Proton Pump Inhibitors May Cause Ischemic Strokes and Other Serious Conditions

They're among the most commonly prescribed drugs for heartburn, but proton pump inhibitors (PPIs) have been linked to ischemic stroke and other risks.

proton pump inhibitors

Proton pump inhibitors (PPIs) have been linked to risk of ischemic stroke, the most common type of stroke. It is caused by insufficient blood flow to the brain.

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Proton pump inhibitors (PPIs) are prescribed to some 15 million Americans to reduce stomach acid and ease heartburn. Millions more use over-the-counter PPIs. New research, however, is showing a link between long-term, high-dosage PPI use and ischemic stroke.

An ischemic stroke is the most common type of stroke and is caused by insufficient blood reaching part of the brain. The blockage could be caused by a blood clot in an artery leading to the brain or by an embolus that is formed elsewhere and carried to the brain.

Proton Pump Inhibitors: Issues to Consider

Stroke is not the only concern regarding the use of PPIs. Studies have indicated an association between proton pump inhibitors and kidney damage, dementia, infection, fractures, and heart attack.

The mechanism by which PPIs may damage the body’s organs or systems is unknown, but theories include altering the environment of the gut, affecting the absorption of vitamins and minerals, and changing the way drugs interact with each other.

Recent findings are understandably disturbing but don’t mean that PPI use should be stopped. PPIs effectively treat gastrointestinal disorders, which carry their own risks.

Research Results: Four Findings

A study conducted among 244,679 patients in Denmark and presented at the 2016 American Heart Association’s Scientific Sessions sought to determine if strokes occurred while patients took one of four PPIs: omeprazole (Prilosec), pantoprazole (Protonix), lansopra-zole (Prevacid), and esomeprazole (Nexium).

The researchers found that:

  1. Overall stroke risk increased by 21 percent among patients who took a PPI.
  2. Those who took PPIs at the lowest doses had a slightly increased risk of stroke or no risk at all.
  3. At the highest doses, PPI stroke risk increased 30 percent with Prevacid and 94 percent with Protonix.
  4. There was no increased risk of stroke associated with acid-reducing medications (H2 blockers), which include famotidine (Pepcid) and ranitidine (Zantac).

Proton pump inhibitors come in tablet or capsule form and are supposed to be taken 30 minutes before the first meal of the day. They work by reducing the amount of stomach acid produced by glands in the lining of the stomach, and multiple studies have shown that they’re very effective for most patients.

Thomas Sehested, MD, the lead author and researcher at the Danish Heart Foundation, Copenhagen, commented on PPI effectiveness in light of the new evidence: “At one time, PPI’s were thought to be safe, without major side effects. This study further questions the cardiovascular safety of those drugs.”


What’s considered a low dose and what’s considered a high dose of proton pump inhibitors?

  • Prilosec
    Low dose: 20mg
    High dose: 40mg
  • Protonix
    Low dose: 20mg
    High dose: 40mg
  • Prevacid
    Low dose: 15mg
    High dose: 30mg
  • Nexium
    Low dose: 20mg
    High dose: 40mg

What to Do?

The effectiveness of PPIs now has to be weighed against health-threatening risks. Several lifestyle strategies can lessen or prevent those risks. To prevent a stroke, the Centers for Disease Control and Prevention suggests that you:

  • Eat plenty of fresh fruits and vegetables.
  • Maintain a healthy weight.
  • Get at least two hours and 30 minutes of physical activity per week.
  • Drink only in moderation.
  • Don’t smoke.

To lessen the probability of acid reflux, the National Institutes of Health recommend decreasing fatty foods, eating smaller but more frequent meals, and avoiding such foods as chocolate, coffee, tomato products, and spicy foods.

To reduce the risk of PPI-related ischemic stroke, the authors of the study make these suggestions:

  • Physicians who prescribe PPIs should carefully consider whether their use is warranted and, if so, for how long. Further, the drugs should be prescribed at the lowest possible dose for the shortest length of time.
  • Another option: Don’t take PPIs at all, but that decision should be made only after discussing the problem with your physician.

Originally published in 2017, this post is regularly updated.

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Diane Muhlfeld

Editor/writer Diane Muhlfeld joined Belvoir Media Group in 1996. Since 2002, she has focused on the company's growing health publishing division, which comprises 11 institution-affiliated newsletters and 24 annual Special … Read More

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