Daily Vioxx ® Can Cause Spike
in Blood Pressure for Those with Diabetes
Vioxx treatment increased blood pressure
in patients who had the combination of diabetes,
hypertension, and osteoarthritis.
In contrast, treatment with two other NSAIDs,
celecoxib and naproxen, led to no boost in blood
pressure, Dr. James R. Sowers said at the annual
meeting of the American College of Cardiology.
In a controlled study with more than 400 patients,
the average increase of 4.2 mm Hg in 24-hour,
systolic pressure triggered by regular treatment
with rofecoxib, is “possibly clinically
significant,” said Dr. Sowers, chief of
the division of endocrinology, diabetes, and hypertension
at the State University of New York, Brooklyn.
“The larger increase in systolic blood
pressure caused by rofecoxib [compared with celecoxib
or naproxen] may reflect the relatively greater
effect of rofecoxib on the COX-2 [cyclooxygenase-2]
enzyme in the kidney and vasculature,” Dr.
Sowers said. “Rofecoxib may be a more specific
COX-2 inhibitor, and the COX-2 enzyme is very
important for producing prostacyclin in the kidney
and vasculature.”
The study enrolled patients aged 40 or older
who had diabetes, hypertension, and osteoarthritis
of the hip or knee. Patients also had to be treated
with an angiotensin-active drug for hypertension.
Most patients were on an ACE inhibitor, and the
remaining patients were treated with an angiotensin-receptor
blocker.
Patients were “washed out” of their
entry treatments for osteoarthritis by discontinuing
those drugs and treating them with acetaminophen
only for a short period. They were then randomized
to treatment with 200 mg/day celecoxib, 25 mg/day
rofecoxib, or 500 mg b.i.d of naproxen. These
dosages are considered to have comparable efficacy
for osteoarthritis, Dr. Sowers said.
After 6 weeks of treatment, the 138 patients
treated with rofecoxib had an average increase
in their systolic blood pressure of 4.2 mm Hg
as measured by a 24-hour blood pressure monitor,
a statistically significant increase. The increased
pressure was maintained through 12 weeks of treatment.
Treatment with rofecoxib also led to significant
increases in pulse pressure at weeks 6 and 12,
and was associated with a trend toward increased
edema and weight gain. None of these changes were
seen among the 136 patients treated with celecoxib
or the 130 patients treated with naproxen.
In a separate poster presented at the same meeting,
researchers from Merck reported no significant
change in either systolic or diastolic blood pressure
among patients with osteoarthritis treated with
12.5 mg/day rofecoxib, 25 mg/day rofecoxib, 200
mg/day celecoxib, or 4,000 mg/day acetaminophen.
This analysis combined data from two separate
efficacy studies with a total of 1,960 patients.
The primary end point of these studies was patient
global assessment of response to therapy. Both
studies included all patients with osteoarthritis
without specifically targeting patients with diabetes
and hypertension.
The results also showed that the 12.5-mg/day
dosage of rofecoxib and the 200-mg/day dosage
of celecoxib had similar efficacy for controlling
symptoms of osteoarthritis. The 25-mg/day dosage
of rofecoxib led to significantly greater improvement
in osteoarthritis symptoms.
