Common Painkillers Increase the Risk of Heart Attacks
Introduction
A recent meta-analysis study in the British Medical Journal [1] suggests that using NSAIDs (a commonly prescribed type of painkiller) increases the risk of acute myocardial infarction (heart attack).
This study is open access and you can read (or download) it here.
What is new here?
Not much to be honest. It was already known that NSAIDs increase the risk of MI (heart attacks).
There was some debate as to whether there were differences in risk between the different classes of NSAID (COX 1 vs COX2 inhibitors) and different individual drugs.
This study suggests that all these drugs increase risk to an almost identical degree (except for Celecoxib which seems to have a lower OR). I have summarised the main results in the table below:
Table 1 Summary of Results
| NSAID DRUG | MI Risk (Odds Ratio) |
|---|---|
| Celecoxib | 1.24 |
| Rofecoxib* | 1.58 |
| Ibuprofen | 1.48 |
| Diclofenac | 1.50 |
| Naproxen | 1.53 |
Risk increases almost immediately
The increase in risk seems to be almost immediate and peaks at one month (except for diclofenac).
The risk also appears to be dose dependent so the higher the dose of the drug being taken, the greater the increased risk of having a heart attack.
Rofecoxib not as bad for heart attacks as previously thought?
One point of note is that Rofecoxib (Vioxx) was withdrawn by the manufacturer over a decade ago.
This was following concerns over its risk of increasing heart attacks and stroke.
It is interesting that this study does not show a huge difference between Rofecoxib and the other NSAIDs.
Confounding Factors
Particular care was taken to examine and control for confounding factors - I won't cover it here as there is a lot of information but you can read about on page 4-5 of the study.
Confounding factors are things such as age, diabetes status and so forth which could change the risk of a heart attack independently from the NSAID drugs which are being studied.
They are one of the biggest problems in medical research and if you read my blog you will often see me talking about them. Although we can take measures to reduce their effect there is no way to completely eliminate them.
Problems
Bayesian Statistics
This study has a peculiarity that makes it more difficult to interpret.
It uses a different type of meta-analysis from that which is conventionally used, it is called Bayesian meta-analysis and you can read more about here.
According to the Cochrane Handbook[2]:
"Bayesian statistics is an approach to statistics based on a different philosophy from that which underlies significance tests and confidence intervals [classical analysis]."
I won't even pretend to fully understand the statistical intricacies of how this differs from the standard statistical models.
The Cochrane Handbook link I have provided above has a summary but as they state:
Statistical expertise is strongly recommended for review authors wishing to carry out Bayesian analyses.
I'm afraid I don't have that kind of statistical expertise and this presents a problem in that I can't render the same kind of analysis which I could normally.
If you are experienced with this type of analysis I would love to hear your thoughts.
Other Issues
There are some other problems here too. This study incorporated results from 4 studies for analysis - a total of 8 studies actually met the inclusion criteria however:
"four ultimately had to be excluded because of ethico-legal restrictions placed by health authorities on transfer of IPD to third parties."
This creates a potential source of bias. A further issue is that it reduces the statistical validity of the data by reducing the potential sample size.
A smaller sample consisting of fewer studies means that the effect of any oddities or inconsistencies would be greater.
The total cohort was still quite large at 446 763 (61 460 heart attacks) so I don't want to overplay this.
Another interesting point is mentioned by the authors towards the end of the paper:
In particular, we could not study whether the effect of past doses of NSAIDs per- sisted and affected current risk nor could we determine the precise onset of any associated increased risk or the exact duration of any persistence of risk after stopping an NSAID.
In particular, for diclofenac, the risk of myocardial infarction with treatment for more than 30 days (blue and lavender lines in g 2 and table 3 ) is higher than with treatment for 8-30 days (brown and red lines in g 2 ), which hints at cumulative effects for this drug.
So although it appears that the increase in risk happens quite rapidly it is not possible to quantify exactly how long it takes to occur - for example does just a single dose increase your risk?
Also how long does it take for the risk to return to normal, indeed, does it return to normal?
The findings with diclofenac suggest that the effects might persist for a longer period and more specific studies would be needed to examine these issues.
What If I am Taking these Medications?
I would not suggest taking any drastic action right away. It has already been known that this link exists so there is no reason to panic.
If you have a lot of risk factors for heart disease (e.g. previous angina or coronary artery disease, high blood pressure, diabetes, strong family history etc.) or are really concerned - discuss this issue with your doctor.
It may be possible to minimise your dosage or consider other options to reduce the potential risk.
Whilst this study would suggest reducing or stopping NSAIDs would be a good thing - we must always take into consideration the balance of benefit vs risk and the potential for unforeseen consequences.
