PPI therapy

An important consideration prior to the start of PPI therapy in any patient is the potential of detrimental effects. According to several studies, prescription of PPIs is inappropriate in 40% to 80% of individuals.³³ Proton pump inhibitors can cause adverse drug effects, such as abdominal pain, nausea, diarrhea and constipation. In addition, they have been associated with a variety of other adverse events, including fundic gland polyps secondary to hypergastrinemia,³⁴ hypomagnesemia, hypocalcemia, bone fractures,^35,36 decreased absorption of vitamin B12,³⁷ diarrhea,³⁸ and pneumonia,³⁹though evidence for the clinical significance of these relationships is limited. Importantly, a landmark data-mining study published in 2015 concluded that GERD patients treated with PPI have an increased association with myocardial infarction⁴⁰and a 2-fold increase in association with cardiovascular mortality on survival analyses. Dementia⁴¹and stroke⁴² have also been linked to PPI use.

A recent study suggested that medical error is currently the third leading cause of death in the United States.⁴³ Drug reactions and interactions account for a considerable percentage of these deaths. Proton pump inhibitors have several purported interactions with other medications, the most widely studied of which are clopidogrel and methotrexate.^44,45 Thus, for an individual patient, it is pertinent to address the indication of use and balance the risks and benefits of therapy.