Pulmonary embolism is a life-threatening condition that often requires more than anticoagulation. Invasive therapies hold promise but must be held to rigorous standards
I was very suspicious of HI-PEITHO just for the simple fact that catheter-guided thrombolysis was never tested against peripheral thrombolysis and this trial lacked that arm.
But, as we resumed, this is even worse. At best, the numerical results from the most hard outcomes - PE related deaths and cardiac arrest/CPR - worsened. If PE care changed...maybe for the worst.
In any case, why is an ultrasound-assisted catheter needed when a simple pigtail catheter can deliver direct thrombolysis? Ultrasound-assisted systems significantly increase costs. To date, there is no randomized evidence demonstrating superiority of ultrasound-assisted catheter-directed thrombolysis over standard catheter-directed thrombolysis. In this context, it would seem more logical to first evaluate the simplest and less expensive approach.
The physicians in the room cheered a “positive” result driven entirely by the softest (by a country mile) component of the composite endpoint, determined in an unblinded fashion.
This is not a good look. But sadly all too common these days.
Your careful evaluations of these many studies I think is extremely valuable in helping us all understand the "hype" and learn when we are perhaps being "hoodwinked".
This is especially important for all medical students to understand.
They should be required reading and discussing.
Thanks, Alan Magner MD (recently retired Internist)
It would be interesting to see the outcomes of the study using the PESI rather than the NEWS scoring system as it is PE specific.
Comparison of NEWS/NEWS2 vs. PESI/sPESI for Pulmonary Embolism (PE) Risk Assessment
The National Early Warning Score (NEWS/NEWS2) and Pulmonary Embolism Severity Index (PESI/sPESI) are both validated tools for assessing risk in acute PE, but they serve complementary roles. NEWS/NEWS2 is a general physiologic early-warning score used for ongoing monitoring of deterioration in any acutely ill patient. PESI (and its simplified version sPESI) is a PE-specific prognostic tool designed for initial risk stratification at diagnosis, particularly to identify low-risk patients suitable for outpatient management.
Key Differences
• Purpose: NEWS/NEWS2 detects real-time physiologic deterioration (e.g., triggers escalation like rapid response teams). In the HI-PEITHO trial (2026), a high NEWS ≥9 threshold (on two consecutive readings) was used as an objective component of the composite cardiorespiratory decompensation endpoint. PESI/sPESI predicts 30-day all-cause mortality and complicated course at presentation to guide triage (inpatient vs. outpatient, ICU consideration).
• Components: NEWS2 (7 parameters, score 0–20): Fully objective bedside vitals—respiratory rate, SpO₂ (two scales), supplemental oxygen, temperature, systolic BP, heart rate, ACVPU consciousness. Dynamic and repeatable. PESI (11 items, classes I–V) or sPESI (6 binary items, 0 vs. ≥1): Includes age, sex, cancer, chronic cardiopulmonary disease, heart rate ≥110, systolic BP <100, respiratory rate ≥30, temperature <36°C, altered mental status, and O₂ saturation <90%. Static (calculated once).
• Performance in PE (Evidence Summary): Both have moderate-to-good discrimination (AUC typically 0.6–0.85) for short-term adverse outcomes.
◦ PESI/sPESI: Extensively validated in tens of thousands of patients worldwide for 30-day mortality (low-risk groups: ~1–3% mortality). High negative predictive value for safe discharge. Superior for baseline triage and long-term prognosis. Guidelines (ESC 2019, AHA/ACC 2026) strongly endorse it.
◦ NEWS/NEWS2: Strong for dynamic monitoring and early decompensation/ICU admission in PE cohorts (sensitivity often 92–100% at low thresholds like ≥3). Comparable or slightly better than PESI for very short-term events (e.g., 7-day ICU need) in head-to-head studies, but less PE-specific. Direct comparisons (2023–2026 studies) show similar overall accuracy; PESI edges out for mortality/complications in many analyses, while NEWS excels at capturing progressive physiologic changes. Neither is perfect—both perform modestly (AUC ~0.6–0.8) for composites like decompensation.
HI-PEITHO Context The trial used NEWS for its repeatable, objective endpoint in an open-label setting. Critics noted it contributed to a “soft” primary outcome. PESI/sPESI would have been better for initial enrollment stratification but less useful for repeated post-randomization monitoring.
Practical Considerations and Conclusion Both are simple, bedside-friendly, and often automated in electronic records. NEWS is ideal for hospitalized patients needing continuous surveillance. PESI/sPESI is preferred for initial PE-specific prognosis and triage decisions. They are complementary—many clinicians use PESI at diagnosis + NEWS for ongoing monitoring.
