Risk of ischemic stroke associated with non‐steroidal anti‐inflammatory drugs and paracetamol: a population‐based case‐control study

Abstract

To cite this article: Garc ıa-Poza P, de Abajo FJ, Gil MJ, Chac on A, Bryant V, Garc ıa-Rodr ıguez LA. Risk of ischemic stroke associated with non-steroidal anti-inflammatory drugs and paracetamol: a population-based case-control study. J Thromb Haemost 2015; 13: 708-18.Summary. Objective: To assess the risk of non-fatal ischemic stroke associated with non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol. The effects of dose, duration of treatment, background cardiovascular (CV) risk and use of concomitant aspirin were studied. Methods: We performed a population-based case-control study. Patients were considered exposed if they were on treatment within a 30-day window before the index date. We estimated adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) using logistic regression. Results: Two thousand eight hundred and eighty-eight cases and 20 000 controls were included. No increased risk was observed with traditional NSAIDs as a group (OR = 1.03; 95% CI, 0.90-1.19), but results varied across individual agents and conditions of use. An increased risk was found with diclofenac (OR = 1.53; 95% CI, 1.19-1.97), in particular when used at high doses (OR = 1.62; 1.06-2.46), over long-term periods (> 365 days; OR = 2.39; 1.52-3.76) and in patients with a high background CV risk (OR = 1.78; 1.23-2.58), as well as with aceclofenac when used at high doses (OR = 1.67; 1.05-2.67), in long-term treatments (OR = 2.00; 1.14-3.53) and in patients with CV risk factors (OR = 2.33; 1.40-3.87). No association was found with ibuprofen (OR = 0.94; 0.76-1.17) or naproxen (OR = 0.68; 0.36-1.29). The concomitant use of aspirin did not show a significant effect modification. Paracetamol did not increase the risk overall (OR = 0.97; 0.85-1.10) or in patients at high CV risk (OR = 0.94; 0.78-1.14). Conclusions: Diclofenac and aceclofenac increase the risk of ischemic stroke while ibuprofen and naproxen do not. Dose, duration and baseline CV risk, but not aspirin use, appear to modulate the risk. Paracetamol does not increase the risk, even in patients with a high background CV risk.

Non-steroidal anti-inflammatory drugs and risk of cerebrovascular events in patients with osteoarthritis: a nested case–control study

“…Nevertheless, few investigations have focused on cerebrovascular events [9][10][11]29]. Four studies included in a meta-analysis report an increased risk of ischemic stroke for diclofenac and rofecoxib, while an absence of risk is found for ibuprofen and naproxen [11].…”

“…However, most of the previous studies were focused on ischemic cardiomyopathy or composite outcomes of ischemic cardiomyopathy, stroke or heart failure [6][7][8]. On the other hand, the evidence is scarce for an association between NSAIDs, especially for individual molecules, and the risk of ischemic stroke/transient ischemic attack (TIA) or hemorrhagic stroke [9][10][11]. Indeed, prior research concerned the three most widely used NSAIDs worldwide, namely diclofenac, ibuprofen and naproxen, while the most commonly prescribed NSAIDs in Italy are diclofenac, nimesulide and ketoprofen [12].…”

Seguridad de los AINE y de los opioides

“… Antecedentes de patología cardiovascular: los AINE aumentan el riesgo de muerte y estancia hospitalaria por IAM e insuficiencia cardiaca de 3 a 5 veces (36). En postinfartados y factores de riesgo cardiovascular este riesgo se incrementa y contraindica el uso de COXIB (37)(38)(39)(40).…”

Paracetamol, Ibuprofen, and Recurrent Major Cardiovascular and Major Bleeding Events in 19 120 Patients With Recent Ischemic Stroke

“…Paracetamol intake was not associated with an increase in stroke rate in a recent population-based case-control study, nor to myocardial infarction in other studies. [12][13][14] In an acute stroke setting, paracetamol treatment to control mildto-moderate hyperthermia (37-39°C) seemed to be associated with a better final outcome, reducing disability at 3 months according to the modified Rankin scale. 15 Although there is a more commonly accepted belief that other NSAIDs, such as ibuprofen, have a higher vascular risk, there are still conflicting data in the literature.…”

“…Although some authors claim that ibuprofen intake is associated with an increase in vascular risk, 16 others have found no such association. 12,13 NSAIDs-associated bleeding risk is well known, particularly of a gastrointestinal origin. 16 Their use represents an independent risk factor in patients with an antithrombotic treatment, even when prescribed for a short term.…”