APPRAISE ATP Highlights the Trade-offs of Antitachycardia Pacing

In patients with implantable cardioverter-defibrillators (ICDs) for the primary prevention of sudden cardiac death, programming the devices to deliver a single burst of antitachycardia pacing (ATP) as a first approach lengthens the time to a first all-cause shock compared with a shock-only approach, according to the results of the APPRAISE ATP trial.

There was an absolute reduction in the risk of all-cause shock of about 1% per year, but that advantage didn’t come without a cost. The risk of ventricular tachycardia/ventricular fibrillation (VT/VF) storm—three or more episodes requiring therapy in 24 hours—throughout follow-up was twice as high with the ATP-first approach, contributing to the lack of a difference in total shock burden between trial arms.

The results, published online recently in JAMA, “should be considered during shared decision-making in the selection of ICD hardware in primary prevention cohorts,” lead author Claudio Schuger, MD (University of Rochester Medical Center, NY), and colleagues say.

Indeed, the results add a layer of complexity to discussions with patients about whether they should receive an ICD and, if so, which device they should get, said Paul Varosy, MD (University of Colorado School of Medicine and Rocky Mountain Regional VA Medical Center, Aurora), who provided his personal perspective to TCTMD and was not speaking for either of his institutions.

“The key findings of this trial imply that we need to add how the device is programmed to the shared decision-making conversations that we have with patients about ICD therapy. It’s not just whether the patient wants an ICD. We really do need to talk about how to program the device as well,” commented Varosy, who wrote an accompanying editorial with Amneet Sandhu, MD (University of Colorado School of Medicine and Rocky Mountain Regional VA Medical Center), and Daniel Matlock, MD (University of Colorado School of Medicine, Aurora, and VA Eastern Colorado Geriatric Research Education and Clinical Center, Denver).

Varosy highlighted the trade-offs involved for patients. “If they choose to go with shocks only, they may have a more unpleasant shock therapy as their first therapy from the device,” he explained. “If they go with antitachycardia pacing first, there's a pretty good chance that it may disrupt the arrhythmia painlessly, but it also increases the risk of them stirring up multiple shocks down the road. That conversation is challenging, but it’s clearly an important one that we'll need to have with patients moving forward.”

APPRAISE ATP Trial

Though ATP is commonly used in current practice as a way to painlessly terminate VTs without the need for a shock, prior assessments of the approach came before the advent of newer ICD technologies, like subcutaneous and extravascular devices, and before updated programming guidelines aimed at reducing premature and inappropriate shocks.

“We needed to define, in an era of new programming with longer delays and new platforms of implantation, the value of ATP,” Schuger told TCTMD.

APPRAISE ATP, conducted at 134 sites in eight countries in North America, Europe, and Asia, included 2,595 patients (mean age 63.9 years; 22.4% women) who had a class I or IIA indication for a primary prevention ICD and an LVEF of 35% or less. All underwent implantation of a Boston Scientific single- or dual-chamber ICD and were then randomized to an ATP-first or shock-only strategy, with device programming aligned with guidelines from the Heart Rhythm Society.

The trial was designed to test the equivalence of the two strategies, with a relative margin of 35%. Superiority testing was performed at interim and final analyses if equivalence was not proven.

The primary endpoint was the time to first all-cause shock, and through a mean follow-up of 38 months, risk was reduced in the ATP-first arm (HR 0.72; 95.9% CI 0.57-0.92). The analysis excluded equivalence between the two strategies, and indeed, the ATP-first strategy was shown to be superior (P = 0.005). Findings were similar across subgroups, including those defined by etiology (ischemic or nonischemic), history of atrial fibrillation, age, and sex.

ATP prolonged the time to both first appropriate and first inappropriate shocks, with the difference in appropriate shocks driven by a reduction in monomorphic VT; it had no significant impact on polymorphic VT or VF.

During the study, however, total shock burden was not significantly different between the ATP-first and shock-only arms (12.3 vs 14.9 per 100 patient-years; P = 0.70). That was in part due to a greater risk of VT/VF storm when considering first and subsequent events in the ATP-first group (HR 2.26; 95% CI 1.18-4.30).

There were no significant between-group differences in risks of all-cause death (HR 1.15; 95% CI 0.94-1.41) or of a composite of all-cause death or time to first all-cause shock (HR 0.92; 95% CI 0.78-1.07).

Complexity of ICD Decisions

ICDs have been shown to reduce mortality in appropriately selected patients. However, they require both a surgical procedure for implantation and the willingness to potentially receive lifesaving, but painful, shocks.

“I live here in the Mountain West where many of my patients can say from firsthand experience that an ICD shock feels like being kicked by the hind legs of a horse. It's a real jolt to be shocked by a device,” Varosy said. “As such, avoiding shocks is a good thing, but if a shock occurs, the hope is that it was necessary to prevent a patient from dying from a life-threatening ventricular arrhythmia, rather than a shock delivered inappropriately or unnecessarily.”

Integrating a discussion of ATP and device programming into the decision-making process adds another set of trade-offs, with no well-defined, right-or-wrong choice.

“At its core, shared decision-making is having the patient understand what they're getting into in terms of the risks and benefits of the treatment, having us understand what the patient's goals and values are, and then the patient coming to a well-informed, autonomous decision with the support of a doctor who understands the patient’s values,” Varosy said.

Consideration of ATP also may influence which type of ICD a patient receives because there are now multiple options to choose from—ie, transvenous systems, subcutaneous devices, and extravascular devices—and not all can deliver antitachycardia pacing, he noted, adding that the situation is going to get even more complex in the coming years.

Schuger pointed out that the APPRAISE ATP results indicate that antitachycardia pacing is not as effective at terminating ventricular arrhythmias as indicated by prior trials. ATP terminated the arrhythmias in 54% of cases in the current trial, much lower than the 81% rate observed with a single ATP burst in PainFREE Rx II, which was published two decades ago.

“This presents the physicians and the patients with new parameters to decide” which type of ICD they’d like to use, he said, also highlighting the absolute reduction in all-cause shocks with ATP of about 1% per year.

That “makes clear to me” that the best choice of ICD after going through the shared decision-making process is the one that comes with a lower risk of side effects, Schuger said.