PESI/sPESI has greater PE-specific validity and replication (decades of data, guideline integration, proven impact on outpatient care), making it the stronger standalone tool for risk stratification in most guidelines. NEWS provides excellent real-time sensitivity for deterioration but is not a replacement. In practice, combine with imaging (RV function) and biomarkers for best results. Neither supports routine advanced therapy in all intermediate-risk PE without individualized assessment.
I was very pleased to read this cogent review of this study, because even though I had put on my Mandrola hat to evaluate the study, I committed the cardinal sin of not reviewing the supplement. Thank you, John!
So why would a company invest what must have been a large amount of money in developing/acquiring this tech, and then more money and time to run a large trial to evaluate it?
Charitably (perhaps naively), I imagine they have a large amount of preclinical data to support its use in their IDE application. Thus, either their non-human data didn’t model human PEs well, or they chose bad outcomes to measure in the clinical trial.
The NEWS scale seems so misapplied that my bet would be on the latter. (In fact, its use smacks of a frantic, post-hoc search for a positive measure. Who would agree to use this in advance?)
The question would then be what blinded clinical outcomes (other than death) would physicians and patients really care about? Time to clot dissolution? Amount of residual clot after x weeks? Changes in oxygenation? Understanding what good, measurable outcomes should have been used would go a long way to helping us appreciate the overhyped nature of this study.
Thanks for sharing. In the NEWS scoring system, level of consciousness, and perhaps respiratory rate, may vary substantially from one observer to another, especially if respiratory rate is counted manually rather than recorded directly by a monitor. Otherwise, the vital signs should not be greatly affected. If measurements were truly taken 15 minutes apart and the thresholds for assigning scores of 2 or 3 were applied consistently, those components should be less susceptible to bias. Do you think some components of the NEWS scoring system are more vulnerable to this problem than others? Clearly, they do not provide that level of detail, such as whether the NEWS threshold was driven mainly by level of consciousness or by other components.
Josh Farkas has a nice take on the trial here, and cites another point:
Do we need to use an expensive vibrating catheter?
No, we don't. As mentioned above and discussed further in this blog, emerging data show that peripheral thrombolysis is equally effective as compared to catheter-directed thrombolysis.
In fact, peripheral thrombolysis has numerous advantages over catheter-directed thrombolysis:
Peripheral thrombolysis can be deployed in any hospital unit
Peripheral thrombolysis can be started immediately, without any time delay
Peripheral thrombolysis is less invasive, allowing us to avoid procedural complications.
Peripheral thrombolysis is less expensive. An ultrasonic catheter used for local thrombolytic administration costs ~$5,000. When you add procedure costs, this is an insane cost for an intervention that has never been shown to be beneficial.
Is there any way we can ask our colleagues to stop this trend of standing ovations for trials? Most of the positive trials these days are incremental (and many are worse). Sure the teams should be proud of what they are doing, and I commend them for working on the trials, but it is turning out profession into a circus/clown show. Let's get back to serious science please.
I don't think the problem are the trials concept, which are a genius and probably way of proving an intervention when well done.
The problem is both trials poorly designed and a medical community with apparently no will of aspiring to know the truth by lacking the spirit of systematically critically appraising the trials.
Medicine really needs you and your careful and honest evaluation when industry and over enthusiastic investigators are so keen to ignore the real facts and just sell a new procedure or in this case an expensive device. As with the Left atrial plugs this technique will be adopted by enthusiasts despite the lack of evidence - again the real evidence is that it probably does more harm than good. One hopes that NICE in the U.K. will evaluate with more care and avoid giving it a licence.
Hard endpoints, please!!
I was very suspicious of HI-PEITHO just for the simple fact that catheter-guided thrombolysis was never tested against peripheral thrombolysis and this trial lacked that arm.
But, as we resumed, this is even worse. At best, the numerical results from the most hard outcomes - PE related deaths and cardiac arrest/CPR - worsened. If PE care changed...maybe for the worst.
Is NEWS really so unknown? It's absolutely the norm where I am for more than a decade.
Nice critique! Composite outcomes can be sneaky!
This is an excellent evaluation by an independent reviewer of this bogus “study”/ promotional material.
It just goes to prove my long held belief that “the heart is too important an organ to be left to a cardiologist.”
In any case, why is an ultrasound-assisted catheter needed when a simple pigtail catheter can deliver direct thrombolysis? Ultrasound-assisted systems significantly increase costs. To date, there is no randomized evidence demonstrating superiority of ultrasound-assisted catheter-directed thrombolysis over standard catheter-directed thrombolysis. In this context, it would seem more logical to first evaluate the simplest and less expensive approach.
