Drug dilemma: the risks of PPIs

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Drug dilemma: the risks of PPIs Fracture risk: o The absolute risk increase is small (0.5 extra hip fractures/1000 person years in regular PPI users compared with non-users) AND WAS ONLY SEEN IN SMOKERS (and women this was from the US nurses health study!) (BMJ 2012;344:e372). o Risk is duration dependent: the longer you take the PPI for (>12m), the greater the risk. o The mechanism isn t clear, although several theories have been suggested, including reducing calcium absorption or interfering with osteoclast function. Infections o Increased risk of Clostridium difficile infection (Arch Intern Med 2010;170: 784 and 772) and recurrent C. difficile (JAMA Intern Med. 2017; 177(6):784). o Early data suggested an increased risk of pneumonia but subsequent studies have disproved this (JAMA 2009; 301:2120, Ann Intern Med 2008;149:391, BMJ 2016;355:i5813). Dementia: there is an association (not causation) between dementia and regular PPI use. The risk increase is small: 1.4x increased risk (HR 1.44, CI 1.4-1.5) (DTB 2016:54;65). Chronic kidney disease: again, this is an association only and more research is needed (DTB 2016:54;39). CVD: there is some evidence, gleaned from pharmacovigilance data that has suggested a small increase in the risk of MI in those on PPIs (<1.2x increase risk of MI and 2 fold increased risk of CV death after 5 years PPI use). This data must not be over interpreted and should not change our practice more data is needed before we change our practice on the basis of this study! (PLoS One 10 Jun 2015, doi:10.1371/journal.pone.0124653). Hypomagnesium: this association (based on 38 case reports to the US FDA!) triggered an MHRA alert suggesting we consider measuring magnesium levels before treatment in those likely to be on long-term treatment. However, our understanding of the link between the two, its clinical significance and how to manage it, is severely lacking (Drug Safety Update, April 2012) What about H2RA for gastroprotection? There are no good trials we are aware of that demonstrate H2RA are effective for gastroprotection in those on anti-platelet agents/anticoagulants. Do PPIs affect aspirin efficacy? A study of patients in Denmark looked at people admitted with a first MI. They matched those given a PPI as well as aspirin (>4000 patients) with those given aspirin but not PPI (15 000 people) (BMJ 2011;342:d2690). Those given a PPI and aspirin were at increased risk of re-infarction compared to those not given a PPI. The risk increase was small. All PPIs seemed to have the same effect (although rabeprazole was excluded as too few people were taking it). H2RA did not increase the risk of re-infarction. None were on clopidogrel. Why? Several suggestions have been made: Changing the acidity of the stomach may affect aspirin absorption. PPIs may interfere with aspirin s ability to interact with platelets. What does this mean in practice? At the moment the risk increase is small and has not been quantified compared to the benefits of gastroprotection. There are no recommendations that we should stop using PPIs with aspirin, but I suggest we use them only where there is a good reason, until we know more. We make every effort to ensure the information in these pages is accurate and correct at the date of publication, but it is of necessity of a brief and general nature, and this should not replace your own good clinical judgement, or be regarded as a substitute for taking professional advice in appropriate circumstances. In particular check drug doses, side effects and interactions with the British National Formulary. Save insofar as any such liability cannot be excluded at law, we do not accept any liability for loss of any type caused by reliance on the information in these pages. GP Update Limited June 2017

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