Science News from ESC 2017

European Society of Cardiology's ESC Congress
August 26 – 30, 2017 | Barcelona, Spain

Chronic NSAID Use and Ambulatory Blood Pressure:  PRECISION-ABPM in Perspective

Elliott Antman, MD

The Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen (PRECISION) trial, presented at the AHA 2016 Scientific Sessions (see Science News coverage) conference and published in the New England Journal of Medicine is challenging to interpret, according to Elliott Antman, MD, senior physician at Brigham and Women's Hospital, associate dean for Clinical and Translational Research at Harvard Medical School, and a past president of the American Heart Association.

With the exception of aspirin, almost all nonsteroidal anti-inflammatory drugs (NSAIDs), including those available over-the-counter, have adverse consequences on the cardiovascular system. PRECISION’s purpose was to compare the cardiovascular safety for the chronic use of three NSAIDS used to treat arthritis. Unfortunately, significant limitations of the PRECISION trial limit our ability to interpret the relative pharmacological effects of ibuprofen or naproxen compared with celecoxib.

Specifically:
  • Asymmetric dosing confounded the trial. "When you’re comparing treatments, one of the first questions you have to ask is whether they are pharmacologically comparable," Dr. Antman said. "We believe that the doses of the drugs used in the various treatment arms were not comparable. The dose of celecoxib was relatively low compared to the doses of ibuprofen and naproxen."
     
  • Poor adherence to the protocol and low retention in the study negatively impacted the trial. A large number of the original 24,000 subjects dropped out over the course of the 10 years of the trial, and could not be reached for follow up---making it impossible to evaluate their outcomes.

Dr. Antman detailed the impact of these issues in his May 2017 Circulation article, Evaluating the Cardiovascular Safety of Nonsteroidal Anti-Inflammatory Drugs. The same concerns apply to a PRECISION trial sub-study analysis reported at European Society of Cardiologists (ESC) Conference in Barcelona, Spain and must be considered in any review of those findings. In fact, Dr. Antman said, the same problems with the PRECISION trial apply to the sub-study analysis and become amplified because it considers only a few hundred patients.

"The blood pressure seemed to be higher in individuals who received ibuprofen (in relatively high doses) compared to celecoxib (in relatively low dose),” Dr. Antman notes. “That is not surprising since the effect of NSAIDs is to cause the kidneys to retain sodium and water. The higher the dose of the NSAID received, the greater the chance of volume expansion and elevation of blood pressure."

Clinicians are reminded that the 2007 Scientific Statement from the American Heart Association remains an authoritative, helpful resource for providers seeking guidance on NSAIDS, Dr. Antman said. Dr. Antman emphasized, "It seems most reasonable to focus the use of NSAIDs on patients at lowest cardiovascular risk, using a drug with the lowest risk of producing cardiovascular events, in the lowest dose needed to control symptoms, and for the shortest period of time required."