The implantable cardiac defibrillator (ICD) market may be poised to rebound from the black eye it suffered following lead malfunctions and recalls, based on news from the REVERSE trial intended to establish that patients with mild heart failure may benefit from cardiac resynchronization therapy (CRT) which failed to meet its primary endpoint but provided proof that ICDs do benefit patients with mild heart failure.

ICDs are not currently FDA-approved for these patients.

That's the opinion of a REVERSE investigator, who also is an internationally known researcher in ICD therapy and heart failure, as relayed during a conference call sponsored by Bear Stearns (New York) and hosted by med-tech analyst Rick Wise.

Last fall Medtronic (Minneapolis) pulled its Fidelis family of ICD leads thin wires connecting the defibrillator to the heart because they may break inside the body (Medical Device Daily, Oct. 16, 2007).

This week, the company released data on a 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. But there is enough evidence that the therapy is worth pursuing for this new patient population.

Data from the REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) clinical trial were presented as part of the late-breaking sessions at the American College of Cardiology (Washington) annual meeting in Chicago earlier this week (Medical Device Daily, April 3, 2008).

During the conference call, William Abraham, MD, director of the division of cardiovascular medicine at Ohio State University Medical Center (Columbus), 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 in the REVERSE trial. "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 said he suspects the REVERSE data will influence physicians who are already predisposed to place CRTs in patents with heart failure.

"The results of REVERSE 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," he said. "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."

This off-label use poses several problems, not the least of which is reimbursement. "It requires pre-authorization," Abraham said. "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."

Despite the good news of better options for more heart failure patients, Abraham said that up to 70% of this patient population still is being managed by the primary care community and advances such as these take years to trickle down.

"But we're actually seeing referral rates for implantations start to go up again," he said. "Over the next 12 to 24 months we'll see 5% to 10% growth rates by getting this message further out to cardiologists and the general medical community. But I don't think we'll jump to double digit growth rates until 2010, when we expand the indication and this educational information gets to primary care physicians."

Will the positive side of REVERSE erase the bad publicity surrounding CRT devices in general?

"There was a string of problems with a number of devices and leads that shook our confidence a little bit," Abraham said. Despite those reported problems, he said the overall efficacy rate for defibrillators is 97% to 98% in the heart failure population. "There's nothing else that is that good," he said.

"During the fourth quarter of 2007, the U.S. ICD market rebounded a bit to 4% growth after six quarters of being flat-to-down due to slowing referral patterns and product recalls," Wise said. "We currently project mid-to-high single-digit U.S. ICD market growth through the end of the decade."

The Centers for Disease Control and Prevention (Atlanta) reports that about 5 million people in the U.S. have heart failure and there are more than 1 million hospitalizations per year. It's the most common reason for hospitalization among people on Medicare.