heartburn drugs may raise stroke risk

 

Proton pump inhibitors are a class of drugs commonly used to treat heartburn - pain in the chest or throat caused by the rising of stomach acid into the esophagus. But new research suggests this medication should be used with caution, after finding it could raise the risk of ischemic stroke.

A new study has linked the use of PPIs - drugs that treat heartburn - to greater risk of ischemic stroke.

In a study of almost 245,000 Danish adults, researchers found the risk of ischemic stroke was increased by a fifth with the use of proton pump inhibitors (PPIs).
PPIs work by reducing the amount of acid produced in the stomach, thereby reducing the "backing up" of stomach acid into the esophagus - a condition known as heartburn. Someone who has heartburn more than twice a week may have gastroesophageal reflux disease (GERD).
Lead study author Dr. Thomas Sehested, of the Danish Heart Foundation in Copenhagen, Denmark, recently presented his findings at the American Heart Association's Scientific Sessions 2016, held in New Orleans, LA.
Ischemic stroke occurs when the artery that supplies the brain with oxygen-rich blood becomes blocked, usually by a blood clot. Ischemic stroke is the most common form of stroke, accounting for around 85 percent of all strokes.
Dr. Sehested and colleagues note that previous studies have associated PPI use with vascular impairment, which led the scientists to investigate whether the drugs might raise the risk of ischemic stroke, "especially given their increasing use in the general population," notes Dr. Sehested.

Ischemic stroke risk 21 percent higher with PPI use

To reach their findings, the team analyzed data of 244,679 adults from Denmark - of an average age of 57 years - who underwent endoscopy to pinpoint the causes of their stomach pain or indigestion.
During an average of 6 years of follow-up, 9,489 patients experienced a first-time ischemic stroke.
The researchers assessed patients' use of one of four PPIs - omeprazole (Prilosec), pantoprazole (Protonix), lansoprazole (Prevacid), and esomeprazole (Nexium) - and looked at whether this was associated with ischemic stroke risk.
Overall, the team found that patients were at 21 percent greater risk of ischemic stroke when they were using PPIs, compared with when they were not using the drugs.
There was little or no greater risk of stroke with low doses of PPIs, the researchers report, and another group of medications used to treat heartburn - called H2 blockers - were not linked to increased stroke risk.
Looking at stroke risk among the highest doses of each of the four PPIs, the researchers found pantoprazole fared worst, increasing the risk of ischemic stroke by 94 percent.

Study 'questions the cardiovascular safety of PPIs'

The researchers accounted for a number of possible confounding factors, including age, gender, high blood pressure, atrial fibrillation, and use of medications that have been linked to poorer cardiovascular health.
Because the study is purely observational, the researchers are unable to prove cause and effect between PPI use and increased stroke risk. Still, they believe the results suggest patients should be cautious about using the drugs, many of which are now available over the counter.

"At one time, PPIs were thought to be safe, without major side effects. This study further questions the cardiovascular safety of these drugs."

Dr. Thomas Sehested

Dr. Sehested notes that doctors should also apply caution when deciding whether to prescribe PPIs to patients and for how long. "We know that from prior studies that a lot of individuals are using PPIs for a much longer time than indicated, which is especially true for elderly patients," he adds.
The team concludes that a randomized, controlled trial of the association between PPI use and the risk of cardiovascular disease is needed.
Read how younger pregnant women may be at greater stroke risk than older expectant mothers.

Written by Honor Whiteman

 A type of heartburn medication called proton pump inhibitors may be linked to long-term kidney damage, a new study suggests.

Prilosec, Nexium and Prevacid belong to this class of drugs, which treat heartburn and acid reflux by lowering the amount of acid produced by the stomach.

People who use proton pump inhibitors (PPIs) have a 20 percent to 50 percent higher risk of chronic kidney disease compared with nonusers, said lead author Dr. Morgan Grams, an assistant professor of epidemiology at Johns Hopkins University in Baltimore.

The study was published Jan. 11 in JAMA Internal Medicine.

The study doesn't establish a direct cause-and-effect relationship between the drugs and chronic kidney disease. However, Grams said, "We found there was an increasing risk associated with an increasing dose. That suggests that perhaps this observed effect is real."

Proton pump inhibitors were used by more than 15 million Americans in 2013, according to background notes.

But as many as 70 percent of these prescriptions have been handed out inappropriately, and 25 percent of long-term users could stop taking the medication without suffering increased heartburn or acid reflux, the study authors said.

Use of the prescription heartburn drugs already has been linked to short-term kidney problems such as acute kidney injury and an inflammatory kidney disease called acute interstitial nephritis, Grams said.

Newer studies now show a link between the drugs and chronic kidney disease, in which the kidneys lose their ability to filter blood effectively.

Over time, chronic kidney disease can lead to kidney failure, forcing someone to undergo regular dialysis and possibly a kidney transplant, according to the U.S. National Institutes of Health.

In this new study, researchers used data on self-reported proton pump inhibitors use among more than 10,000 people taking part in a national study on hardening of the arteries. The researchers also evaluated data on outpatient PPI prescriptions among nearly 250,000 patients of a health care system in Pennsylvania.

From the start, PPI users in both groups were more likely to have health problems, such as obesity, high blood pressure and heart problems, the study noted.

In both groups, researchers associated use of the drugs with an increased risk of chronic kidney disease over 10 years.

The researchers also compared people using the drugs once a day with people who used them twice a day. They found twice-daily use was associated with a 46 percent increased risk of chronic kidney disease, versus a 15 percent increased risk in those taking one daily dose.

No one is sure how the drugs might damage the kidneys, but a couple of leading theories exist, Grams said. The medications can cause magnesium levels to decline in the body, and a lack of this important mineral could damage the kidneys. The kidneys also might become damaged over time if patients suffer repeated bouts of acute kidney inflammation due to proton pump inhibitors.

Gastroenterologists already are cautious regarding the use of the drugs, because they've been tied to other health problems such as bone fractures and infections of C. difficile and pneumonia, said Dr. Arun Swaminath, director of the inflammatory bowel disease program at Lenox Hill Hospital in New York City.

"We have started to limit the time you have to be on it, and limit the amount you take," Swaminath said.

Because the new study isn't a clinical trial, it doesn't prove that PPI use causes chronic kidney disease, said Dr. Kenneth DeVault, president of the American College of Gastroenterology and chair of medicine at Mayo Clinic in Jacksonville, Fla.

"These types of studies, these big data studies, can sometimes suggest a signal that something's going on, but I don't know if they prove it," DeVault said.

It's possible that the drug users suffer chronic kidney disease more often because they have overall poorer health, he said.

Grams said the study authors tried to address that concern by comparing PPI users to people using another heartburn medication called H2 blockers. Both patient groups tended to be equally unhealthy, but PPI users had a 39 percent higher risk of chronic kidney disease, the researchers said.

While this study shouldn't lead anyone to knee-jerk stop using proton pump inhibitors, people who use them regularly should talk with their doctor about whether they really need them, Grams and DeVault said.

"If you don't need these medicines, you shouldn't take them," DeVault said. "That said, there are reflux patients with heartburn who really need the PPIs to help them with their symptoms."

Doctors also might opt to prescribe an H2 blocker like Pepcid, Tagamet or Zantac. "To me, this is a cheaper, safer alternative that might work as well with some patients," Swaminath said.