Big Data Study Suggests Heart Attack Risk Linked to Common Heartburn Medications

Some researchers at Stanford University in the United States used electronic health records to test the following hypothesis:Is there a potential link between heart attacks and this class of drugs commonly used to treat heartburn?This class of drugs, also known as proton pump inhibitors (PPIs), primarily includes omeprazole (Prilosec) and esomeprazole (Nexium). The research team stated that,The purpose of studying this topic is to demonstrate the utility of applying big data to electronic health records.Furthermore, they stated that further research is needed to determine whether there is a link between them.

In the initial trial run, researchers used an advanced computer program to extract electronic health records and patient information from Stanford University School of Medicine’s data scientists and medical investigators. After processing and analysis, they found thatThis class of drugs commonly used to treat heartburn may increase the risk of heart attack.

According to Nigam Shah, a biomedical informatics expert at Stanford University and head of the research team, preliminary findings suggest that data mining could become a highly valuable tool for identifying potential drug safety issues from real-world data on patient responses to medications. Currently, pharmaceutical companies and the U.S. Food and Drug Administration (FDA) primarily rely on rigorously controlled clinical trials to evaluate drugs before approving them for production and market entry. This technology—data mining—may one day serve as a complement to these stringent review processes.

In his recent study published in PLOS One, a renowned academic journal, Nigam Shah reiterated that relevant authorities should conduct more rigorous reviews of a common class of medications used to treat heartburn, primarily proton pump inhibitors (PPIs) such as esomeprazole (Nexium) and omeprazole (Prilosec). Last year, researchers from National Yang-Ming University in Taiwan reported that their investigation found an additional case of myocardial infarction for every 4,357 patients who took proton pump inhibitors for two weeks, compared with patients who did not take these medications.

However, the greater significance of Nigam Shah’s research lies in its demonstration of a computer application that leverages natural language processing to scan hundreds of thousands of electronic health records (EHRs) and extract key terms and phrases. Under regulations issued by the Obama administration, starting this year, all healthcare providers are required to use EHRs when diagnosing patients covered by Medicare. These records provide a wealth of data on patients’ prior medical conditions, such as surgical histories and medication usage. In practice, however, few researchers have been able to identify effective methods for utilizing this data.

In one of the initial test runs of this new program, Nigam Shah’s research team analyzed the health records of 3 million patients to validate the previously proposed hypothesis regarding whether there is an association between proton pump inhibitors and the risk of heart attack.Analysis revealed a slight increase in the risk of heart attack among patients after initiating this class of medications. Nicholas Leeper, a surgeon at Stanford University School of Medicine, described this effect as a “relatively modest increase.”

Since this study only involves health records, further clinical studies on patients are necessary to confirm the existence of this association. However,Investigations into the second major class of drugs used to treat heartburn, known as H2-receptor antagonists (H2 blockers), such as Zantac and Tagamet, have revealed no association with the aforementioned correlations.More than 100 million prescriptions for proton pump inhibitors (PPIs) are written annually, as healthcare professionals consider this class of drugs to be more effective than H2-receptor antagonists. This drug category generates $14 billion in annual sales. PPIs entered the U.S. market in 1989 and were approved for over-the-counter use in 2003.

Bill Howe, a data analytics expert at the University of Washington’s eScience Institute, stated that this demonstration effectively hints at the future possibility of integrating Stanford-style plans with human trials to screen for drug safety issues. However, he also pointed out a limitation in Nigam Shah’s study: the failure to control for obesity, a variable that can both cause heartburn and serve as a risk factor for heart disease.

To demonstrate the safety and efficacy of a drug, pharmaceutical companies must undergo a series of clinical trials supervised by the U.S. Food and Drug Administration (FDA). These trials can readily capture immediate and acute side effects of a medication, such as diarrhea and loss of appetite. However, once a drug is launched onto the market, subtle or long-term adverse effects associated with its use become difficult to detect. External teams typically lack access to electronic health records (EHRs) available to healthcare providers, which could offer clues that alert pharmaceutical companies or the FDA to potential drug safety concerns.

“Disappointingly, hospitals and health systems often have little incentive to screen for and remove substandard medications,” said Nigam Shah. “Pharmaceutical companies and the FDA should be vigilant about substandard drugs, but they lack access to electronic health records.” In the United States, adverse drug events (ADEs)—defined as harmful outcomes following medication use, including complications and side effects—result in 2 million cases of injury, hospitalization, and death annually, with associated medical costs exceeding $75 billion.

This new application is not limited to detecting adverse reactions. For example, a male patient scheduled for prostate surgery who is concerned about the risk of postoperative erectile dysfunction can use a version of this system to compare outcomes among men who have undergone the same procedure at different hospitals or performed by different surgeons, thereby assessing the incidence and probability of erectile dysfunction. Physicians can also log into the system to identify which medications demonstrate the best efficacy in patient populations that are not adequately represented in clinical trials.

Nigam Shah stated, “The data are right there, lying within electronic health records. Given that, why not leverage them?” The FDA had issued a warning regarding a drug called cilostazol; however, Nigam Shah’s research team challenged this stance. Their analysis of relevant data indicated that the risks associated with cilostazol were far lower than previously believed.

Nigam Shah, who holds dual PhDs in medicine and informatics, does not recommend discontinuing any medication without consulting a professional physician. After designing this computer program in 2013, his research team conducted tests on it. The results showed that the program had an error rate of 15%. Nevertheless, he still stated that the results calculated by the program could at least provide physicians and patients with a reason to pause before initiating treatment for heartburn, allowing them to consider their unique circumstances and comprehensively evaluate all possible treatment options.

Nigam Shah stated, “At the very least, if you have purchased a proton pump inhibitor (PPI) over the counter without a physician’s prescription and have taken it for 14 days (the recommended treatment duration indicated on the packaging), and your physician is unaware of your use of this medication, you must inform them.”

Next, he will focus on two things: first, making minor adjustments to the software’s precision; and second, raising funds for an experiment designed to accurately determine whether proton pump inhibitors actually increase the risk of heart disease.

In response to the study, Procter & Gamble, which markets omeprazole (Prilosec), cited a statement issued by Barb Kochanowski, Vice President of Regulatory and Scientific Affairs at the Consumer Healthcare Products Association. The statement read: “Millions of consumers rely on proton pump inhibitors to relieve their frequent heartburn symptoms. As with all over-the-counter medications, consumers should carefully read the drug label and strictly follow the usage instructions when using proton pump inhibitors. This is intended to ensure a thorough understanding of the drug’s indications, as well as to guarantee appropriate dosing and avoid drug interactions. Additionally, if severe or persistent symptoms occur after taking the medication, patients should immediately report this to their healthcare provider.”

Michele Meixell, head of external communications at AstraZeneca, the marketer of esomeprazole (Nexium), wrote in an email: “Patient safety is AstraZeneca’s top priority. We believe that all our products, including esomeprazole (Nexium), i.e., esomeprazole magnesium, are generally safe and effective when taken strictly in accordance with the prescribing information. This has been validated by human data studies and more than a decade of clinical use.”

Compiled by Lü Xiaoyi | Edited by Mo Renying