Reducing Cardiovascular Risks of Nonsteroidal Anti-Inflammatory Drugs by Using Topical Formulations

Abstract

Farkouh and Greenberg 1 Farkouh M.E. Greenberg B.P. An evidence-based review of the cardiovascular risks of nonsteroidal anti-inflammatory drugs. Am J Cardiol. 2009; 103: 1227-1237 Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar presented a timely and valuable review of the cardiovascular risk profiles of nonsteroidal anti-inflammatory drugs (NSAIDs). This review is of clinical importance because of the widespread availability and monitored and unmonitored use of NSAIDs, coupled with their potential to affect multiple organs, including the cardiovascular system. However, a discussion of topical NSAIDs is absent from this review. International guidelines recommend considering topical NSAIDs as a first-line therapy for osteoarthritis of the knees 2 Zhang W. Moskowitz R.W. Nuki G. Abramson S. Altman R.D. Arden N. Bierma-Zeinstra S. Brandt K.D. Croft P. Doherty M. Dougados M. Hochberg M. Hunter D.J. Kwoh K. Lohmander L.S. Tugwell P. OARSI recommendations for the management of hip and knee osteoarthritis, part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage. 2008; 16: 137-162 Abstract Full Text Full Text PDF PubMed Scopus (2012) Google Scholar and hands. 3 Zhang W. Doherty M. Leeb B.F. Alekseeva L. Arden N.K. Bijlsma J.W. Dinçer F. Dziedzic K. Häuselmann H.J. Herrero-Beaumont G. Kaklamanis P. Lohmander S. Maheu E. Martín-Mola E. Pavelka K. Punzi L. Reiter S. Sautner J. Smolen J. Verbruggen G. Zimmermann-Górska I. EULAR evidence based recommendations for the management of hand osteoarthritis: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2007; 66: 377-388 Crossref PubMed Scopus (498) Google Scholar Topical NSAIDs are often used with the therapeutic rationale of minimizing systemic NSAID exposure, with a focus on those who have risk factors but require the therapeutic benefit of an anti-inflammatory agent. Pharmacokinetic data show that using topical diclofenac 1% gel results in a 150-fold lower peak plasma concentration and 17-fold lower mean plasma concentration of diclofenac relative to a comparable dose of oral diclofenac. 4 Kienzler J, Gold M, Nollevaux F. Systemic bioavailability of topical diclofenac sodium gel 1% versus oral diclofenac sodium in healthy volunteers. J Clin Pharmacol New Drugs. In press. Google Scholar Discussion of the cardiovascular risk implications of using topical agents to reduce systemic NSAID exposure would have been an interesting addition to this elaborate review and clinically relevant jointly to patients and clinicians who are using or considering the option of using topical NSAIDs. In my clinical practice, we have observed a paucity of systemic adverse events with topical diclofenac 1% gel. This formulation provides an additional opportunity for consideration for those patients with creatinine clearance <50 ml/min, because these patients have renal prostaglandin processes that are blunted by selective and nonselective NSAIDs. With these patients, we have observed no changes in renal function or renal events precipitated by the daily use of topical diclofenac 1% gel. There have also been no reports of elevations in international normalized ratio among my practice's patients taking warfarin or elevations of blood pressure in those with hypertension when using the product, nor have we observed any association with thrombotic events. An Evidence-Based Review of the Cardiovascular Risks of Nonsteroidal Anti-Inflammatory DrugsAmerican Journal of CardiologyVol. 103Issue 9PreviewNonsteroidal anti-inflammatory drugs (NSAIDs), both nonselective and cyclooxygenase-2–specific inhibitors, are commonly used medications for the relief of acute and chronic pain associated with a wide range of medical conditions. Because of the extensive use of these agents, adverse events that occur infrequently may still affect the overall risk/benefit ratio of this class of medications. Serious adverse cardiovascular (CV) events have been reported with NSAID use, but unfortunately, definitive evidence regarding the precise CV risk associated with these drugs, as a class and individually, is lacking. Full-Text PDF