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Long-term PPI usage may be associated with an increase in cardiovascular risk

The study

Data from 2.9 million patients was ‘mined’ and reviewed to examine whether PPI usage was associated with cardiovascular risk in the general population.

The findings

1 Patients suffering from GORD who took PPIs had a 16% higher risk of having an MI.

2 General mortality from cardiovascular disease was also significantly higher in patients taking PPIs.

3 These associations exist irrespective of age and whether or not the patients were taking clopidogrel (clopidogrel is specifically highlighted as the FDA issued a warning about a possible interaction between PPIs and clopidogrel due to concerns that PPIs may impede the conversion of clopidogrel into its active form).

4 H2 blockers (such as ranitidine) were not found to be associated with a higher risk of MI.

What this means for GPs

This study suggest that PPIs may possibly be associated with an increased risk of MI, whilst H2 blockers are not.

GPs should be judicious and consider the risks and benefits of PPIs before prescribing them, and should consider the use of H2 blockers as an alternative.

The authors cite a number of possible theories for this association. One significant theory is that PPIs may impede dimethylargininase activity, which ultimately leads to less nitric oxide (this plays a vital role in the homeostasis of the vascular system).

On the other hand, the authors accept that ‘these observational data may be subject to confounding in multiple ways, and it is possible that PPI usage is merely a marker of a sicker patient population’ and that ‘a prospective randomised study in the general population (inclusive of both lean and obese individuals) is required before changing clinical practice’.

However, the fact that H2 blockers were not associated with an increased mortality suggest that a specific association of cardiovascular risk increase with PPIs may well exist – this is particularly relevant as PPIs are very widely used, and are also available over the counter (eg nexium).

The paper

PLOS (Public Library of Science) June 2015

Dr Hamed Khan is a GP in the emergency department of St George’s, London, and a clinical lecturer. He tweets as @drhamedkhan.