Medical Device Daily

ORLANDO, Florida – Drug/device combinations clearly are beneficial, as shown in the exploding drug-eluting stent (DES) market.

And the exploration of drugs and devices in cardiovascular therapeutics, used separately but in a careful, contiguous regimen, also was explored in a late-breaking trials presentation Monday morning during the American College of Cardiology's (Bethesda, Maryland) annual meeting at the increasingly bustling Orange County Convention Center.

The (not unexpected) conclusion: Sometimes such strategies work, sometimes they don't, and sometimes device treatments work when drug therapies fail – with the ACC presentations helping cardiologists know, it is hoped, how to choose the correct combination of strategies.

One of the most promising of these reports was made by Stuart Connolly, MD, director of the arrhythmia service and electrophysiology lab at McMaster University (Hamilton, Ontario), who reported on the use of an anti-arrhythmic medication, amiodarone, to improve the "tolerability" of implantable cardioverter-defibrillators (ICDs), specifically the pain caused by the shocks these devices deliver.

Connolly noted the considerable pain produced when 700 volts of energy are deployed in a patient's chest. This can be "upsetting," he said, and while many patients simply tolerate the pain, some may ask that the devices be removed.

In the Optimal Pharmacological Therapy in Implantable Cardioverter Defibrillator Patients (OPTIC) trial, 412 patients implanted with a dual-chamber ICD from St. Jude Medical (St. Paul, Minnesota) were randomized to either beta blockers alone, to sotalol alone or to amiodarone plus a beta blocker.

Those patients who received the amiodarone combination saw the frequency of shock drop to 10% annually as compared to 24% for those who received sotalol and to 39% who received a beta blocker alone.

Connolly noted that some of these drugs, or combinations of them, are prescribed to patients after they complain of frequent inappropriate shocks, but that this study focused on giving them shortly after implantation as a preventive strategy.

"We're actually looking at preventing shocks from occurring in the first place," he said, acknowledging a considerable irony, since the devices are implanted to produce shocks.

"This study shows shocks are very common in these patients, and that amiodarone is really effective in reducing their number," Connolly said. And he concluded: "the results represent a huge reduction in shocks and a big improvement in quality of life."

Connolly was peppered with questions in the Q&A part of the presentation concerning issues of safety.

While he acknowledged that the drug had some side effects, he ruled it "safe." He called the side effects "real – but we've been managing them for years." The key, he said, was the physician's patient consultation and management of the risks.

He also said that there had been no evidence that the drug suppressed those shocks that were actually needed to sustain the patient's life.

He said there had been "a lot of cardiac arrests" reported in the 400-patient trial but only two deaths.

The ICDs had received "aggressive programming" for anti-tachycardia pacing, he noted, and added that future studies might suggest "perhaps a more aggressive approach."

Asked if his specific recommendation was to use the drug therapy along with ICD implantation, he said: "My inclination is to do so."

Also at ACC, in two parallel studies providing opposite results, researchers reported that the use of an analgesic should not be used after a coronary artery bypass grafting (CABG) procedure but is safe and provides good pain relief following general surgery.

The two trials were conducted in patients undergoing CABG and patients undergoing general surgery. CABG patients were randomized to three days of intravenous parecoxib followed by seven days of valdecoxib, the oral form of parecoxib, or to three days intravenous placeo followed by seven days of oral placebo.

All patients were followed for 30 days for the occurrence of adverse events.

In the CABG trial, cardiovascular adverse events were significantly greater in patients who received parecoxib followed by oral valdecoxib, compared to patients who received intravenous and oral placebo.

However, the parecoxib significantly reduced patient need for post-operative narcotic analgesia, according to Andrew Whelton, MD, who presented the findings. Whelton is director of the Universal Clinical Research Center and adjunct professor of medicine at the Johns Hopkins University School of Medicine (Baltimore).

While he acknowledged that the general surgery trial was not "powered" to the CABG trail with respect to cardiovascular outcomes, results were in contrast to those found in CABG patients. Patients who received parecoxib required significantly less morphine than patients who received standard care and they also reported significantly better post-operative analgesia, Whelton reported.

"We conclude that parecoxib/valdecoxib should not be used in high-risk patients undergoing cardiovascular surgery. However, in general surgery, the drug looks fine, and in fact, has certain advantages as an analgesic," he said.

Whelton acknowledged that the studies were funded by Pfizer (New York), the manufacturers of the drugs used in the trials, adding, "If they don't fund it, [these studies] just don't get done."

As for particular recommendations concerning future clinical procedure, he said he would "defer any directions to the general prescribing public," and that with further study there will be "a full balance of all extant data, of the risks and benefits."