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2 Minute Medicine Rewind November 14, 2016
Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis
Celecoxib is a selective COX-2 inhibitor used for analgesia as an alternative to nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), however the cardiovascular risk profile is controversial. In this multicenter, industry sponsored, randomized control trial, 24,081 patients with osteoarthritis or rheumatoid arthritis were randomized to daily celecoxib, naproxen, or ibuprofen and followed for a primary endpoint of cardiovascular death, myocardial infarction, or nonfatal stroke. This was a non-inferiority trial with a prespecified boundary of an HR of 1.12 or less. In the trial, 2.3% of patients in the celecoxib arm experienced the primary endpoint, compared to 2.5% of patients in the naproxen arm (HR for celecoxib 0.93, p < 0.001 for inferiority), and 2.7% in the ibuprofen arm (HR for celecoxib 0.85, p < 0.001 for inferiority). 68.8% of patients discontinued the study drug, however similar results were found in on-treatment analysis. For patients taking celecoxib, there was statistically significantly less gastrointestinal bleeding and renal dysfunction. The authors conclude celecoxib is noninferior to ibuprofen or naproxen in relation to cardiovascular health.
There continues to exist significant variation in the intensity of statin therapy in patients with atherosclerotic cardiovascular disease, however there is limited data on the differences in clinical outcomes based on the intensity of statin therapy. In this retrospective cohort study of 509,766 patients with atherosclerotic heart disease in the US Veterans Affairs health care system, investigators compared 1 year mortality with the intensity of statin therapy. The investigators found a dose-dependent effect on 1 year mortality with 4.0% mortality in patients receiving high-intensity statin, 4.8% mortality in patients receiving moderate-intensity statin, 5.7% mortality in patients receiving low-intensity statin, and 6.6% mortality in patients receiving no statin. Additionally, patients receiving maximum doses of a high intensity statin had lower mortality (HR 0.9, 95% CI 0.87 to 0.94) compared to patients receiving submaximal doses of a high intensity statin. In this cohort of patients in the VA healthcare system, the intensity of statin therapy was associated with survival benefit.
Ticagrelor versus Clopidogrel in Symptomatic Peripheral Artery Disease
Peripheral artery disease from atherosclerosis is medically managed with antiplatelet pharmacotherapy such as aspirin and clopidogrel. Ticagrelor is a more potent P2Y12 antiplatelet agent than clopidogrel and is tried to assess its clinical efficacy. In this randomized, multicenter, industry sponsored trial, 13,885 patients with symptomatic peripheral artery disease were randomized to either ticagrelor or clopidogrel and followed for a median of 30 months for a primary endpoint of cardiovascular death, myocardial infarction, or ischemic stroke. The study found a nonstatistically significant difference between ticagrelor and clopidogrel (10.8% vs. 10.6%, HR 1.02, p = 0.65). There was also similar rates of limb ischemia (1.7%) and major bleeding (1.6%) in each group. This study did not show clinical benefit in the use of ticagrelor over clopidogrel.
Anakinra is an interleukin 1b recombinant receptor antagonist and is thought to be potentially beneficial in colchicine-resistant and corticosteroid-dependent recurrent pericarditis. In this, multicenter, placebo controlled, randomized trial of 21 Italian patients with recurrent pericarditis, patients were randomized to anakinra or placebo and followed for recurrent pericarditis. After a median follow-up of 14 months, there was a statistically significant decrease in the number of recurrences (90% vs. 18.2%, p < 0.001). For patients on anakinra, there were local skin reactions, herpes zoster, transaminitis, and ischemic optic neuritis. Although this was a small trial of a rare condition, further studies of anakinra should be undertaken to confirm its efficacy in recurrent pericarditis.
Image: PD
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