Proton-Pump Inhibitors Reduce Bleeding Risk in Antiplatelet Therapy

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Nadir Platelets AKI Cardiopulmonary Bypass Surgery
The risk for major bleeding while taking antiplatelet therapy significantly increased with age.

Results of a population-based cohort study published in the Lancet demonstrated high rates of major bleeding in patients taking antiplatelet medications without a coprescribed proton pump inhibitor (PPI).1

Approximately 50% of adults aged 75 years or older who take antiplatelet drugs daily do so for secondary prevention of vascular disease, as recommended by American Heart Association/American Stroke Association Guidelines.2,3 Although antiplatelet medications are associated with an increased risk for major bleeding, most commonly for gastrointestinal bleeding, PPIs have been found to reduce this risk substantially.4

Despite this benefit, PPIs are not routinely prescribed with antiplatelet drugs, and recommendations for the use of PPIs are not included in professional guidelines pertaining to secondary prevention of vascular events. This could be because of reports of adverse effects linked to PPIs, such as enteric infections, and possibly because of low fatalities associated with upper gastrointestinal bleeds in aspirin trials, generally not thought to cause permanent disability.5,6  

Noting the need to determine “reliable estimates of age-specific risks and consequences of bleeding in a real-world setting,” the researchers investigated links between these variables and upper gastrointestinal bleeding associated with antiplatelet therapy after vascular events.

Of the total sample of 3166 patients (50% aged ≥75 years), 405 experienced first bleeding events during follow-up (n=218 gastrointestinal, n=45 intracranial, and n=142 other) during 13,509 patient-years of follow-up; 78% (n=314) of these patients were admitted to the hospital. The risk for major bleeding increased significantly with age (≥75 years hazard ratio [HR], 3.10; 95% CI, 2.27-4.24; P <.0001), especially the risk for fatal bleeds (HR, 5.53; 95% CI, 2.65-11.54; P <.0001).

Gastrointestinal bleeding also increased with age, especially disabling or fatal bleeds (HR, 10.26; 95% CI, 4.37-24.13; P <.0001). In patients aged 75 years or older, major upper gastrointestinal bleeds were more often disabling or fatal compared with recurrent ischemic stroke, and occurred more frequently than disabling or fatal intracerebral hemorrhage (absolute risk, 9.15 per 1000 patient-years; 95% CI, 6.67-12.24).

These findings suggest that 75 years may be an appropriate point at which to begin PPI therapy both in patients who are newly initiated on antiplatelet drugs and in patients receiving established treatment.

“More research is still required into how best to identify patients at high risk of bleeding, how to reduce the risk of non-upper gastrointestinal bleeds, and into the overall balance of risks and benefits of long-term antiplatelet treatment at older ages in both primary and secondary prevention,” the researchers concluded.

Dr Rothwell reports that he has received fees from Bayer. The remaining researchers declare they have no conflicts of interest.

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1. Li L, Geraghty OC, Mehta Z, Rothwell PM, on behalf of the Oxford Vascular Study. Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort study [published online June 13, 2017]. Lancet. doi:10.1016/S0140-6736(17)30770-5

2. Williams CD, Chan AT, Elman MR et al. Aspirin use among adults in the U.S. Results of a national survey. Am J Prev Med. 2015;48:501-508. doi:10.1016/j.amepre.2014.11.005

3. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:2160-2236. doi:10.1161/STR.0000000000000024

4. Mo C, Sun G, Lu ML, et al. Proton pump inhibitors in prevention of low-dose aspirin-associated upper gastrointestinal injuries. World J Gastroenterol 2015;21:5382-5392. doi: 10.3748/wjg.v21.i17.5382

5. Moayyedi P, Leontiadis GI. The risks of PPI therapy. Nat Rev Gastroenterol Hepatol. 2012;9:132-139. doi:10.1038/nrgastro.2011.272

6. Rothwell PM, Price JF, Fowkes FG, et al. Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet. 2012;379:1602-1612. doi:10.1016/S0140-6736(11)61720-0