What's Hot in Clots: April 2026

The spring is finally here—usually the happiest time of the year for me. This time it’s different…I’m holding onto hope that by the next time I write to you, the world will feel a little more peaceful.

Choice of DOACs for acute treatment of VTE: We have a clear winner!

For years, some people used apixaban and rivaroxaban interchangeably for acute treatment of VTE. Some insurance companies preferred to cover one vs another for cost decisions. And yet, several clinicians—based on indirect comparisons or observational comparative safety studies—had a hunch that apixaban might be the safer of the two. Guess what? They were right!! 

In the COBRRA trial, acute treatment with apixaban, compared with rivaroxaban, resulted in a clinically meaningful and statistically significant reduction in clinically relevant bleeding events, including major bleeds. Recurrent VTE was rare and comparable. Read more.

Antiphospholipid antibodies and thrombosis: Rare no more!

When I was a medical student and resident, the classic teaching was that thrombotic antiphospholipid syndrome is rare and diagnosed only when there is persistent seropositivity for antiphospholipid antibodies (aPL) and a thrombotic event. Through a 3-year effort, we shattered those thoughts and provided a systematic summary of the prevalence and clinical relevance of aPL across a wide spectrum of patients with and without known thrombosis. 

The bottom line: Even single-time seropositivity carries risk but there is a gradient. The higher the titers, the greater the number of positive antibodies—and the longer they stay positive, the greater the risk. Read more here on the pathophysiology and clinical relevance.

Catheter-directed fibrinolysis in intermediate-high risk pulmonary embolism: A win? Not a win? Or it’s complicated?

At ACC 2026, the results of the long-awaited HI-PEITHO trial came out. On a first look, the trial met its primary outcome with a lower risk of clinical deterioration. And kudos to the trialists for completing the largest trial to date in this patient population! So, colleagues who call it a win have a point. 

However, there was no significant difference in PE-related death (3 in the catheter-directed fibrinolysis group compared with 1 in the anticoagulation monotherapy group) and the “deterioration” component was largely driven by differences in the NEWS score rather than hemodynamic collapse. There was also a numerically greater number of major bleeding events with fibrinolysis, although there were no intracranial or fatal bleeding events.  Only 10% of patients in the control arm had PE death or underwent rescue therapy. So, one can also argue that we can watch these patients closely and only for the small minority who deteriorate, rescue therapy can be considered. If I were to summarize, I’d say it’s complicated! Read more and see the accompanying editorial here.

Left atrial appendage closure vs anticoagulation in AF: Not-non-inferior? Non-inferior? Non-not-non-inferior???

Okay, maybe I confused you, but believe me when I say that it’s not just me! I’ve had a longstanding interest in noninferiority design for clinical trials. It’s a very helpful design in certain cases, including here, but much more complex to analyze and interpret. Some biases that will lead to “neutral” or “inconclusive” results in a traditional superiority trial (e.g., lower than an expected event rate) may, in fact, bias a trial toward claiming non-inferiority. 

In this context, I can share with you that CLOSURE-AF (which to me was designed and reported more rigorously) failed to show noninferiority while CHAMPION-AF called noninferiority. However, the latter occurred on the backdrop of lower-than-expected event rates and an absolute non-inferiority margin (see my comments about potential flaws with noninferiority design). Also, if you look carefully in the CHAMPION-AF supplement, ischemic stroke seemed to occur more frequently with left atrial appendage closure than with anticoagulation. 

The bottom line: I wouldn’t consider left atrial appendage closure as first-line therapy in most of my patients.