The use of certain nonsteroidal anti-inflammatory drugs (NSAIDs) by healthy people is associated with an increased risk of cardiovascular death, but naproxen (Aleve, Bayer Consumer) appears to have a safer cardiovascular risk profile, according to a study published online June 8 in Circulation: Cardiovascular Quality and Outcomes, as reported by HealthDay News.
The risk of gastrointestinal (GI) complications because of the use of nonsteroidal anti-inflammatory drugs (NSAIDs) varies by the specific drug and dosage, and those with a slow-release formulation or long half-life are associated with a greater risk, according to research published in the June issue of Arthritis & Rheumatism, as reported by HealthDay News.
Researchers conducted a systematic review of observational studies from 2000 to 2008 on NSAIDs and upper GI bleeding or perforation. The article criteria was to report case-control or cohort studies evaluating traditional NSAID or coxib use and upper GI bleeding/perforation in the general population, and provide either an estimate, or enough data to estimate, a relative risk comparing NSAID users with nonusers. The pooled relative risk estimates of upper GI bleeding/perforation for individual NSAIDs was calculated, as well as whether the degree of inhibition of whole blood cyclooxygenase-1 (COX-1) and COX-2 in vitro by average circulating concentrations predicted the relative risk of upper GI bleeding/perforation.
The relative risk of upper GI bleeding/perforation was 4.50 for traditional NSAIDs and 1.88 for coxibs. Relative risks varied widely by specific drug: 1.42 for celecoxib (Celebrex, Pfizer); 1.44 for aceclofenac (Hifenac, Intas Pharma), which is not available in the United States; 2.12 for rofecoxib, which was pulled off the market in the United States and worldwide in 2004 because of heart-related side effects, but the study period included calendar years prior to the withdrawal; 2.69 for ibuprofen (Advil, Wyeth Consumer Healthcare and Motrin, McNeil Consumer Healthcare); 3.98 for diclofenac (Voltaren, Novartis Pharmaceuticals); 4.15 for meloxicam (Mobic, Boehringer Ingelheim); 5.40 for indomethacin (Indocin, Merck & Co.); 5.57 for ketoprofen (Oruvail, Wyeth); 5.63 for naproxen (Aleve, Bayer Consumer); 9.94 for piroxicam (Feldene, Pfizer); and 14.54 for ketorolac (Toradol, Roche Pharmaceuticals).
NSAIDs with a longer plasma half-life or extended-release formulations and those that inhibited both COX-1 and COX-2 were associated with a higher risk of upper GI bleeding/perforation.
“All NSAIDs share an increased risk of serious complications in the upper GI tract such as bleeding,” Luis Alberto García Rodríguez, MD, research leader and director of CEIFE – the Spanish Centre for Pharmacoepidemiologic Research in Madrid, told Formulary. “Yet, some present a greater risk than others as used in daily practice. We were able to show that one of the predictors of increased risk is a marked inhibition of two isozymes (COX-1 and COX-2) in the GI tract. Also, NSAIDs with long half-lives, or delivered as slow-release formulations, as well as NSAIDs taken at high dose will result in greater risk of developing these complications.”
NSAIDs with short half-life and used at low daily dose, such as ibuprofen, have a smaller risk of upper GI bleeding, Dr. Rodríguez said. NSAIDs with long half-life and potent inhibition of both cyclooxigenase, such as piroxicam, carry the greatest risk. NSAIDs interfering little with the inhibition of COX-1 carry a smaller risk such as celecoxib.
“Beyond the risk intrinsic to NSAIDs, old age and a history of peptic ulcer are two other major factors increasing the risk of upper GI bleeding,” he said.
One of the study’s authors disclosed financial relationships with the pharmaceutical industry.
FDA Approves Two More Denosumab Biosimilars, Conexxence and Bomyntra
March 27th 2025The fourth pair of denosumab biosimilars, Conexxence and Bomyntra, are expected to launch in the United States in mid 2025, as a result of a global settlement with Amgen, according to a company news release.
Read More
FDA Approves First Drug for Excess Hunger in Prader-Willi Syndrome
March 27th 2025Vykat XR will be available in April to treat the intense hunger that is a hallmark of the rare genetic disease Prader-Willi syndrome. The price is based on a patient’s weight, and the average patient in the clinical trials would have had an average annual cost of $466,200 for the first year.
Read More
FDA Approves Amvuttra for ATTR-CM in Extended Label
March 21st 2025This expanded indication for Amvuttra makes it the first and only FDA-approved treatment for transthyretin amyloidosis with cardiomyopathy (ATTR-CM) and the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults.
Read More