Long-Term Use of Proton-Pump Inhibitors: Unravelling the Safety Puzzle

Globally, over 25% of the population suffers from acid-related disorders such as dyspepsia or gastroesophageal reflux disease (GERD), and around 7.6% of Indians report having GERD symptoms on a frequent enough basis to warrant a diagnosis. Over the past three decades, proton-pump inhibitors (PPIs) have been the mainstay of medical therapy for acid-peptic diseases like GERD, etc. Additionally, they are frequently prescribed for prophylactic purposes and in conjunction with non-steroidal anti-inflammatory drugs. PPIs are generally prescribed for four to eight weeks. However, it may be prescribed for patients with comorbidities and multiple medications for a longer period of time. While this remains true in terms of effectiveness, concerns have been raised about the safety of long-term PPI use and the serious adverse effects that may result. Some of the observational and population-based cohort studies have shown an association between long-term use of PPIs and an increased risk of pneumonia, major cardiovascular events, dementia, vitamin B12 deficiency, bone fractures, gastric cancer, and kidney injury, among others. This review analyzes the clinical data supporting the long-term use of PPIs and takes a deep dive into whether these several emerging long-term concerns apply to the currently available PPIs in India. We have summarized a vast array of studies, including randomized trials, cohort studies, and meta-analyses, that report low or high incidences of major health risks linked with PPIs and have assessed their appropriateness over a given period.