RESEARCH - Parecoxib/valdecoxib useful in selected noncardiac-surgery patients?

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Parecoxib/valdecoxib useful in selected noncardiac-surgery patients?

Rheumawire

Mar 8, 2005

Sue

Orlando, FL - The selective COX-2 inhibitor valdecoxib (Bextra, Pfizer) and

its IV prodrug parecoxib (Dynastat, Pfizer) reduce narcotic use postsurgery,

and while the drugs should not be used for cardiac-surgery patients because

of the increased risk of cardiovascular events, they would still be useful

for selected noncardiac-surgery patients, the lead author of 1 of the

studies of these drugs said today.

Dr Whelton ( Hopkins University School of Medicine, Baltimore,

MD) presented data from 2 studies with the drugs1 in CABG patients and 1 in

noncardiac-surgery patientsat the late-breaking clinical-trials session at

the American College of Cardiology 2005 Scientific Sessions. The studies

were funded by Pfizer. Safety data from the CABG study were published online

in the New England Journal of Medicine last month1 of 3 papers highlighting

the cardiovascular safety issues of the coxibs, which were released ahead of

print to coincide with the FDA meeting on the subject.

Whelton told rheumawire that safety and efficacy data from both the CABG and

general-surgery studies were submitted together to the Journal but that the

journal chose to publish only the safety data from the CABG trial, which

showed an increase in cardiovascular events with the drugs. " We actually

showed some benefits of the drugs in both trials, such as reduced narcotic

use, and while I am not advocating that these drugs be used in

cardiac-surgery patients, I do not believe that you should look at risk

without benefit. It would have been more appropriate to publish both the

safety and efficacy results together. Not doing so does a disservice to

patients on coxibs, " he said.

The noncardiac-surgery study did not show any increased risk of

cardiovascular events with the drugs, and while Whelton admits that this

does not rule out the possibility of such events, he says the reduced

narcotic use seen with these drugs is very useful, and, as traditional

nonsteroidal anti-inflammatory drugs (NSAIDs) are not recommended straight

after surgery because of bleeding concerns, he believes the coxibs have a

place for certain noncardiac-surgery patients. He gave as an example a

patient who has been in a traffic accident and has a head injury. " You don't

want to give narcotics if there is a concern about brain damage, and a

normal NSAID would not be recommended because of the risk of a brain

hemorrhage. The intravenous parecoxib could be suitable here. " He added that

inadequate postoperative pain control is 1 of the most important factors in

prolonging hospitalization and that opioids had their own complications such

as nausea/vomiting and ventilatory depression.

CABG study

The CABG study presented by Whelton involved 1671 CABG patients who were

randomized to 1 of 3 arms:

Parecoxib 40-mg IV loading dose, then 20 mg IV bid for 3 days,

followed by 1 week of oral valdecoxib 20 mg bid.

Placebo IV for 3 days followed by 1 week of oral valdecoxib 20 mg bid.

Placebo throughout.

All groups could have standard painkillers (morphine and

acetaminophen/codeine) as required.

Safety results showed that cardiovascular events were significantly

increased in the parecoxib/valdecoxib group and there was a trend toward an

increase in the valdecoxib-alone group.

General-surgery study

The general-surgery study involved 1062 patients undergoing noncardiac

surgery who were randomized to either parecoxib and valdecoxib (at the same

dosage regimen as in group 1 of the CABG trial) or placebo. Again, all

patients could have standard painkillers as required. Safety results showed

no difference in cardiovascular events (1% in both groups), and efficacy

results showed a similar reduction in narcotic consumption as seen in the

CABG trial with the coxibs.

" House of cards "

Discussing the studies at the late-breaking clinical-trial session, Dr

Topol (Cleveland Clinic, OH) noted that the CABG data added to the " house of

cards " that was the coxibs. He pointed out that this is not the only CABG

trial to have shown an increased risk of cardiac events with the coxibs and

that this risk occurred despite the use of aspirin. " Aspirin is not

protective against these events, " he said. He also noted that the risk of

stroke/MI was still increased in the CABG trial after the drugs were

discontinued and that there was no reduction in GI events with the drugs and

a suggestion of increased sternal wound complications. On Whelton's

presentation, Topol commented to rheumawire: " My concern is that he didn't

present the fact that sternal wound infections were worsened, that GI

complications weren't avoided, and that the warning should extend far beyond

the open-heart CABG story to all patients at risk of having documented

coronary disease. "

Delayed wound healing?

On the issue of sternal complications, Whelton told rheumawire that a

previous smaller study in CABG patients (by Ott et al) had shown a

significant increase in sternal wound complications with coxibs, so they

specifically looked for this in these studies. While there was a trend

toward delayed wound healing with the drugs, this did not reach

significance. Whelton said that he was expecting to see a greater effect, as

there was a biological explanationcoxibs inhibit inflammation, which is

needed in wound healing. " I thought we would see a significant effect, as it

would fit with the biology, but I think we can say that if there is a

problem with wound healing it is only a mild problem, " he commented.

Not an MD

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org