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Ibuprofen Is Associated with a Rise in Blood
Pressure in Patients with Arthritis and
Cardiovascular Risk – PRECISION-ABPM Trial
In patients with osteoarthritis or rheumatoid arthritis,
ibuprofen was associated with increased blood
pressure and hypertension compared with celecoxib
as well as an increased risk of cardiovascular
disease. This conclusion, based on results of the
double-blind noninferiority cardiovascular safety
trial called Prospective Randomized Evaluation of
Celecoxib Integrated Safety vs Ibuprofen or Naproxen
Ambulatory Blood Pressure Measurement (PRECISION-
ABPM), was presented at the 2017 European Society
of Cardiology (ESC) Congress, from August 26–30.
F
rank Ruschitzka, MD, of the
University Heart Centre, Zurich,
Switzerland, explained that
nonsteroidal anti-inflammatory drugs
(NSAIDs), both nonselective and selective
cyclooxygenase-2 (COX-2) inhibitors, are
among the most widely prescribed drugs
worldwide, though they are linked with
increased blood pressure and adverse
cardiovascular events.
One-fourth of the world’s population aged
over 35 years has arthritis, and of these,
almost half have or are at high risk of
cardiovascular disease, particularly hyper-
tension,” Dr. Ruschitzka said during his
presentation. “Clinicians need to weigh
the potential hazards of worsening blood
pressure control and its clinical sequelae
against the arthritis-mitigating benefits
associated with the use of NSAIDs, par-
ticularly ibuprofen.
The landmark PRECISION study was a
prospective, long-term noninferiority trial
of 24,081 patients. It was designed to
assess the cardiovascular safety of cel-
ecoxib vs prescription-strength doses of
ibuprofen and naproxen in patients with
chronic pain from osteoarthritis or rheu-
matoid arthritis.
It was conducted at 60 sites in the US and
included 444 patients, of whom 408 (92%)
had osteoarthritis and 36 (8%) had rheu-
matoid arthritis. All patients had evidence
of, or were at increased risk for, coronary
artery disease.
PRECISION-ABPM, a prespecified
4-month substudy of the PRECISION
trial, was designed to determine the
blood pressure effects of the selective
COX-2 inhibitor celecoxib compared to
the non-selective NSAIDs naproxen and
ibuprofen.
Patients were randomized 1:1:1 to
celecoxib (100–200 mg twice a day), ibu-
profen (600–800 mg three times a day),
or naproxen (375–500 mg twice a day)
or placebo. The primary endpoint was
change from baseline in 24-h ambulatory
blood pressure after 4 months.
Celecoxib decreased average systolic
blood pressure measured over 24 h by
–0.3 mmHg. Ibuprofen and naproxen
increased it by 3.7 and 1.6 mm Hg,
respectively. The resulting difference of
–3.9 mmHg between celecoxib and ibu-
profen was significant (P = .009).
According to Dr. Ruschitzka the
PRECISION-ABPM showed differential
blood pressure effects between the dif-
ferent NSAIDs, ibuprofen and naproxen,
and the COX-2 inhibitor celecoxib. While
celecoxib and naproxen produced either
a slight decrease (celecoxib) or a rela-
tively small increase (naproxen) in blood
pressure, ibuprofen was associated with a
significant increase in ambulatory systolic
blood pressure of more than 3 mmHg.
An additional analysis showed that the
percentage of patients with normal
baseline blood pressure who developed
hypertension (n=5) was 23.2% for ibu-
profen, 19.0% for naproxen, and 10.3% for
celecoxib (odds ratio 0.39, P = .004; and
0.49, P = .03 for celecoxib vs ibuprofen
and naproxen, respectively).
“Patients receiving ibuprofen experienced
a 61% higher incidence of de novo hyper-
tension vs those receiving celecoxib,”
Dr. Ruschitzka said.
The results supported and extended the
findings of the PRECISION trial, inasmuch
as they demonstrated noninferiority of the
primary cardiovascular outcomes with
moderate doses of celecoxib vs naproxen
or ibuprofen. The findings may hold the
greatest clinical significance in the elderly,
who suffer a high prevalence of arthritis
and hypertension.
“The findings suggested that the elevated
cardiovascular risk with NSAIDs may be
partly due to drug-specific increases in
blood pressure, challenging the widely
cited hypothesis that adverse effects of
NSAIDs relate directly to their effects
on platelets and endothelial cells,"
Dr. Ruschitzka said.
He added, “Since decreasing systolic blood
pressure by just 2 mmHg lowers stroke
mortality by 10% and ischemic heart dis-
ease mortality by 7%, increases in systolic
blood pressure associated with NSAIDs as
observed in PRECISION-ABPM should be
considered clinically relevant.”
PracticeUpdate Editorial Team
Dr. Frank Ruschitzka
PRACTICEUPDATE CONFERENCE SERIES • ESC Congress 2017
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