P<0.001), worse 30-day composite outcomes (16.7% vs. 6.0%; P<0.001), and higher intracranial hemorrhage (2.4% vs. 0.5%) than patients with successful fibrinolysis. Failed fibrinolysis requiring rescue PCI is a higher-risk subgroup — rapid transfer to a PCI-capable center remains essential even after fibrinolytic therapy is given.

Conclusions

  • Primary PCI remains the preferred reperfusion strategy for STEMI, including when cardiac arrest is present; fibrinolytic therapy is the recommended alternative when timely primary PCI (first-medical-contact-to-device within ∼120 minutes) cannot be achieved, followed by transfer to a PCI-capable center.
  • Both alteplase and tenecteplase are appropriate fibrinolytic agents for STEMI. Tenecteplase's single weight-based bolus (30–50 mg) is simpler to administer than alteplase's bolus-plus-infusion regimen, and a meta-analysis of 3 RCTs (n=17,325) found tenecteplase carries a lower major-bleeding risk with equivalent 30-day mortality and no difference in intracranial hemorrhage.
  • The 2013 STREAM trial and the 2023–2026 STREAM-2 analyses establish a pharmaco-invasive strategy — prehospital fibrinolysis with tenecteplase followed by transfer for angiography — as comparable in efficacy to primary PCI when timely PCI is unavailable. Age-adjusted dosing matters: in STREAM (2013), full-dose tenecteplase caused excess intracranial hemorrhage in patients ≥75 years, prompting a mid-trial amendment to half-dose for that age group. STREAM-2 (2023) then tested half-dose tenecteplase in all patients ≥60 years and found efficacy comparable to primary PCI with an ICH rate of 1.5% (vs. 0% with PCI; 3 of the 6 ICH events were protocol violations) — supporting reduced dosing whenever a pharmaco-invasive strategy is used in older patients.
  • Evidence on thrombolysis specifically during ongoing CPR for cardiac arrest is mixed and should be weighed by study quality: several smaller cohort studies (Böttiger 2001, Schreiber 2002, Ruiz-Bailén 2001, and the Li 2006 meta-analysis) suggest improved ROSC, survival, or neurological outcome with thrombolysis, but the largest and only large double-blind RCT (TROICA, Böttiger 2008, n=1,050) found no benefit in 30-day survival, ROSC, or neurologic outcome, and more intracranial hemorrhage with tenecteplase. Thrombolysis during CPR is not routinely recommended based on this RCT-level evidence, though it may be considered when pulmonary embolism or STEMI is strongly suspected as the cause of arrest and conventional CPR has failed.
  • When fibrinolysis is used for STEMI and fails (inadequate ST resolution), rescue PCI is required in a substantial proportion of patients (43.5% in STREAM-2) and this subgroup has worse outcomes than those with successful fibrinolysis — reinforcing that rapid transfer to a PCI-capable center is essential regardless of the reperfusion strategy chosen.

References

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Tags:STEMI fibrinolytics alteplase tenecteplase cardiac arrest