For example, if you have chronic pain which severely limits your activity then stopping your NSAIDs may paradoxically not reduce your risk of a heart attack if it results in you becoming more sedentary and/gaining more weight.
Chronic pain itself may be a risk factor for increased cardiovascular risk (at least indirectly).
For example I have seen a number of studies that link chronic pain with depression, and depression is a significant risk factor for cardiovascular disease.
So just to re-iterate, don't change anything without discussing it with your doctor first.
Quick note about this post
I have noticed that as my posts get longer people tend to read them less and this is understandable as most people are short of time.
I have therefore made this post more brief and used a slightly different way of breaking down the information. I won't always be able to do it but will try to make things more brief when I can.
It is a difficult balance to achieve though, and I hope I have got it right.
Please let me know what you think - is it too simple, not simple enough or about right?
Thank you for reading
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References
Bally, Michèle, Nandini Dendukuri, Benjamin Rich, Lyne Nadeau, Arja Helin-Salmivaara, Edeltraut Garbe, and James M. Brophy. 2017. “Risk of Acute Myocardial Infarction with NSAIDs in Real World Use: Bayesian Meta-Analysis of Individual Patient Data.” BMJ 357 (May): j1909.
Higgins JPT, Green S., ed. 2011. “Cochrane Handbook for Systematic Reviews of Interventions: 16.8.1 Bayesian Methods.” The Cochrane Collaboration. http://handbook.cochrane.org/chapter_16/16_8_1_bayesian_methods.htm.
Excellent post dear friend @thecryptofiend, it is never too long or short a post when the news is interesting, congratulations on this current topic that you have approached, really amazing, thank you very much for sharing all this information
Thanks!
I think this post is about right.
You transmit the message core and if anyone want more information can search in the sources.
Thanks for share it.
Cool thanks for letting me know!
I appreciate posts citing peer-reviewed meta studies, thanks for that!
You are welcome.
If one were to take Ibuprofen every day, drink a few Diet Cokes, smoke a pack of cigarettes, and eat a pack of Gummy Bears, I wonder how long it would take for the Grim Reaper to show up?
If it was me it would probably happen within a week. If it was some of the more evil members of my family they would probably live to be 150 years old!
The pro wrestling business is a testament to this. A lot of people think it's general drug and alcohol abuse that's killed a lot of wrestlers at or before their 40s, but in actuality it's painkiller abuse.
But I don't think those wrestlers use NSAIDs. They are mostly prescribed opiate painkillers which are totally different drugs, much less toxic than NSAIDs to the human body. But the downside is they give euphoria and highly addictive. So a lot of people abuse then and sometimes it is possoble to overdose when mixed with alcohol.
Good point. But at the same time, wrestlers are known to not always use prescription drugs. Or that's how it used to be, the business has actually cleaned itself up by a considerable amount in the past 10 or so years.
Yes I know a lot of them use painkillers quite heavily.
Thank you for sharing about the importance of health, especially heart. Because many of us now many do not care, do not we know that prevention is better than cure
You're welcome.
I wrote about this study a few months ago.
It was published 3 days ago - did you get an advance copy?
time-travel is real, I knew it!
:)
No no advance copy. I see now this article is a meta-analysis. I wrote about one of the studies they clearly analyzed. The results are slightly different, ie they state that Naproxen is worse then Ibuprofen which was not previously reported.
I am not sure yet how I feel about any of these studies.
Yes I think I remember it. That is the problem with research it is never quite finished. I think what we really need is something that quantifies the risk in relation to other factors and like I mention at the end chronic pain may itself up your risk of cardiovascular diseases so we need more information before reading too much into this.
I seem to remember that depression can increase cardiovascular outcomes like MI by a factor of 2-4 times (depending on the exact outcome) and that dwarfs the magnitude of the risk here quite significantly.
This is a good point.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2771193/
2.6 fold increase in congestive heart failure occurrence for depression. Would have to look for more to find MI. But yeah seems like many confounding factors.
Thanks for finding that link - yes it is quite striking! Another interesting point is that NSAIDs may be able to treat depression - it is still controversial but I have seen a number of studies that suggest this so would be interesting to examine this interaction.
I've never read anything about Cox inhibition and depression before. Might have to look into that a bit. Seems interesting.
The hypothesis is that it is based on the idea of depression being caused by a chronic inflammatory process. I seem to remember something in relation to paracetamol (acetaminophen) and depression too and obviously the mechanisms would be similar.
This is valuable information. I studied Biomedical Science for Public Health at TAMU. This is an objective, well balanced interpretation of the results of the research. Thanks for posting.
Thanks that is very kind.
Superb post. Great information. Thanks for sharing
Thank you:)
Well, I do my best to stay away from pills.
Good policy.