The physicians in the room cheered a “positive” result driven entirely by the softest (by a country mile) component of the composite endpoint, determined in an unblinded fashion.
This is not a good look. But sadly all too common these days.
Your careful evaluations of these many studies I think is extremely valuable in helping us all understand the "hype" and learn when we are perhaps being "hoodwinked".
This is especially important for all medical students to understand.
They should be required reading and discussing.
Thanks, Alan Magner MD (recently retired Internist)
It would be interesting to see the outcomes of the study using the PESI rather than the NEWS scoring system as it is PE specific.
Comparison of NEWS/NEWS2 vs. PESI/sPESI for Pulmonary Embolism (PE) Risk Assessment
The National Early Warning Score (NEWS/NEWS2) and Pulmonary Embolism Severity Index (PESI/sPESI) are both validated tools for assessing risk in acute PE, but they serve complementary roles. NEWS/NEWS2 is a general physiologic early-warning score used for ongoing monitoring of deterioration in any acutely ill patient. PESI (and its simplified version sPESI) is a PE-specific prognostic tool designed for initial risk stratification at diagnosis, particularly to identify low-risk patients suitable for outpatient management.
Key Differences
• Purpose: NEWS/NEWS2 detects real-time physiologic deterioration (e.g., triggers escalation like rapid response teams). In the HI-PEITHO trial (2026), a high NEWS ≥9 threshold (on two consecutive readings) was used as an objective component of the composite cardiorespiratory decompensation endpoint. PESI/sPESI predicts 30-day all-cause mortality and complicated course at presentation to guide triage (inpatient vs. outpatient, ICU consideration).
• Components: NEWS2 (7 parameters, score 0–20): Fully objective bedside vitals—respiratory rate, SpO₂ (two scales), supplemental oxygen, temperature, systolic BP, heart rate, ACVPU consciousness. Dynamic and repeatable. PESI (11 items, classes I–V) or sPESI (6 binary items, 0 vs. ≥1): Includes age, sex, cancer, chronic cardiopulmonary disease, heart rate ≥110, systolic BP <100, respiratory rate ≥30, temperature <36°C, altered mental status, and O₂ saturation <90%. Static (calculated once).
• Performance in PE (Evidence Summary): Both have moderate-to-good discrimination (AUC typically 0.6–0.85) for short-term adverse outcomes.
◦ PESI/sPESI: Extensively validated in tens of thousands of patients worldwide for 30-day mortality (low-risk groups: ~1–3% mortality). High negative predictive value for safe discharge. Superior for baseline triage and long-term prognosis. Guidelines (ESC 2019, AHA/ACC 2026) strongly endorse it.
◦ NEWS/NEWS2: Strong for dynamic monitoring and early decompensation/ICU admission in PE cohorts (sensitivity often 92–100% at low thresholds like ≥3). Comparable or slightly better than PESI for very short-term events (e.g., 7-day ICU need) in head-to-head studies, but less PE-specific. Direct comparisons (2023–2026 studies) show similar overall accuracy; PESI edges out for mortality/complications in many analyses, while NEWS excels at capturing progressive physiologic changes. Neither is perfect—both perform modestly (AUC ~0.6–0.8) for composites like decompensation.
HI-PEITHO Context The trial used NEWS for its repeatable, objective endpoint in an open-label setting. Critics noted it contributed to a “soft” primary outcome. PESI/sPESI would have been better for initial enrollment stratification but less useful for repeated post-randomization monitoring.
Practical Considerations and Conclusion Both are simple, bedside-friendly, and often automated in electronic records. NEWS is ideal for hospitalized patients needing continuous surveillance. PESI/sPESI is preferred for initial PE-specific prognosis and triage decisions. They are complementary—many clinicians use PESI at diagnosis + NEWS for ongoing monitoring.
PESI/sPESI has greater PE-specific validity and replication (decades of data, guideline integration, proven impact on outpatient care), making it the stronger standalone tool for risk stratification in most guidelines. NEWS provides excellent real-time sensitivity for deterioration but is not a replacement. In practice, combine with imaging (RV function) and biomarkers for best results. Neither supports routine advanced therapy in all intermediate-risk PE without individualized assessment.
