Celecoxib and Etoricoxib may reduce risk of ischemic stroke in patients with rheumatoid arthritis: A nationwide retrospective cohort study

Abstract

Background and purposePrevious studies reported conflicting results about the risk of ischemic stroke associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA). We aimed to investigate two specific COX-2 inhibitors, Celecoxib and Etoricoxib, and their corresponding effects on the risk of ischemic stroke in patients with RA.Patients and methods10,857 patients newly diagnosed with RA were identified and sampled from the Taiwanese National Health Insurance Research Database during the period from 2001 to 2009. The identification of RA was based on the criteria of ICD-9-CM diagnosis code 714.0. Patients diagnosed with cerebrovascular disease and those receiving RA treatment prior to the first diagnosis of RA were excluded. Study endpoint was ischemic stroke, defined by ICD-9-CM code. Cox proportional hazard models and Kaplan Meier curves were used to reveal covariates and differences by drugs in the risk of ischemic stroke. Dosages for Celecoxib were defined as ≤ 200 and >200 mg/day; those for Etoricoxib were 0 and >0 mg/day.ResultsAmong 7,904 RA patients, 6,669 did not take Celecoxib and 564 (8.46%) of them experienced an ischemic stroke event. Of the 597 individuals who took ≤ 200 mg/day of Celecoxib, 58 (9.72%) had strokes. Of the 638 patients who took >200 mg/day of Celecoxib, 38 (5.96%) eventually experienced a stroke. Among the 7,681 patients who did not take Etoricoxib, 654 (8.51%) experienced an ischemic stroke, while 6 (2.69%) in 223 patients who consumed Etoricoxib had a stroke event. Consuming more than 200 mg of Celecoxib per day for <3.5 years lowered the incidence rate for strokes [hazard ratio (HR) 0.67, 95% Confidence Interval (CI) 0.48–0.93 for dosage and HR 0.22, 95% CI 0.10–0.46 for duration, both p < 0.001], while consuming any dosage of Etoricoxib significantly decreases the possibility (HR 0.35, 95% CI 0.16–0.80, p < 0.001). On the other hand, consuming Etoricoxib for 8 years might have a neutral or even a potentially protective effect compared to at 3.8 years.ConclusionThis population-based retrospective cohort study has shown that Celecoxib and Etoricoxib reduce the risk of ischemic stroke in patients with RA in a dose- and time-dependent manner.

Identification of hypoxia- and immune-related biomarkers in patients with ischemic stroke

“…Furthermore, a double-blind controlled study suggested that Nimodipine might offer therapeutic benefits in the management of acute stroke [ 75 ]. A population-based retrospective cohort study has shown that celecoxib reduce the risk of ischemic stroke in patients with rheumatoid arthritis in a dose- and time-dependent manner [ 76 ]. Relevant research also suggests that substances such as cyclosporine [ 77 ], vitamin E [ 78 ], deferoxamine [ 79 ], curcumin [ 80 ], and daidzein [ 81 ] may offer certain advantages in the prevention of ischemic stroke.…”

Comparison of cardiorenal safety of nonsteroidal anti-inflammatory drugs in the treatment of arthritis: a network meta-analysis

“…This may be because of their specific effects on COX-2, which is not highly related to the time of drug exposure and the extent of relative selectivity. Among coxibs, celecoxib is associated with a relatively lower risk of cardiovascular events, which may be due to its low specificity for COX-2 ( 38 , 48 ). Johnsen et al ’s 2005 study ( 49 ) also supported this idea, but conflicted in another regard.…”

Stroke risk in rheumatoid arthritis patients: exploring connections and implications for patient care

“…Long-term use of Celecoxib may gradually lead to adverse effects such as increased blood pressure and a potentially prothrombotic environment, which can elevate the relative risk of ischemic stroke [ 152 ]. A population-based retrospective cohort study suggests that Celecoxib and Etoricoxib may be associated with a reduced risk of first-occurrence ischemic stroke in RA patients, with the risk reduction dependent on the dose and duration of use [ 153 ]. These paradoxical results of Celecoxib being protective at a higher dose in a shorter duration but harmful in a longer duration, as well as the neutral to slight protective effects of Etoricoxib, require further investigation to understand their underlying physiological mechanisms.…”