Acetaminophen increases blood pressure in patients with coronary artery disease.
BACKGROUND
Because traditional nonsteroidal antiinflammatory drugs are associated with increased risk for acute cardiovascular events, current guidelines recommend acetaminophen as the first-line analgesic of choice on the assumption of its greater cardiovascular safety. Data from randomized clinical trials prospectively addressing cardiovascular safety of acetaminophen, however, are still lacking, particularly in patients at increased cardiovascular risk. Hence, the aim of this study was to evaluate the safety of acetaminophen in patients with coronary artery disease.


RESULTS
The 33 patients with coronary artery disease included in this randomized, double-blind, placebo-controlled, crossover study received acetaminophen (1 g TID) on top of standard cardiovascular therapy for 2 weeks. Ambulatory blood pressure, heart rate, endothelium-dependent and -independent vasodilatation, platelet function, endothelial progenitor cells, markers of the renin-angiotensin system, inflammation, and oxidative stress were determined at baseline and after each treatment period. Treatment with acetaminophen resulted in a significant increase in mean systolic (from 122.4±11.9 to 125.3±12.0 mm Hg P=0.02 versus placebo) and diastolic (from 73.2±6.9 to 75.4±7.9 mm Hg P=0.02 versus placebo) ambulatory blood pressures. On the other hand, heart rate, endothelial function, early endothelial progenitor cells, and platelet function did not change.


CONCLUSIONS
This study demonstrates for the first time that acetaminophen induces a significant increase in ambulatory blood pressure in patients with coronary artery disease. Thus, the use of acetaminophen should be evaluated as rigorously as traditional nonsteroidal antiinflammatory drugs and cyclooxygenase-2 inhibitors, particularly in patients at increased cardiovascular risk.


BACKGROUND
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00534651.
Cardiovascular Center Cardiology University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland.
Isabella
I
Sudano
Andreas J
AJ
Flammer
Daniel
D
Périat
Frank
F
Enseleit
Matthias
M
Hermann
Mathias
M
Wolfrum
Astrid
A
Hirt
Priska
P
Kaiser
David
D
Hurlimann
Michel
M
Neidhart
Steffen
S
Gay
Johannes
J
Holzmeister
Juerg
J
Nussberger
Pavani
P
Mocharla
Ulf
U
Landmesser
Sarah R
SR
Haile
Roberto
R
Corti
Paul M
PM
Vanhoutte
Thomas F
TF
Lüscher
Georg
G
Noll
Frank
F
Ruschitzka
D000082:Acetaminophen / Q000009:adverse effects* / Q000494:pharmacology*; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D003324:Coronary Artery Disease / Q000503:physiopathology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology; D011446:Prospective Studies; D012307:Risk Factors; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000082:Acetaminophen