Proton pump inhibitors pose some very serious risks

Think twice about taking heartburn drugs

DRUG BUST by Alan Cassels

• Warning: this column is for people who are taking (or have been offered) heartburn drugs or are considering treatment for heartburn. In other words: most of us. If you develop heartburn or ulcers, there is a good chance you’ll be offered a prescription from the most effective – and possibly most inappropriately over-consumed – class of drugs on the planet: a proton pump inhibitors or PPIs.

PPIs include drugs like omeprazole (Losec® or Prilosec® in the US), lansoprazole (Prevacid®), rabeprazole (Pariet®), pantoprazole (Pantoloc®) or esomeprazole (Nexium®). They are given for a variety of things including dyspepsia (a catchall term for digestive problems such as stomach discomfort, gas, bloating, belching, appetite loss and nausea), peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD) and Zollinger-Ellison syndrome. Does stomach acid rising in your throat compel you to make a doctor’s visit? All I’m saying is there is a very good chance you’ll get a PPI faster than you can say “rebound acid hypersecretion.”

The popularity of these drugs is mind-blowingly huge and it’s not uncommon for people to wake up one day and realize they’ve been on the drug for a decade. Maybe you took your first one when you had a small developing ulcer or for an occasional bout of stomach acid that rises in your throat and burns like you’ve downed a red-hot poker. You feel bad because you have this nagging feeling you shouldn’t be taking the drug, but, at the same time, you’re strangely very happy because the little pill works really well in dowsing the flames.

There is one important thing you need to know from the approved product label for PPIs: they are approved for “short-term treatment” of GERD and duodenal and stomach ulcers that are “resistant” to antacids and H2-blockers. The operative phrase is “short term”, so what explains the fact there are upwards of 10 million scripts written every year for PPIs in Canada (about 100 million in the US), the third highest-selling class of drugs in North America?

For starters, PPIs are extremely effective at influencing the production of acid by the stomach. Remember, stomach acid is your friend, helping digest food and preventing infections, but too much of it in the wrong place can be uncomfortable. Up to 30 percent of Canadians will experience some kind of reflux in their lives and peptic ulcers affect roughly 10 percent of us. “Peptic ulcer” is an umbrella term for certain lesions – little pits or “craters” – in the mucous membranes or lining of the stomach and duodenum (top part of the small intestine), which can cause significant pain, bleeding, and, in rare cases, can erode all the way through the wall of the GI tract, leading to a perforated ulcer.

After we chew food, it makes its way down the esophagus and into our stomachs where the process of digestion begins: acid breaks down the food into its essential nutrients. GERD occurs when acid from the stomach ‘backs up’ into the esophagus, irritating it and, in the process, causing heartburn, nausea, burping or belching and an unpleasant taste in the mouth. A sphincter at the junction between the esophagus and the stomach is supposed to prevent your stomach contents from backing up into the esophagus, but it can malfunction for a variety of reasons. Generally, this happens after meals when the stomach is full and when lying down.

For eons, we thought ulcers were caused by stress and that the treatment was antacids, a bland diet or surgery. The ‘stress’ theory of ulcers soon came to be replaced by the ‘bacteria’ theory where a bacterium, Helicobacter pylori (H. pylori) was found to be one of the key causes of ulcers. In the early ‘70s, a revolutionary class of drugs – the H2 antagonists, including drugs like Tagamet or Zantac – were blockbusters in their own right, yet a mere shadow compared to the PPIs, which appeared on the scene in the mid ‘90s. Omeprazole (Losec® in Canada, Prilosec® in the US) was the first in a class of drugs that took the world of acid suppression drugs to a whole new level.

As I’ve said in the past, first comes the marketing, then comes the science, then comes the regret. I would say the PPIs are currently in the ‘regret’ stage. Soon after omeprazole hit the market in 1995, there were reports of adverse effects, including joint and muscle pain, muscle weakness and swelling. And cases of kidney inflammation were reported in some patients after the first few months of starting omeprazole.

In fact, during those early days, some doctors feared PPIs were too effective, because they allowed gluttony to run unchecked. They became a passport to stuffing one’s face without any consequences. In the early days, there were also concerns that prolonged use of PPIs could mask danger signs, such as cancer symptoms. In England, such concerns led to a 1998 warning from the Medical Research Council, which criticized doctors for putting all their indigestion patients on PPIs and failing to ‘step down’ to basic remedies. The Council warned patients would get put on a PPI and never actually have to deal with the lifestyle or other factors conspiring to cause the acid reflux in the first place.

Nearly 20 years later, what can we say? “Boy, were they ever right.” It seems that the strongest drugs to block acid, the high dose PPIs, turned out to be the most dangerous to use especially in the long term and in the elderly. But what sort of dangers do they pose?

The long-term consumption of PPIs has a range of potential dire consequences, which I’ve deemed the Four Risks of the PPI Apocalypse:

Rebound acid hypersecretion risk: wonder why so many people start the drug and can’t stop taking it? Dude, you can become dependent on PPIs in as little as four weeks on the stuff. This is a serious adverse effect that few people seem to be taking seriously. It is based on the fact that once you start feeling better, you stop taking the drug. The acid reflux comes back so strong it knocks you off your feet, therefore you go get another prescription. You have, sadly, become addicted to the stuff.

Fracture risks: taking PPIs for the long term in multiple daily doses increases risks of fractures of the hip, wrist or spine. When you’re tampering with the stomach flora, you’re also tinkering with the composition of your bones. Snap. Crackle. Pop.

Infection risks: the drugs are known to lead to an increased risk of infections, including pneumonia and C. difficile, which is particularly dire for elderly people who have spent time in a hospital. It could lead to them spending many more weeks in the hospital, or worse, dead.

Magnesium deficiency risk: it has taken a while, but information on the risk of severe magnesium deficiency has accumulated and is well known. If you are taking certain meds that alter your heart rhythm, low magnesium can make things a lot worse, including possibly life-threatening heart rhythm disruptions or arrhythmias.

Wait, there’s a fifth: a study out of Stanford University last summer found that “PPI use was associated with a roughly 20 percent increase in the rate of subsequent heart attack risk among all adult PPI users.” Those are pretty powerful words.

What to do when simple heartburn can lead you down a drug-filled path that could lead to a heart attack? Think alternatives.

There are tons of alternatives that can help relieve stomach acid and the best of these are lifestyle adjustments: losing some weight, eating more fibre, quitting smoking and drinking more water or green tea. Less restrictive clothing helps some people and some have found success with ginger, cabbage juice, digestive enzymes and probiotics.

In other words, you can search out alternatives, many of which might not be as powerful as a PPI, but there is something to be said for taking less powerful medicine; it is less likely to kill you or cause collateral damage that could make your life worse.

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Alan Cassels is a pharmaceutical policy researcher in Victoria and author of the just-published The Cochrane Collaboration: Medicine’s Best Kept Secret. Follow him on Twitter at @akecassels