“We already know that these drugs increase your risk of having a heart attack,” said Dr. Mike Knapton, associate medical director at the British Heart Foundation, in a statement. “However this large-scale study worryingly highlights just how quickly you become at risk of having a heart attack after starting NSAIDs.” Knapton was not involved in the research.
Knapton further added that people must be made aware of the risk and that alternative medication or treatment should be considered where appropriate. For example, physical therapy or yoga could be used to alleviate pain from an injury.
Association, not causation
The researchers stress that the findings are purely observational, as they used readily available data about certain populations. Not all potentially influential factors could be taken into account, they say.
Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, commented that a number of lifestyle factors, such as smoking and body mass index, are not available in the data about the study participants. “It leads to uncertainty,” he said.
Tobacco use, unhealthy diet, obesity, alcohol abuse and hypertension are just a few of many factors that can cause a heart attack.
“This is the largest study of its kind, but it is still observational data based on prescription or dispensing information, rather than whether people were actually taking their medication,” said Dr. Amitava Banerjee, senior clinical lecturer in clinical data science at UCL in the UK. “Although these data reflect real-world use of NSAIDs, it is impossible to control for all the factors which may lead to confounding or bias.”
This uncertainty combined with the overall observational nature of the findings means the cause of the increased risk shown in the analysis cannot be explained, nor can the drugs be directly stated as a cause of heart attacks.
Bally thinks a cause could be changes in blood pressure or effects on kidney function, as these areas are poorly studied. But she stresses that all five drugs studied have individual behaviors. “It will be hard to point to one factor,” she said.
Relative, not absolute risk
“The paper has good evidence that there is some risk of a heart attack for all NSAIDs and suggests that the risk starts immediately on starting them, but is only expressed in relative terms,” said Evans, who was not involved in the research. “There is no clear description of the absolute risk.”
The findings are based on the chances of a heart attack occurring in people taking these drugs, compared with those not taking them. If risk was already low in a person, a 20% to 50% increased risk is not that much cause for concern.
“The risks are relatively small, and for most people who are not at high risk of a heart attack, these findings have minimal implications,” Evans said.
It’s also possible that people taking these drugs are, on average, already at higher risk than people not taking the drugs, he said, commenting that the study did not account for these factors in their calculations. For example, the reason someone is prescribed an NSAID, such as for severe pain, may also be the reason they have a heart attack soon after. So while the study shows that risk of a heart attack increases as soon as a few days into taking NSAIDs, the links may not be as clear as suggested, Evans said.
“The most likely mechanisms for action of the drugs would be expected to show a low risk at the start and only have an effect on heart attacks after longer usage. That this wasn’t the case casts some doubt on the findings of an immediate increase in risk,” he said.
“All effective medicines have unwanted effects, and NSAIDs, although easily available, are not without some risks, but this study is no reason to induce anxiety in most users of these drugs,” he said.
But while waiting for more clarity on the true level of risk and its cause, experts still advise caution when prescribing or taking these painkillers.
“The increased risk of heart attack with NSAIDs, regardless of which one, means that both health professionals and the public should weigh up the harm and the benefit when prescribing these medications, especially for more than a day or two,” Banerjee said.
“Despite the over-the-counter availability of the traditional NSAIDs, this caution is still required. The mechanism of this increased risk of heart attack is not at all clear from existing studies.”