Proton pump inhibitors are one of the most commonly prescribed drugs, but patients are 16%-21% more likely to suffer a heart attack, study suggests

Common heartburn drugs could increase the risk of heart attacks, scientists have warned. A major US study drawing on the health records of nearly three million patients showed that people taking indigestion drugs called proton pump inhibitors were 16 to 21% more likely to suffer a heart attack.

Nick Leeper, a cardiologist at Stanford University in California, who led the investigation, said: “At first glance you may think a 16% increase in risk is modest and say what’s the big deal? But heart disease is by far the leading cause of death in the western world and PPIs are so commonly prescribed. This is potentially a big deal from a public health perspective.”



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There are around eight million prescriptions for PPI drugs, such as lansoprazole and omeprazole, in the UK each year, although the drugs are available over-the-counter in chemists and in supermarkets meaning the exact number of people taking them is not known.

However, Dr Leeper cautioned that patients should not stop taking the medication on the basis of the findings – not least because the study could not definitively prove the drugs were causing the heart attacks. An alternative explanation was that patients taking the drugs were simply sicker than those in the control groups, which were made up of people with heartburn who were not on medication as well as those taking other types of indigestion pills.

“We have not proved causation,” said Dr Leeper. “But it’s a very worrisome association and for now we want people to discuss the risks and benefits with their physicians.”

Marc Dweck, a cardiologist at the University of Edinburgh who was not involved in the research, pointed out that for many patients heartburn can be a sign of more serious gastrointestinal problems rather than just being a minor source of irritation after meals. “Stopping the PPI may be dangerous given that it is likely to have been prescribed to stop bleeding,” he said. “Bleeding in the context of a recent heart attack is a dangerous combination. Stopping a drug that prevents this in high risk patients is therefore potentially a problem.”

Mette Charlot, a cardiologist at the Copenhagen University Hospital Gentofte, said the findings added to previous evidence suggesting a possible link between heartburn medicines and heart disease, but agreed that current guidelines should not yet be changed. “We also know that angina can mimic the symptoms of heart burn and it is possible that misdiagnosed patients can explain the increase in risk,” she said. “My main concern is that if patients stop relevant treatment with PPI they increase their risk of a gastrointestinal bleeding. And we do know that gastrointestinal bleeding increases the risk of a heart attack and can increase mortality.

PPI drugs are taken about an hour before a meal and work by blocking the actions of cells called proton pumps, which produce stomach acid. This lowers the acidity of liquid from the stomach and prevents the burning sensation in the throat.

However, the scientists believe that they may also interfere with the production of nitric oxide in the bloodstream, which helps prevent the accumulation of plaque in vessels. Previous research in animals and cell cultures showed that PPIs led to a drop in the level of nitric oxide, causing vessels to narrow and inflame.

In the latest study, published in the journal PLOS One, scientists trawled two separate sets of medical records, covering a total of 2.9 million patients, including around 300,000 who had diagnosed acid reflux (heartburn). This group included patients who were not taking medication, those who had been prescribed PPIs and also patients prescribed another class of drug, called H2 blockers.

The data suggested that those who had used PPIs were 16 to 21% more likely to have suffered a major cardiovascular event, such as a heart attack. The study took into account other risk factors such as age, gender, smoking, diabetes and blood pressure. No association was seen for patients on the H2 drugs, which the researchers said added to their confidence that the PPIs were causing the added risk.

“Our report raises concerns that these drugs, which are available over the counter and are among the most commonly prescribed drugs in the world, may not be as safe as we previously assumed,” said Dr Leeper.