Non-steroidal anti-inflammatory drugs and risk of cerebrovascular events in patients with osteoarthritis: a nested case-control study.
Recent studies show that the risk of cardiovascular adverse events for certain traditional non-steroidal anti-inflammatory drugs (NSAIDs) is similar to that of rofecoxib. While these results are focused on ischemic cardiomyopathy, there is little evidence concerning the risk of ischemic stroke/transient ischemic attack and hemorrhagic stroke. Additionally, there is no information on nimesulide and ketoprofen, the most frequently prescribed NSAIDs in Italy, along with diclofenac. This study aims to determine whether the use of NSAIDs is associated with an increased risk of cerebrovascular events in Italy. We performed a case-control analysis nested in a cohort of patients with osteoarthritis between 2002 and 2011 who were newly treated with NSAIDs. The patients were followed until December 31, 2012. Conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI) of cerebrovascular events (index date) associated with current (until 30 days before the index date), recent (31-365 days) and past (>365 days) use of NSAIDs. Within a cohort of 29,722 patients, 1566 cases (1546 matched with controls) were identified (incidence rate = 11.0/1000 person-years). The overall rate of cerebrovascular event was not elevated with current NSAIDs overall when compared with past use. Among individual NSAIDs, diclofenac and ketoprofen were the molecules significantly associated with an increased rate of cerebrovascular events (OR = 1.53; 95% CI 1.04-2.24; OR = 1.62; 95% CI 1.02-2.58, respectively). The most frequent event was hemorrhagic stroke following the use of ketoprofen (OR = 2.09; 95% CI 1.05-4.15). Diclofenac and ketoprofen seemed to increase the risk of cerebrovascular events. These findings might influence the choice of NSAIDs according to patient characteristics.
Health Search, Italian College of General Practitioners and Primary Care, Via Sestese 61, 50141, Florence, Italy. lapi.francesco@simg.it.
Francesco
F
Lapi
Pharmacology Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
Carlo
C
Piccinni
Health Search, Italian College of General Practitioners and Primary Care, Via Sestese 61, 50141, Florence, Italy.
Monica
M
Simonetti
Health Search, Italian College of General Practitioners and Primary Care, Via Sestese 61, 50141, Florence, Italy.|Department of Health Sciences, University of Florence, Florence, Italy.
Miriam
M
Levi
Italian College of General Practitioners and Primary Care, Florence, Italy.
Pierangelo
P
Lora Aprile
Health Search, Italian College of General Practitioners and Primary Care, Via Sestese 61, 50141, Florence, Italy.
Iacopo
I
Cricelli
Italian College of General Practitioners and Primary Care, Florence, Italy.
Claudio
C
Cricelli
Intensive Care Unit, Department of Anesthesia and Postoperative, Istituto Ortopedico Rizzoli, Bologna, Italy.
Andrea
A
Fanelli
D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D016022:Case-Control Studies; D002561:Cerebrovascular Disorders / Q000453:epidemiology*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000150:complications / Q000188:drug therapy*
D000894:Anti-Inflammatory Agents, Non-Steroidal
Cerebrovascular events; Drug safety; Non-steroidal anti-inflammatory drugs; Osteoarthritis