Clinical Pharmacology and Cardiovascular Safety of Naproxen

Abstract

[...]regulatory authorities should revisit label information periodically to ensure labeling reflects the current understanding of benefits and risks. 1Introduction 1.1 Non-Steroidal Anti-Inflammatory Drug (NSAID) Background 1.1.1 Therapeutic Importance Musculoskeletal aches and pains are one of the most common medical complaints around the world, and increasing life expectancies are driving an increased incidence of degenerative joint disease, burdening patients and healthcare systems [1]. The US FDA Advisory Committee meetings in both 2005 and 2014 concluded that NSAIDs increased the risk of myocardial infarction (MI) in high-risk individuals, and they supported the need for additional label warnings and studies to further clarify whether the increased risk was truly a class effect or the result of cyclooxygenase (COX)-2 selectivity. The 2014 FDA Advisory Committee meeting on the cardiovascular risk of NSAIDs included an FDA review of data available after 2005, highlighting a potential lower cardiovascular risk with naproxen than with other NSAIDs, as well as a discussion of the progress of PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen Or Naproxen), an ongoing cardiovascular safety study [9]. The role of COX-1 is to maintain a basal rate of prostanoid biosynthesis [13], including the constitutive synthesis of prostaglandin (PG)-E2 by the gastrointestinal tract to mediate gastro-protection from stomach acid and maintain gastrointestinal homeostasis, and generation of thromboxane A2 (TXA2) by activated platelets in response to injury [12, 15]. Palmer R, Weiss R, Zusman RM, Haig A, Flavin S, McDonald B. Effects of nabumetone, celecoxib, and ibuprofen on blood pressure control in hypertensive...