Researchers found that using NSAIDs for one week or more increases a person’s risk of experiencing an AMI. The NSAIDs in the study include celecoxib, diclofenac, ibuprofen, naproxen and rofecoxib. Low-dose aspirin was not included.
Each NSAID-use category compared the date of AMI for cases and matched the date for controls with NSAID non-use in the prior year, also looking at the posterior probability of AMI. The cohort included 446,763 individuals, of whom 61,460 had an AMI. The corresponding odds ratios were 1.24 for celecoxib, up to 1.53 for naproxen and 1.58 for rofecoxib, which is no longer available in the U.S.
A greater AMI risk was associated with higher NSAID doses and within the first month (Days 8–30) of continued use. Drugs and doses associated with this risk were >200 mg celecoxib, >100 mg diclofenac, >1,200 mg ibuprofen and >750 mg naproxen. The AMI risk with celecoxib did not seem greater than with traditional NSAIDs. Additionally, the AMI risk for using NSAIDs for more than one month did not exceed the risk associated with shorter durations of use.
In the study, the authors note that the absolute risk is very small and varies based on a patient’s baseline risk. They also note that as patients use these agents for longer treatment durations, the risk does not seem to continue to increase. However, they caution that they only studied patients with one AMI, not repeat AMIs. To be prudent, they note, patients should use NSAIDs for as short a time as possible.
Increased Risk of Leg & Foot Amputations with Canagliflozin
On May 16, the FDA confirmed that canagliflozin-treated patients underwent leg and foot amputations about twice as often as placebo-treated patients. This announcement was based on the results of two clinical trials: the Canagliflozin Cardiovascular Assessment Study (CANVAS) and A Study of the Effects of Canagliflozin on Renal Endpoints in Adult Participants with Type 2 Diabetes Mellitus (CANVAS-R). Canagliflozin (Invokana, Invokamet, Invokamet XR) is an oral sodium-glucose cotransporter-2 (SGLT2) inhibitor used to treat Type 2 diabetes.6
The FDA is requiring new warnings, including a boxed warning, be added to the canagliflozin drug labels to describe this risk.
Patients taking canagliflozin are being asked to notify their healthcare professionals if they develop any new pain, tenderness, sores, ulcers or infections in their feet or legs. Healthcare professionals should consider factors that may predispose patients to the need for amputations, such as a history of prior amputation, peripheral vascular disease, neuropathy and/or diabetic foot ulcers, before starting a patient on canagliflozin. Patients taking canagliflozin should be monitored for signs and symptoms indicative of these predisposing conditions, and canagliflozin should be discontinued if they arise.
