In another study of prior PPI use and its effects on magnesium levels among 11,490 intensive care unit admissions, Danziger and colleagues found that the association of PPI use and hypomagnesemia was limited to patients who concomitantly received a diuretic, and use of a histamine 2 receptor antagonist was not associated with hypomagnesemia.3 A third cross-sectional study of 402 adults with hypomagnesemia on hospital admission found no association between outpatient PPI regimens and hypomagnesemia.5 Other studies designed to investigate PPI-associated hypomagnesemia were limited by short-term PPI use, small samples, concurrent diseases, and confounding variables (eg, history of alcoholism).6,7
Need for Present Study
The evidence needed to establish the incidence of PPI-associated hypomagnesemia is limited. Hypomagnesemia can lead to serious AEs, as just outlined, and is a common indication for hospitalization.8 The hypomagnesemia rate is about 12% in hospitalized patients and sharply higher (60%-65%) in those who are critically ill. Proton pump inhibitor-associated hypomagnesemia is preventable, and monitoring parameters can be recommended to patients undergoing long-term therapy.
Ajumobi and colleagues found that 13,713 (23.4%) of 58,605 patients treated at a VA center over a 12-month period were receiving a PPI.9 Gawron and colleagues found that many veterans had been prescribed a PPI and were receiving high total daily doses for the treatment of gastroesophageal reflux disease.10 The majority of patients received a 90-day or longer supply and showed minimal evidence of step-down therapy or cessation of PPI therapy.
In the present study, the authors investigated the rate of PPI-associated hypomagnesemia in a veteran population at a facility where the majority of PPIs were by prescription, not OTC. The Captain James A. Lovell Federal Health Care Center (FHCC) is a combined DoD and VA facility where veterans and active military members and their dependents receive medical care and prescription drugs.
This study’s primary objective was to determine the rate of PPI-induced hypomagnesemia. The secondary objective was to identify any clinical factors (eg, PPI dose and therapy duration, concomitant use of a diuretic) that might further increase the risk of hypomagnesemia.
Methods
After the study protocol was approved by the Lovell FHCC institutional review board, the authors retrospectively compared patients with a low magnesium level (case group) with patients with a normal magnesium level (control group). In each group, the authors identified patients who underwent PPI therapy and those who did not (Figure).
Study inclusion criteria were low magnesium level (< 1.8 mg/dL) within the past 5 years for veterans in the case group and normal magnesium level (1.8-2.4 mg/dL) within the past 5 years for veterans in the control group. Exclusion criteria were nonveterans and no prior magnesium level for a veteran.
Patients were assigned in a ratio of 1 (case group) to 4 (control group) and were added only after confirmation that multiple magnesium levels had been recorded (January 2008-January 2013).