Vioxx increases CV events in arthritis patients with high BP

[Guest guest]

Rheumawire

Mar 19, 2004

Rofecoxib increases CV events in arthritis patients with high BP

New Orleans, LA - A new analysis has shown that hypertensive arthritis

patients using the COX-2 inhibitor rofecoxib (Vioxx®, Merck & Co) double

their risk of cardiovascular events.

The other main COX-2 inhibitor, celecoxib (Celebrex®, Pfizer), or other

nonspecific nonsteroidal anti-inflammatory drugs (NSAIDs) did not appear

to increase this risk of cardiovascular events, Dr Whelton

(Universal Clinical Research Center Inc, Hunt Valley, MD) told the

American College of Cardiology 2004 Scientific Sessions last week.

The findings are based on a study funded by Pfizer, which markets

Celebrex, and used a large New England healthcare claims database

containing information on more than three million individuals. Whelton

et al selected a sample of approximately 34 000 patients with

osteoarthritis or rheumatoid arthritis. They were then divided into

normotensive patients and those being treated for hypertension.

The researchers looked at whether additional therapy with a variety of

drugs for arthritis would increase the risk of MI or stroke.

Those taking rofecoxib had more than double the risk of these events

(relative risk 2.45; p<0.0001 vs non-NSAID users). Comparable figures

for those taking celecoxib were 1.35 (p=0.06 vs non-NSAID users) and

1.11 for nonspecific NSAID users (p=0.4 vs non-NSAID users). The p value

for the difference between risk of cardiovascular events among rofecoxib

users compared with celecoxib users was 0.004.

When asked in a press conference why this effect was seen with one COX-2

inhibitor and not the other, Whelton said he believed this to be an

effect within the cell itself and not related to the systemic effects on

inflammation.

He added that while he is not yet willing to make treatment

recommendations, " practitioners need to be cognizant of the fact that

when treating hypertensive patients, the coxibs destabilize blood

pressure. "

Merck & Co, which markets rofecoxib, told Reuters Health that these

findings are based on a claims database, so it is difficult to tell

whether the drug prescribed was actually taken. Also, it's possible that

the cardiac events referred to took place before the index drug was

taken. Finally, this was an observational study, not a randomized trial,

the company notes.

In 2002, Merck was required to add a warning to the US label of Vioxx to

reflect the findings of the VIGOR study, which showed an elevated risk

of cardiovascular events with rofecoxib compared with naproxen. Merck

has always maintained, however, that this was due to a protective effect

of naproxen rather than a prothrombotic effect of rofecoxib; the debate

has been rumbling on for some time and has not yet been fully resolved.

Merck's follow-on COX-2 inhibitor, etoricoxib, was also 1.7 times as

likely to cause thrombotic events as naproxen in a recent meta-analysis,

reported by rheumawire.

Meanwhile, a second study, published in the March 2004 issue of

Hypertension, is " the only study to date " that has evaluated 24-hour

ambulatory blood pressure and glomerular filtration rate (GFR) in black

and Hispanic patients taking ACE inhibitors and diuretics for

hypertension and an anti-inflammatory for arthritis.[1]

Dr Munavvar Izhar (Rush Medical Center, Chicago, IL) found that both

celecoxib and diclofenac, a nonspecific NSAID, dampened the hypertensive

effects of ACE inhibitors and diuretics. Diclofenac also adversely

affected renal function.

Using a crossover design, they examined the effects of celecoxib (200

mg/day) and diclofenac (75 mg twice daily) on BP and renal function in

25 patients, all of whom were black or Hispanic. At four weeks,

diclofenac worsened overall 24-hour systolic BP control (+4.1 mm Hg)

significantly more than celecoxib (+0.6 mm Hg) in the presence of an ACE

inhibitor and diuretic. However, at peak drug levels, diclofenac and

celecoxib had similar effects on systolic BP (+3.6 and +4.2 mm Hg,

respectively).

Thus, if celecoxib is needed twice daily, as is frequently the case, " a

rise in BP of similar magnitude to diclofenac would be anticipated, "

they point out.

With regard to GFR, diclofenac significantly reduced this, which was

associated with marked urinary sodium retention, which led to ankle

edema, despite diuretic therapy. Celecoxib, on the other hand, preserved

GFR and was not associated with urinary sodium retention or ankle

swelling.

While the doctors recognize the limitations of their small study, they

say: " Physicians need to be alerted to these effects on BP and kidney

function and to monitor BP accordingly in all patients receiving agents

that inhibit the cyclooxygenase enzyme system. "

Nainggolan

Source

1. Izhar M, Alausa T, Folker A, Hung E, Bakris GL. Effects of COX

inhibition on blood pressure and kidney function in ACE

inhibitor-treated blacks and hispanics. Hypertension 2004 Mar;

43(3):573-7.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org