The implantable cardiac defibrillator (ICD) market may be poised to rebound from the black eye it has suffered following recalls and recent lead malfunctions, based on news from the REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) trial - intended to establish that patients with mild heart failure may benefit from cardiac resynchronization therapy (CRT).
The data fell short of meeting its primary endpoint, but its overall indications were that ICDs do benefit patients with mild heart failure, a group not currently approved for ICD implant.
That positive interpretation came from REVERSE investigator William Abraham, MD, director of the division of cardiovascular medicine at The Ohio State University Medical Center (Columbus), offered during a conference call sponsored by Bear Stearns (New York) and hosted by med-tech analyst Rick Wise.
The company initially released the data as part of a late-breaking trials session at the American College of Cardiology (Washington) annual meeting.
The study intended to establish that patients with mild heart failure may benefit from CRT, just as those with moderate or severe heart failure do. It failed to meet its primary endpoint — a heart failure clinical composite score at 12 months. And there was enough evidence that the therapy is worth pursuing for this new patient population.
And during the conference call, Abraham explained how important correct interpretation of these REVERSE trial data is to a large number of heart failure patients."There is really more positive news than negative news," said Abraham, who was an investigator for REVERSE. "From the clinical perspective, there are two ways to look at the results. The primary endpoint did not meet its pre-specified analytical plan. If you look beyond that, everything else is clinically meaningful. Patients improved."
He added, "It is a positive, statistically significant finding. It's supported by a marked reduction — 53%, in the risk of heart failure hospitalization. All remodeling parameters were improved. So we have very strong evidence that CRT in Class I and II patients promotes reverse remodeling. The heart gets smaller and stronger and many physicians associate that with improvement in heart failure."
Abraham said that the worst thing that can happen to a heart failure patient is to have a first hospitalization. If a patient's disease is that advanced, mortality chances increase dramatically.
"The current thinking is, you want to do everything you can to delay that first hospitalization," he said. "Virtually nothing else predicts such a bad outcome for heart failure patients. We're trying to treat earlier rather than waiting until those patients are hospitalized." Abraham added that he suspects the REVERSE data will influence physicians who already predisposed to place CRTs in patents with heart failure.
REVERSE results, he said, "are probably enough to recommend a Class IIa or IIb indication for CRT, suggesting it's reasonable to be considered, but not yet strong enough for a Class I indication. It will take larger trials and harder outcomes to get us to a 'must do,' rather than a 'should consider' type of recommendation.
"The Class II population is primed for some market expansion. They're already getting defibrillators. If I'm going to subject my patient to an implanted device, the incremental risk of adding a CRT, rather than just a primary prevention defibrillator, are worth it."
Off-label use poses several problems, not the least of which is reimbursement, he acknowledged: "It requires pre-authorization. We've done that and have been successful in Class II patients. But you generally have to make a case for clinical need."
Reimbursement has be "surprisingly good" with Medicare, but more challenging with third-party payers, "because they can look for any excuse to deny and view this as investigational. But REVERSE will help us. Most third-party payers will respond to peer-reviewed publication of these data but it depends on how the data are presented."