Day and Graham (1) have provided an extremely useful summary of the balancing of risks and benefits required when prescribing cyclo-oxygenase inhibitors. However in concentrating on the apparent cardiovascular safety of high-dose naproxen, it is disappointing that they did not explore the potential benefits of flurbiprofen when considering cardiovascular risk.
The non-steroidal anti-inflammatory agent flurbiprofen is widely available at low cost as a generic and anti-platelet effects were reported as long ago as the early 1970s (2). More recent studies have shown that, similar to naproxen, therapeutic levels of flurbiprofen significantly inhibit platelet aggregation and importantly at least in in vitro studies, do not affect the anti-platelet effects of aspirin (3).
As Day and Graham point out naproxen is generally regarded as the NSAID with the lowest cardiovascular risk, typically having a neutral effect: in contrast to the increased risk associated with high-dose coxibs or ibuprofen or diclofenac (4). However the anti-platelet effect of flurbiprofen has actually been shown to be associated with a significant reduction in adverse cardiovascular events. In randomized double-blind trial of therapy following successful thrombolysis or angioplasty for acute myocardial infarction, flurbiprofen (50 mg twice daily) was significantly better than placebo: after 6 months reinfarction was reduced by 71.5% and revascularisation by 50% (5). As would be expected, gastrointestinal bleeding was increased 3-fold, comparable to rates with other NSAIDs (1,4). Flurbiprofen is licenced for use as an anti-platelet agent in France and advocated in guidelines to reduce thrombotic episodes (6).
Although less commonly used clinically and not used at all as a comparator in any of the recent large coxib trials, flurbiprofen seems to have clinically effective protective effects against cardiovascular events. Further larger scale studies would further inform our decision-making but it would be wise to consider flurbiprofen as an option when increased cardiovascular risk is a concern.
1. Day R and Graham G Non-steroidal anti-inflammatory drugs (NSAIDs). BMJ (2013) 346: 3195
2. Davies T, Lederer DA, McNichol S, McNichol GP. The effect of flurbiprofen (2-(2-flouro-4-biphenylyl)proprionic acid) on platelet function and blood coagulation. Throm Res (1974) 5: 667-83
3. Yokoyama H, Ito N, Soeda S, Ozaki M, Watanabe M, Kashiwakura E, Kawada T, Ikeda N, Tokuoka K, Kitagawa Y, Yamada Y. Influence of non-steroidal anti-inflammatory drugs on antiplatelet effect of aspirin.. J Clin Pharm Ther (2013) 38: 12-5
4. Coxib and traditional NSAID Trialists (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet (2013) doi: 10.1016/S0140-6736(13)60900-9. [Epub ahead of print]
5. Broucher ML. Evaluation of flurbiprofen for prevention of reinfarction and reocclusion after successful thrombolysis or angioplasty in acute myocardial infaction. Eur Heart J (1993) 14: 951-7
6. Nalpoleon B, Boneu B, Maillard L, Samama C-M, Schved J-F, Gay G, Ponchon T, Sautereau D, Canard J-M. Guidelines of the French Society for Digestive Endoscopy (SFED). Management of Patients on anticoagulants or antiplatelet agents before digestive endoscoopy. Endoscopy (2006) 38: 632-638
Rapid Response:
Re: Non-steroidal anti-inflammatory drugs (NSAIDs)
Day and Graham (1) have provided an extremely useful summary of the balancing of risks and benefits required when prescribing cyclo-oxygenase inhibitors. However in concentrating on the apparent cardiovascular safety of high-dose naproxen, it is disappointing that they did not explore the potential benefits of flurbiprofen when considering cardiovascular risk.
The non-steroidal anti-inflammatory agent flurbiprofen is widely available at low cost as a generic and anti-platelet effects were reported as long ago as the early 1970s (2). More recent studies have shown that, similar to naproxen, therapeutic levels of flurbiprofen significantly inhibit platelet aggregation and importantly at least in in vitro studies, do not affect the anti-platelet effects of aspirin (3).
As Day and Graham point out naproxen is generally regarded as the NSAID with the lowest cardiovascular risk, typically having a neutral effect: in contrast to the increased risk associated with high-dose coxibs or ibuprofen or diclofenac (4). However the anti-platelet effect of flurbiprofen has actually been shown to be associated with a significant reduction in adverse cardiovascular events. In randomized double-blind trial of therapy following successful thrombolysis or angioplasty for acute myocardial infarction, flurbiprofen (50 mg twice daily) was significantly better than placebo: after 6 months reinfarction was reduced by 71.5% and revascularisation by 50% (5). As would be expected, gastrointestinal bleeding was increased 3-fold, comparable to rates with other NSAIDs (1,4). Flurbiprofen is licenced for use as an anti-platelet agent in France and advocated in guidelines to reduce thrombotic episodes (6).
Although less commonly used clinically and not used at all as a comparator in any of the recent large coxib trials, flurbiprofen seems to have clinically effective protective effects against cardiovascular events. Further larger scale studies would further inform our decision-making but it would be wise to consider flurbiprofen as an option when increased cardiovascular risk is a concern.
1. Day R and Graham G Non-steroidal anti-inflammatory drugs (NSAIDs). BMJ (2013) 346: 3195
2. Davies T, Lederer DA, McNichol S, McNichol GP. The effect of flurbiprofen (2-(2-flouro-4-biphenylyl)proprionic acid) on platelet function and blood coagulation. Throm Res (1974) 5: 667-83
3. Yokoyama H, Ito N, Soeda S, Ozaki M, Watanabe M, Kashiwakura E, Kawada T, Ikeda N, Tokuoka K, Kitagawa Y, Yamada Y. Influence of non-steroidal anti-inflammatory drugs on antiplatelet effect of aspirin.. J Clin Pharm Ther (2013) 38: 12-5
4. Coxib and traditional NSAID Trialists (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet (2013) doi: 10.1016/S0140-6736(13)60900-9. [Epub ahead of print]
5. Broucher ML. Evaluation of flurbiprofen for prevention of reinfarction and reocclusion after successful thrombolysis or angioplasty in acute myocardial infaction. Eur Heart J (1993) 14: 951-7
6. Nalpoleon B, Boneu B, Maillard L, Samama C-M, Schved J-F, Gay G, Ponchon T, Sautereau D, Canard J-M. Guidelines of the French Society for Digestive Endoscopy (SFED). Management of Patients on anticoagulants or antiplatelet agents before digestive endoscoopy. Endoscopy (2006) 38: 632-638
Competing interests: No competing interests