Proton Pump Inhibitors, Anticoagulants May Be Linked to Iron Deficiency Anemia

Credit: Unsplash / Michał Parzuchowski

Longterm exposure to proton pump inhibitors (PPIs) and oral anticoagulants (OACs) was independently linked to a higher risk of iron deficiency anemia development, according to a recent study.

However, the investigative team from the Poole Hospital NHS Foundation trust did note that longterm treatment with anti-platelet therapies, antidepressants, or non-steroidal anti-inflammatory drugs (NSAIDs) were not linked to a higher risk of developing IDA.

“While association does not prove causation, the findings could potentially influence prescribing practice, particularly of PPIs in those with unexplained recurrent IDA,” wrote the investigative team.

IDA remains a critical global healthcare issue. It is primarily caused by a reduction in assimilation or enhanced iron loss, with many cases of IDA having been linked to an underlying cause in the upper or lower gastrointestinal (GI) tract. However, the majority of cases remain unexplained.

Elderly patients, taking frequent medications, are typically referred for further investigation on how these medications may contribute to IDA development. Multiple therapies could influence iron balance in the GI tract and potentially elevate the risk of IDA development.

However, few published studies with confirmatory evidence exist on the relevance of long-term therapy with OACs, anti-platelet agents, and PPIs on the pathogenesis of IDA, with little evidence for NSAIDs and antidepressants. With the lack of clear guidance, investigators stressed the need for further research for a comprehensive systematic review of this relationship.

A personal electronic healthcare database generated in primary care, and collecting individual repeat prescription lists, was used to determine exposure to each class of medication among a cohort of patients with IDA.

For each medication demonstrating significance, models were used to determine risk differences between those in the IDA cohort with or without hemorrhagic lesions after investigation.

After exclusions for incomplete data, there were 409 subjects in the IDA cohort and 801 in the control cohort included for analysis. Across both populations, drug exposure was identified in 157 (13.0%) for OACs, 202 (16.7%) for antidepressants, 205 (16.9%) for anti-platelet agents, 574 (47.4%) for PPIs, and 52 (4.3%) for NSAIDs.

Analysis showed the presence of multiple relationships between study variables, including notably strong associations between the prescription of PPIs and OACs, and antiplatelet and non-steroidal anti-inflammatories.

Statistical assessment in the model revealed a strong association between long-term PPI exposure and IDA risk, as well as a statistically significant association between long-term OAC exposure and IDA risk.

Meanwhile, IDA was negatively associated with short-term antidepressant exposure, but not long-term therapy. No associations were identified between IDA and anti-platelet or non-steroidal anti-inflammatory exposure of any duration.

Investigators indicated the association with IDA and OACs was predominantly apparently in individuals with underlying hemorrhagic lesions in the GI tract. By contrast, the association between IDA and PPIs was independent of hemorrhagic lesion status.

“The major conclusions of this study are that anti-platelet therapy does not contribute to the development of IDA, long-term anticoagulation has a modest influence, and the largest effect appears to be exerted by long-term PPI therapy,” they wrote.

An original version of this article was published on sister site HCPLive.