Non-significant Studies Can Teach A Lot

One-year results of the SWISS-APERO study of two left atrial appendage closure devices reveal similar but very sobering results

Many doctors believe that closing the left atrial appendage (with a device) will help reduce stroke and bleeding.

The idea behind stroke reduction is that occluding the appendage takes away a common area where clots form. The reason for less bleeding is that patients with proper occlusion can often be taken off anticoagulant drugs.

These are nice ideas. Cardiac surgeons have shown in the LAAOS III trial that surgical closure of the appendage (different than plugging it from the inside) reduced stroke. Importantly, in LAAOS III, patients remained on anticoagulant therapy.

When a surgeon closes the appendage, the closure is likely to be complete (they cut it off and then sew the atrium together) and there is no foreign body left in the atrium.

When cardiologists close the appendage, they do so with a plug that should fit snugly into the appendage. There should be no leaks of blood around the device into the appendage—because these leaks can actually increase the risk of clots.

Today I will tell you about one-year results of the SWISS-APERO trial—which compared outcomes with the two most common types of closure devices.

The original SWISS APERO trial results came in 2021. The authors reported that the devices performed similarly, though there were some technical nuances between the devices. This study report included only 45-day outcomes.

The most recent report included 13-month performance data.

They main outcome measure was patency of the left atrial appendage. Pause there. This is a decidedly bad outcome. You don’t want the appendage to be patent. You want it to be occluded. You’d like these percentages to be low.

If the appendage is “patent” this means there is blood getting into the appendage around the device. I’ve already told you that peri-device leaks are associated with an increase in stroke risk.

The Main Result:

Patency was observed in 54% of patients with one device and 49% with the other device.

The authors emphasized that there were no statistical differences between the two devices.

Conclusions/Comments

This is a devastating result for proponents of percutaneous LAA occlusion.

It shows that with the two most commonly used devices, proper occlusion occurs in only half the patients. Keep in mind also that this poor performance occurred in a trial with skilled investigators who are likely proponents of the device. In other words: a best case scenario.

I have long been critical of this technique. I have argued, along with Andrew Foy and Gerald Naccarelli, that that seminal trials reveal no signal for benefit. We have failed to persuade our colleagues, as LAAO has become a popular technique.

In news coverage of the trial, one of the top experts and proponents for appendage closure, Dr. Vivek Reddy, called these results disappointing and depressing because there were so many leaks.

Proponents of the device argue that SWISS APERO results may not be that bad—because the trialists measured patency of the appendage with highly-sensitive CT scans. The more typical way to evaluate for leaks is with echocardiography (ultrasound).

Reddy, however, seemed unconvinced:

Addressing the question of the best tools for evaluating leak, Reddy suggested that it might not matter whether it’s assessed using TEE or CT.

Final Conclusion:

I highlight this study because it provides two lessons.

One is that directly comparing two therapies in randomized fashion can teach us a lot about performance. Most therapies gain approval by being compared against standard of care or a placebo. (An example are the four direct acting anticoagulants, which gained approval from trials comparing each agent against warfarin. We have no direct head-to-head comparisons between agents. Trials like that would be helpful.)

The second reason to highlight SWISS APERO is that it surprised us in showing that neither device performed well. The idea that a procedure with occlusion in its name (left atrial appendage occlusion or LAAO) failed to completely occlude the appendage about half the time is worrisome.

One of the main reasons we argued—initially— against the stroke-prevention procedure was that ischemic strokes (those caused by clots) were actually higher in the device arm in the original trials.

That we now have data (about 10 years later) showing that the most up-to-date devices fail to occlude the appendage in half the patients provides a plausible reason why ischemic strokes were higher in the seminal device-vs-warfarin trials.

This new data supports my extreme skepticism about this preventive procedure. Yet I remain an outlier.

As always, we are open to opposing arguments.

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