TOTAL: Opening eyes but not shutting doors

The major scientific meetings often bill their late-breaking clinical trials as potentially practice-changing revelations. They certainly add insight, even when questions linger.

The American College of Cardiology wrapped up a three-day scientific session on March 16 that featured 22 late breakers. The topics reflected the diversity of cardiovascular subspecialties, with interventional cardiology getting its due, especially on the closing day. TOTAL (The Trial of Routine Aspiration Thrombectomy with PCI versus PCI Alone in Patients with STEMI) was noteworthy because it did not evaluate new vs. standard care, but rather routine vs. standard care.

The routine in this case was manual thrombectomy. The trial’s presenter, Sanjit Jolly, MD, of McMaster University in Hamilton, Ontario, estimated at a press conference that 20 percent of interventional cardiologists in the U.S. and 30 percent of operators worldwide routinely use thrombectomy to remove thrombus during PCIs.

“A lot of interventionalists do thrombectomy because it makes their case easier to do,” Ajay Kirtane, MD, SM, of the Center for Interventional Vascular Therapy and chief academic officer at Columbia University Medical Center in New York City, said in an interview. Kirtane was not involved in the study, but as co-director of the Transcatheter Cardiovascular Therapeutics meeting and a Cardiovascular Research Foundation faculty member, he is well aware of the unknowns in interventional cardiology.  

“Unfortunately, a case that is easier to do is not an endpoint that is often measured in clinical trials,” he said. “But yet you would like to see if there was some other benefit to thrombectomy, besides making your case easier.”

The trial defined its primary endpoint as death from cardiovascular causes, recurrent MI, cardiogenic shock or New York Heart Association class IV heart failure at 180 days. The safety endpoint was stroke at 180 days. Patients treated with thrombectomy plus PCI and PCI alone had similar primary outcomes (a rate of 6.9 percent with thrombectomy and 7 percent with PCI alone) but the 30-day and 180-day stroke rate was higher in the thrombectomy group.

Stroke events were relatively rare: the rate was 0.7 percent for thrombectomy vs. 0.3 percent with PCI alone at 30 days and 1 percent and 0.5 percent at 180 days. Discussant David Kandzari, MD, of the Piedmont Heart Institute in Atlanta, pointed out that in the 7 percent of patients who needed thrombectomy bailout, in an as-treated analysis the early stroke rate was not significantly different.

The results raise question about stroke that will be investigated further by the TOTAL researchers. In the meantime, interventional cardiologists likely will continue to use thrombectomy selectively, despite no clinical benefit, “unless there is a safety hazard,” according to Kandzari.

Kirtane also saw changes in practice likely pivoting on the stroke question. “We need to find out more about [stroke] before we can say there is increased harm,” he said. “If it makes your case easier but it harms the patient, then you shouldn’t do it. If it makes your case easier and there is no harm associated with it, [then] that makes a case for selected use.”

The clinical need remains, whether treatment involves manual thrombectomy or not. “We still have a subset of patients who do very poorly with heavy thrombus burden,” Jolly said. “This area of investigation is certainly not dead. We need to pursue other strategies to improve these patient outcomes. Is it pharmacologic? Is it other devices? I don’t know but I think we need to continue searching for an answer.”