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 Recommendations
Hypertension 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


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