Shock Syndromes II
| (c) | A 2012 analysis of a National Inpatient Sample containing over 70,000 patients with an |
|---|
unstable PE (defined as the presence of shock or a requirement for mechanical ventilation)
suggested reduced mortality attributable to PE with the use of systemic thrombolytics
(8.4% vs. 42%; p<0.0001).
| (d) | Systemic thrombolytics for a massive PE are likely underused because about 70% of |
|---|
patients in this database were not treated.
vii.
Use of thrombolytics in submassive PE is controversial and should be based on the risk-benefit
profile:
| (a) | In a study of patients with a submassive PE, adding alteplase 100 mg infused over 2 hours |
|---|
to heparin compared with heparin plus placebo (heparin alone) was associated with a
lower rate of death or clinical deterioration requiring an escalation in treatment (11.0%
vs. 24.6%, p=0.006). This result was driven by more patients in the heparin-alone arm
who received secondary thrombolytics (23.2% vs. 7.6%, p=0.001), which may have been
influenced by the investigators’ ability to break the blinding of treatment allocation in the
study. Bleeding did not differ between study arms.
| (b) | The PEITHO study evaluated patients with a submassive PE (fulfilling both RV dysfunction |
|---|
and myocardial necrosis criteria) randomized to weight-based tenecteplase plus heparin
or placebo plus heparin (heparin alone).
| (1) | Between randomization and day 7, patients allocated to tenecteplase less commonly |
|---|
died or had hemodynamic decompensation (2.6% vs. 5.6%, p=0.02; number needed to
treat 33 patients [95% CI, 18–162 patients]) but more commonly had major extracranial
bleeding (6.3% vs. 1.2%, p<0.001; number needed to harm 20 patients [95% CI, 13–35
patients]) and stroke (2.4% vs. 0.2%, p=0.003; number needed to harm 47 patients
[95% CI, 26–107 patients]).
| (2) | The difference in stroke incidence was driven by a higher incidence of hemorrhagic |
|---|
stroke in the tenecteplase arm (2.0% vs. 0.2%, p=0.01; number needed to harm 57
patients [95% CI, 30–164 patients]).
| (3) | The overlapping 95% CIs for number needed to treat and number needed to harm for |
|---|
clinically important outcomes call into question the risk-benefit profile of tenecteplase
for a submassive PE.
| (c) | Around 70% of patients from the PEITHO trial had a long-term follow-up for at least 24 |
|---|
months (average 37.8 months).
| (1) | Overall and cause-specific mortality at 30 days or long term did not differ in those |
|---|
who received tenecteplase compared with placebo.
| (2) | Of the 290 patients who had echocardiograms with long-term follow-up, CTEPH was |
|---|
confirmed in 2.1% of those who received tenecteplase compared with 3.2% who did
not (p=0.79).
| (3) | In addition, functional status, symptoms, RV dysfunction, and survival by day 30 did |
|---|
not differ between tenecteplase and placebo.
| (d) | As a result of this trial, the 2021 CHEST guidelines and the 2019 ESC/ERS guidelines |
|---|
recommend against routine use of systemic thrombolytics in intermediate- or low-risk
PE. However, in select patients with signs or risk of deterioration and a low bleeding risk,
systemic thrombolytics may be considered.
viii.
The risk-benefit of thrombolytics is best determined on a case-by-case basis by the bedside
clinician (Table 10).
| (a) | In the PEITHO trial, a subgroup analysis showed that age older than 75 may be associated |
|---|
with a risk of major extracranial bleed (OR 20.38; 95% CI, 2.69–154.53; p=0.09).