The Problem With PPIs

Most of us can recall medical innovations that fundamentally changed the way we practice and prescribe. Important revolutions do not need to be dramatic, such as the discovery and widespread use of low-molecular-weight heparin or the MRI, for us to be forever converted. For me, it was the discovery and widespread use of proton pump inhibitors (PPIs).

In the 1970s, evidence emerged that the proton pump in stomach parietal cells was the last step in acid secretion. At the same time, preanesthetic screenings pointed to the antisecretory effects of a compound called timoprazole. Creative chemistry and side-chain substitutions led to the launch of omeprazole in 1990. The rest, as they say, is history.

PPIs are currently the third most commonly sold drugs in the Unite States, in large part because they transformed the care of patients with gastroesophageal reflux disease and dyspepsia in a remarkable way.

In the early days, clinicians seemed inclined to start patients on the histamine receptor antagonists as first-line therapy, reserving PPIs for more recalcitrant cases. With time, however, clinicians reached for PPIs earlier in the course of therapy to more quickly eradicate symptoms. As the obesity epidemic spread, so too did the epidemic of GERD and PPI use.

What we seem to have lost sight of is that patients are being continued on these medications indefinitely. But at what risk?

Dr. Neena S. Abraham of Veterans Affairs Medical Center in Houston, and her colleagues, recently reviewed the literature on the long-term adverse health consequences of PPI use. She reported that the strongest evidence supports an increased risk for the development of Clostridium difficile infection and bone fracture. The mechanism of bone fracture relates to acid suppression and the "triple effect" of impairing the absorption of vitamin B₁₂, which decreases osteoblastic activity; decreasing calcium absorption; and hypergastrinemia, which increases the release of parathyroid hormone contributing to bone resorption (Curr. Opin. Gastroenterol. 2012 [Epub ahead of print])

Dr. Abraham challenges us to prescribe PPIs only for "robust indications." We need to challenge ourselves to take the time to try tapering or discontinuation trials among patients who have been on them for a prolonged period of time. Informing patients of the long-term risks will arm us for what might be, with many patients, difficult discussions.

Jon O. Ebbert, M.D., is professor of medicine and primary care clinician at the Mayo Clinic in Rochester, Minn. He reports having no conflicts of interest. The opinions expressed are solely those of the author.

Most of us can recall medical innovations that fundamentally changed the way we practice and prescribe. Important revolutions do not need to be dramatic, such as the discovery and widespread use of low-molecular-weight heparin or the MRI, for us to be forever converted. For me, it was the discovery and widespread use of proton pump inhibitors (PPIs).

In the 1970s, evidence emerged that the proton pump in stomach parietal cells was the last step in acid secretion. At the same time, preanesthetic screenings pointed to the antisecretory effects of a compound called timoprazole. Creative chemistry and side-chain substitutions led to the launch of omeprazole in 1990. The rest, as they say, is history.

PPIs are currently the third most commonly sold drugs in the Unite States, in large part because they transformed the care of patients with gastroesophageal reflux disease and dyspepsia in a remarkable way.

In the early days, clinicians seemed inclined to start patients on the histamine receptor antagonists as first-line therapy, reserving PPIs for more recalcitrant cases. With time, however, clinicians reached for PPIs earlier in the course of therapy to more quickly eradicate symptoms. As the obesity epidemic spread, so too did the epidemic of GERD and PPI use.

What we seem to have lost sight of is that patients are being continued on these medications indefinitely. But at what risk?

Dr. Neena S. Abraham of Veterans Affairs Medical Center in Houston, and her colleagues, recently reviewed the literature on the long-term adverse health consequences of PPI use. She reported that the strongest evidence supports an increased risk for the development of Clostridium difficile infection and bone fracture. The mechanism of bone fracture relates to acid suppression and the "triple effect" of impairing the absorption of vitamin B₁₂, which decreases osteoblastic activity; decreasing calcium absorption; and hypergastrinemia, which increases the release of parathyroid hormone contributing to bone resorption (Curr. Opin. Gastroenterol. 2012 [Epub ahead of print])

Dr. Abraham challenges us to prescribe PPIs only for "robust indications." We need to challenge ourselves to take the time to try tapering or discontinuation trials among patients who have been on them for a prolonged period of time. Informing patients of the long-term risks will arm us for what might be, with many patients, difficult discussions.

Jon O. Ebbert, M.D., is professor of medicine and primary care clinician at the Mayo Clinic in Rochester, Minn. He reports having no conflicts of interest. The opinions expressed are solely those of the author.

Most of us can recall medical innovations that fundamentally changed the way we practice and prescribe. Important revolutions do not need to be dramatic, such as the discovery and widespread use of low-molecular-weight heparin or the MRI, for us to be forever converted. For me, it was the discovery and widespread use of proton pump inhibitors (PPIs).

In the 1970s, evidence emerged that the proton pump in stomach parietal cells was the last step in acid secretion. At the same time, preanesthetic screenings pointed to the antisecretory effects of a compound called timoprazole. Creative chemistry and side-chain substitutions led to the launch of omeprazole in 1990. The rest, as they say, is history.

PPIs are currently the third most commonly sold drugs in the Unite States, in large part because they transformed the care of patients with gastroesophageal reflux disease and dyspepsia in a remarkable way.

In the early days, clinicians seemed inclined to start patients on the histamine receptor antagonists as first-line therapy, reserving PPIs for more recalcitrant cases. With time, however, clinicians reached for PPIs earlier in the course of therapy to more quickly eradicate symptoms. As the obesity epidemic spread, so too did the epidemic of GERD and PPI use.

What we seem to have lost sight of is that patients are being continued on these medications indefinitely. But at what risk?

Dr. Neena S. Abraham of Veterans Affairs Medical Center in Houston, and her colleagues, recently reviewed the literature on the long-term adverse health consequences of PPI use. She reported that the strongest evidence supports an increased risk for the development of Clostridium difficile infection and bone fracture. The mechanism of bone fracture relates to acid suppression and the "triple effect" of impairing the absorption of vitamin B₁₂, which decreases osteoblastic activity; decreasing calcium absorption; and hypergastrinemia, which increases the release of parathyroid hormone contributing to bone resorption (Curr. Opin. Gastroenterol. 2012 [Epub ahead of print])

Dr. Abraham challenges us to prescribe PPIs only for "robust indications." We need to challenge ourselves to take the time to try tapering or discontinuation trials among patients who have been on them for a prolonged period of time. Informing patients of the long-term risks will arm us for what might be, with many patients, difficult discussions.

Jon O. Ebbert, M.D., is professor of medicine and primary care clinician at the Mayo Clinic in Rochester, Minn. He reports having no conflicts of interest. The opinions expressed are solely those of the author.