PPIs and Heart Disease

Could you be taking a drug that increases your risk of dying from a heart attack?

It is only too common for cardiologists and GPs to prescribe drugs to reduce the risk of a heart attack.

But what if these same doctors were also giving you a drug which could increase your chance of having a heart attack and even doubled your chance of dying from a heart attack? Wouldn’t you want to know? And what if few doctors understood the dangers of these drugs?

The drugs I am talking about are called proton pump inhibitors (or PPIs) and they include omeprazole, lansoprazole, pantoprazole and esomeprazole. They reduce stomach acid. Doctors will tell you “they will protect your stomach if you are taking aspirin”. In fact they are far more dangerous than you or your doctor might realise. This is a time doctors don’t always know best. Let’s look at the evidence.

A publication in 2012 reviewed 23 studies of 222,311 people taking PPIs and found they had a 28% higher risk of cardiovascular events1. Another study in 2014 in Taiwan looked at 123,367 people with no history of heart disease who were taking PPIs and compared them with matched people who didn’t. Those taking PPIs were found to have a 58% higher risk of having a heart attack2.

A study in 2021 was even more damning. They looked at 4346 subjects who were initially free of heart disease who had taken PPIs for five years. This group had double the risk (2.02 X risk) of cardiovascular disease and over twice the risk (2.21 X risk) of heart failure3. The authors comment that this is another reason to be cautious of PPI overuse.

But it’s not just heart disease. A study of US veterans in 2016 gave a clear warning. These drugs increased all-cause mortality by 25%4. The risk of dying prematurely increased with the length of time taking the drug.

And PPIs also increase the risk of diabetes. A study of over 204,689 people found that regular PPI users had a 24% increase risk of diabetes. This risk increased with duration of use5. Oddly, people who were not overweight were more at risk. This is a pattern similar to that seen with statins. Diabetes is known to independently increase the risk of heart disease. A case control study from Germany also found PPI use was associated with a higher risk of type 2 diabetes6.

In 2015 researchers trawled through a massive 16 million documents from 2.9 million individuals. The results were worrying. Those on PPIs had a 16% increased risk of having a myocardial infarction7. But there was something far more disturbing. Those who did have a heart attack were twice as likely to die from it.

The bottom line is that these drugs are potentially lethal and increase your chance of developing almost every form of heart disease.

But why are people. taking PPIs more likely to die if they have a heart attack?  For a long time it has been known that PPIs deplete the body of magnesium. Magnesium is vital for muscles and especially for the heart. A study of 427 people admitted to critical care with heart attacks and unstable angina revealed a troubling finding. Those on PPIs had, on average lower magnesium levels and higher rates of arrhythmias and cardiac events8. The authors stated there was a statistically significant relationship between PPI use, magnesium levels and cardiac events with a strong correlation between all three.

Now it has been known that magnesium protects against heart disease and against irregular heart rhythms for a long time. For instance a review of seven major studies found that giving magnesium intravenously reduced death from heart attack by 55%9,10. Nothing else gives this degree of protection.

But magnesium does something else. It increases nitric oxide. This is a critical substance for the body because it dilates blood vessels. And it is known that PPIs reduce nitric oxide.

 If you have a heart attack and can’t produce nitric oxide you’re in big trouble. At a time like this being able to dilate your arteries can be the difference between life and death. But if you are taking a PPI this essential protective mechanism could well be blocked.

So why do doctors prescribe dangerous drugs like this to heart patients in the first place? The reason is because it is common policy to prescribe blood thinners like aspirin or clopidogrel to heart patients.

These do reduce the risk of further heart events. In the case of aspirin it is currently thought to reduce heart attacks by about 8%, and with clopidogrel, 10%. Unfortunately these drugs can cause stomach bleeding so they are often given PPIs, in addition, to protect the stomach. PPIs do protect the stomach but they endanger the heart and this danger outweighs any benefit that blood thinners might give.

“You are giving me aspirin to reduce my risk of a heart attack by 8% but you say you are also giving me a PPI and this is likely to increase my risk of a heart attack anywhere between 16 and 58% and doubles my risk of cardiovascular events and heart failure. Doctor, that doesn’t make sense, your figures don’t add up”.  And I understand that if  I should get a heart attack I would be twice as likely to die from it, that’s scary. Surely you’re not suggesting I should take a drug that could do that”.

Unfortunately, that’s exactly what many doctors, including many cardiologists are suggesting and it’s deadly advice.

  • 1) Int J Cardiol, 2012; 167(3): 965-74
  • 2) Int J Cardiol,2014;177(1): 292-7
  • 3) Mayo Clin Proc, 2021, 96(10): 2540-49
  • 4) BMJ Open, 2016; 7(6): e015735
  • 5) Gut, 2021;70(6): 1070-77
  • 6) Gut doi.10.1136/gutjnl.2021-326297
  • 7) Plos One, 2015 doi.org/10.1371/journal.pone.0124653
  • 8) Int J Gen Med,2013; 6:515-8
  • 9) Br Med J,1991; 303:1499-1503
  • 10) Drugs,1993; 46:347-359