Advil, Alleve, and Tylenol Do Not Increase Stroke Risk, But Diclofenac Does

It's been shown that NSAIDS, including, notoriously, some newer, and heavily marketed ones such as the cox-2 inhibitors celecoxib (Celebrex) and the withdrawn-from-market rofecoxib (Vioxx), slightly increase the risk of MI. Because of that risk, and the general association of stroke with MI risks, it has been suspected that NSAIDs might also, as a general class, increase stroke risk.

This appears not to be the case. In the study below, the more popular NSAIDs in the US, naproxen and ibuprofen, do not seem to increase stroke risk. Diclofenac (Voltaren) does, however. Aspirin was neutral in this study, though it has been shown to to lower brain infarctions and increase bleeds in other studies.

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ABSTRACT

Risk of ischaemic stroke associated with non-steroidal antiinflammatory drugs and paracetamol: a population-based case-control study

Journal of Thrombosis and Haemostasis, 01/27/2015

GarcíaPoza P, et al.

The authors aim to assess the risk of nonfatal ischaemic stroke associated with NSAIDs and paracetamol. The effects of dose, duration of treatment, background cardiovascular (CV) risk and use of concomitant aspirin were studied. Diclofenac and aceclofenac increase the risk of ischaemic 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 at high background CV risk.

Methods

The authors 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. They estimated adjusted odds ratios (ORs) and their 95% CI using logistic regression.

Results

2888 cases and 20000 controls were included. No increased risk was observed with traditional NSAIDs as a group (OR= 1.03; 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 at 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), 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).