Various pieces of data mining have demonstrated that a number of very common drugs used to treat heartburn are actually linked to cardiovascular events. These drugs, known as proton pump inhibitors or PPIs, significantly increase the chances of suffering a heart attack. This risk is increased both for people who have a history of cardiovascular disease, and those who don’t.
Data has been assessed by researchers, who look at some 16 million clinical documents. These documents were collected on 2.9 million individual patients. Researchers looked specifically at pharmacovigilance information.
It was found that patients who took PPIs for gastro-esophageal reflux disease, were significantly more at risk of suffering a heart attack. The PPIs are designed to lower the production of gastric acid but it was also found that other types of heartburn therapy, most notably H2 blockers, did not lead to this increased risk. It was also noted that the risk of dying as a result of a cardiovascular event was twice as high compared to those who suffer a cardiac event that is not related to PPIs.
If the data that is now available through this data mining approach had been available earlier, it would have been possible for the risk to have been identified as soon as 2000. The drugs that are at particular scrutiny are:
- Lansoprazole
- Omeprazole
The lead researcher of the study is Nicholas Leeper, who is the Stanford University Medical Center assistant professor of surgery and medicine. He shared his findings in the journal PLOS ONE. The article was released on June 10, 2015.
There have been previous studies that showed that there is indeed a correlation between PPIs and developing major adverse cardiovascular events. However, this research only pointed to patients who also took clopidogrel, which is an antiplatelet drug. This drug is used to treat people who have developed blood clots and who have cardiovascular disease. The new study, however, did not look at clopidogrel in particular.
Each year, some 113 million prescriptions for PPIs are filled. In this country, there were around 21 million people who use at least one PPI on prescription in 2009 alone. This means that is the third bestselling type of drug in the country. It is worrying, therefore, that there is now a clear link between these drugs and developing an adverse cardiovascular event, even if no previous cardiovascular disease exists.
It must be noted, however, that this piece of research is the first of its kind and that there are no comparable studies that show the same results. However, due to the sheer scale of the investigation, the findings are certainly interesting and further investigation will be required. This has been agreed upon by various experts in the field. All experts now agree that the correlation is clearly there. However, they want to find out whether there is also a causal link and have therefore called for caution to stop people from jumping to conclusions much too quickly.
The current observation suggests that PPI usage does have a clear association with harm across the general population. This includes young people and people who do not take any type of antiplatelet agent. This means that PPIs may increase risks of cardiovascular events, but it is not clear how this happens. In the past, it was believed that the causality is in platelet aggrevation, but this has now been dismissed. It is suggested that dysregulation of the vascular nitric oxide synthase may be at the heart of the problem.
Two specific sources were used to gather the data for the study.
These were:
- Stanford Translational Research Integrated Database Environment or STRIDE, which is the hospital system used at Stanford; and
- Practice Fusion, which is an electronic health record (EHR) system, which is a web-based free to use for clinicians.
Clinical trials rarely capture all the different long term effects that can be caused by different drugs. However, thanks to the two above systems, it is possible to run virtual post-market clinical trials. This can be done by analyzing data from the real world, including millions of patient records, from which names have been removed. Clinicians enter data about their patients on the Practice Fusion application, in particular, and this can be used to perform further studies.
Currently, a huge amount of data is available that could help determine whether a certain type of medication will actually work better than others. It can also be used to determine whether a certain type of medication will have unexpected negative side effects. Electronic health records, therefore, have a huge long term value and power. These data sets have all been de-identified, so patient confidentiality is fully maintained. This is one of the greatest benefits of the digital world and information is growing rapidly.
Thanks to the data, it is now known that those who use PPIs have a 21% larger risk of having a heart attack than people who do not take this type of medication. The results from the study clearly show that the risk of suffering a heart attack is greatly increased and this is true for the general population. It should be noted, however, that some suggest that the risk increase is slightly lower, at 16%.
Many of the PPIs are available over the counter. In fact, they are some of the most commonly prescribed in the world. While some countries, such as the United Kingdom, only makes products like Lansoprazole available on prescription, they are still readily available and prescribed without many checks by physicians.
The FDA (the U.S. Food and Drug Administration) has taken note of the findings. They have reported that around one in 14 people in this country are prescribed PPIs. The drug is supposed to treat disorders such as Helicobacter pylori infection, gastro-esophageal reflux disease (GERD) and Barrett’s esophagus. There are various different brands of PPIs, including Prilosec, PrevAcid and Nexium. H2 blockers, which are not associated with the increased chance of heart attacks, include such brands as Tagamet and Zantac.
A large randomized trial will now be conducted. This will look at whether PPIs are particularly harmful to a broader patient population. Depending on the findings, there is a significant chance that various proton pump inhibitor lawsuits will be filed against manufacturers of these types of drugs.
