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Thursday, 25 August 2016 00:00

NSAIDs and cardiovascular events – frequently asked questions

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Does paracetamol increase the risk of CVD events?

Paracetamol has a different mode of action to NSAIDs and is unlikely to influence heart function by the same mechanisms as NSAIDs. Therefore, paracetamol may be considered first choice for patients with, or at risk of, cardiovascular disease.


Why does paracetamol not act like the NSAIDs?

While COX-2 inhibitors and non-selective NSAIDs inhibit prostaglandin synthesis in many tissues of the body, paracetamol acts predominantly on the production of prostaglandins in the central nervous system.5 Therefore, there is little potential for paracetamol to affect the kidney, blood vessel and heart systems that are detrimentally affected by NSAIDs.


Why is this issue important now?

The latest paper showing up to a 63% increase in the risk of serious CVD events with NSAIDs, authored by Kearney et al, has been released by a highly eminent group with vast experience in the analysis of data relating to analgesics.10 The study showed that high doses of non-selective NSAIDS, such as ibuprofen, were associated with a similar increase in the risk of vascular events to COX-2 inhibitors. This meta-analysis included data from 138 trials among 145,373 patients, providing a much more reliable estimate of the cardiovascular risk of these drugs, as individual trials were too small to study this question.

The production of this paper by such a well recognised group will carry much influence within the clinical community. Therefore, this paper is likely to influence healthcare recommendation and prescribing patterns.  


What does the data mean for healthcare professionals?

Combined with the vast amount of previously published material linking NSAIDs with increased cardiovascular risk, the Kearney paper reinforces the need for a rational approach to the recommending and prescribing of analgesics. These data show that those with CHF, a history of hypertension, those being treated for hypertension and the elderly are at particular risk of NSAID-related CVD events. This information is likely lead to recommendations on which analgesics should be recommended for certain patient types. Indeed, as summarised in the table below, experts are already starting to release such recommendations into the medical press.


Guidance on analgesic use in cardiovascular conditions

Patient characteristics




Recommend paracetamol, unless contraindicated.12, 17

Cardiovascular disease

Recommend paracetamol, unless contraindicated12, 18

Receiving low dose aspirin

Paracetamol or NSAIDs, however consider potential additive gastrointestinal effects of the latter11


Risk of cardiorenal effects of NSAIDs increases with age, therefore monitoring for early onset of oedema, de-stabilisation of blood pressure control and/or onset of congestive heart failure should be undertaken.12


Consider also potential drug-drug interactions with NSAIDs and anti-hypertensive and anticoagulant medication

Recommend paracetamol, unless contraindicated.12


  1. FDA issues public health advisory on Vioxx as its manufacturer voluntarily withdraws the product. FDA News. Released September 30 2004. Accessed at : Accessed on: June 02 06.
  2. Juni P, Nartey L, Reichenbach S, Sterchi R, Dieppe PA, Egger M. Risk of cardiovascular events and rofecoxib: cumulative meta-analysis. Lancet 2004;364(9450):2021-9.
  3. Solomon SD, McMurray JJ, Pfeffer MA, Wittes J, Fowler R, Finn P, et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 2005;352(11):1071-80.
  4. Hippisley-Cox J, Coupland C. Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis. Bmj 2005;330(7504):1366.
  5. Simmons DL, Botting RM, Hla T. Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol Rev 2004;56(3):387-437.
  6. Page J, Henry D. Consumption of NSAIDs and the development of congestive heart failure in elderly patients: an underrecognized public health problem. Arch Intern Med 2000;160(6):777-84.
  7. Huerta C, Varas-Lorenzo C, Castellsague J, Garcia Rodriguez LA. Nonsteroidal anti-inflammatory drugs and risk of first hospital admission for heart failure in the general population. Heart 2006.
  8. Merlo J, Broms K, Lindblad U, Bjorck-Linne A, Liedholm H, Ostergren PO, et al. Association of outpatient utilisation of non-steroidal anti-inflammatory drugs and hospitalised heart failure in the entire Swedish population. Eur J Clin Pharmacol 2001;57(1):71-5.
  9. Heerdink ER, Leufkens HG, Herings RM, Ottervanger JP, Stricker BH, Bakker A. NSAIDs associated with increased risk of congestive heart failure in elderly patients taking diuretics. Arch Intern Med 1998;158(10):1108-12.
  10. Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ 2006;332:1302-1308.
  11. Gaziano JM, Gibson CM. Potential for drug-drug interactions in patients taking analgesics for mild-to-moderate pain and low-dose aspirin for cardioprotection. Am J Cardiol 2006;97(9A):23-9.
  12. Whelton A. Clinical implications of nonopioid analgesia for relief of mild-to-moderate pain in patients with or at risk for cardiovascular disease. Am J Cardiol 2006;97(9A):3-9.
  13. Pope JE, Anderson JJ, Felson DT. A meta-analysis of the effects of nonsteroidal anti-inflammatory drugs on blood pressure. Arch Intern Med 1993;153(4):477-84.
  14. Johnson AG, Simons LA, Simons J, Friedlander Y, McCallum J. Non-steroidal anti-inflammatory drugs and hypertension in the elderly: a community-based cross-sectional study. Br J Clin Pharmacol 1993;35(5):455-9.
  15. Kurth T, Glynn RJ, Walker AM, Chan KA, Buring JE, Hennekens CH, et al. Inhibition of clinical benefits of aspirin on first myocardial infarction by nonsteroidal antiinflammatory drugs. Circulation 2003;108(10):1191-5.
  16. MacDonald TM, Wei L. Effect of ibuprofen on cardioprotective effect of aspirin. Lancet 2003;361(9357):573-4.
  17. Gaziano JM. Nonnarcotic Analgesics and Hypertension. Am J Cardiol 2006;97(9S1):10-1
  18. Hillis WS. Areas of emerging interest in analgesia: cardiovascular complications. Am J Ther 2002;9(3):259-69.


Additional Info

  • TheSynapse Magazines: 2006
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