Sources Used (Direct Links)
1 Official RCP NEWS2 Report (2017): https://www.rcp.ac.uk/media/a4ibkkbf/news2-final-report_0_0.pdf
2 HI-PEITHO Trial (NEJM 2026): https://www.nejm.org/doi/full/10.1056/NEJMoa2516567
3 Original PESI Derivation/Validation: Aujesky et al. (key reference via MDCalc summary): https://www.mdcalc.com/calc/1304/pulmonary-embolism-severity-index-pesi
4 sPESI Validation: Righini et al. (J Thromb Haemost 2011): https://www.jthjournal.org/article/S1538-7836(22)07387-1/fulltext
5 Head-to-Head Comparison Example (NEWS vs. PESI/sPESI in PE): JournalFeed 2023 summary of key study: https://journalfeed.org/article-a-day/2023/breaking-news-best-pe-scores-news-vs-pesi-vs-spesi/
6 Recent 2026 Analysis (PESI/NEWS-2 superiority in real-world PE): https://www.sciencedirect.com/science/article/abs/pii/S0167527326000951
7 AHA/ACC 2026 PE Guidelines (PESI emphasis): https://www.ahajournals.org/doi/10.1161/CIR.0000000000001415
I was very pleased to read this cogent review of this study, because even though I had put on my Mandrola hat to evaluate the study, I committed the cardinal sin of not reviewing the supplement. Thank you, John!
So why would a company invest what must have been a large amount of money in developing/acquiring this tech, and then more money and time to run a large trial to evaluate it?
Charitably (perhaps naively), I imagine they have a large amount of preclinical data to support its use in their IDE application. Thus, either their non-human data didn’t model human PEs well, or they chose bad outcomes to measure in the clinical trial.
The NEWS scale seems so misapplied that my bet would be on the latter. (In fact, its use smacks of a frantic, post-hoc search for a positive measure. Who would agree to use this in advance?)
The question would then be what blinded clinical outcomes (other than death) would physicians and patients really care about? Time to clot dissolution? Amount of residual clot after x weeks? Changes in oxygenation? Understanding what good, measurable outcomes should have been used would go a long way to helping us appreciate the overhyped nature of this study.
Thanks for sharing. In the NEWS scoring system, level of consciousness, and perhaps respiratory rate, may vary substantially from one observer to another, especially if respiratory rate is counted manually rather than recorded directly by a monitor. Otherwise, the vital signs should not be greatly affected. If measurements were truly taken 15 minutes apart and the thresholds for assigning scores of 2 or 3 were applied consistently, those components should be less susceptible to bias. Do you think some components of the NEWS scoring system are more vulnerable to this problem than others? Clearly, they do not provide that level of detail, such as whether the NEWS threshold was driven mainly by level of consciousness or by other components.
Josh Farkas has a nice take on the trial here, and cites another point:
Do we need to use an expensive vibrating catheter?
No, we don't. As mentioned above and discussed further in this blog, emerging data show that peripheral thrombolysis is equally effective as compared to catheter-directed thrombolysis.
In fact, peripheral thrombolysis has numerous advantages over catheter-directed thrombolysis:
Peripheral thrombolysis can be deployed in any hospital unit
Peripheral thrombolysis can be started immediately, without any time delay
Peripheral thrombolysis is less invasive, allowing us to avoid procedural complications.
Peripheral thrombolysis is less expensive. An ultrasonic catheter used for local thrombolytic administration costs ~$5,000. When you add procedure costs, this is an insane cost for an intervention that has never been shown to be beneficial.
https://emcrit.org/pulmcrit/hipeitho/
Totally agree but the major question is: Does thrombolysis by itself works in intermediate high-risk PE? From this trial, it doesn't seem so.
Farkas points out a trial I didn't know! It seems they are the same... https://emcrit.org/pulmcrit/cdt/
Is there any way we can ask our colleagues to stop this trend of standing ovations for trials? Most of the positive trials these days are incremental (and many are worse). Sure the teams should be proud of what they are doing, and I commend them for working on the trials, but it is turning out profession into a circus/clown show. Let's get back to serious science please.
I don't think the problem are the trials concept, which are a genius and probably way of proving an intervention when well done.
The problem is both trials poorly designed and a medical community with apparently no will of aspiring to know the truth by lacking the spirit of systematically critically appraising the trials.
Medicine really needs you and your careful and honest evaluation when industry and over enthusiastic investigators are so keen to ignore the real facts and just sell a new procedure or in this case an expensive device. As with the Left atrial plugs this technique will be adopted by enthusiasts despite the lack of evidence - again the real evidence is that it probably does more harm than good. One hopes that NICE in the U.K. will evaluate with more care and avoid giving it a licence.
Another excellent analysis of a "positive" clinical trial highly relevant to clinical practice. Thank you.