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Deaths from Stroke Rise With Use of Certain Painkillers
Posted in CPR News
Monday February 9, 2015


I suspect in almost every household in America people have non-steroidal, anti-inflammmatory drugs (NSAIDs), sometimes used as painkillers. All NSAIDs have side effects, and new research published in the journal Neurology shows that increased risk of death from stroke comes along with certain of these drugs.

Many of these drugs are sold over the counter and can be purchased in pharmacies, grocery stores, and gas stations. The most common names are ibuprofen and naproxen, but when you take into account prescription formulations there are over 20 different types. They are also sold in combination with other medications used for sleep aids, migraine headaches, and cold and flu medications.

How Do NSAIDs Work?
NSAIDs block an enzyme in our body that is used to create inflammation called cyclooxygenase. When this enzyme is partially blocked, the body creates less inflammation. Hopefully, the body also experiences less pain.

The ways various NSAIDs block cyclooxygenase are different. Some block both cyclooxygenase enzymes (COX-1 and COX-2). These are called non-selective NSAIDs. Others only block COX-2, and are called selective. COX-1 is found throughout the body including the stomach, blood vessels, and part of the blood (platelets). COX-2 is more concentrated in areas of inflammation or injury. So there are potential advantages in just blocking COX-2 to reduce inflammation and hopefully experience fewer side effects.

An example of a COX-2 inhibitor is celecoxib (Celebrex). This is sometimes given to people who experience stomach pain with other NSAIDs or have a history of prior stomach bleeding or stomach ulcers.

NSAIDs side effects can include:
  • Stomach pain and irritation
  • Kidney injury particularly when a person is dehydrated
  • Liver injury
  • People who have a history of a heart condition, like coronary artery or multiple risk factors for coronary artery disease, may be at higher risk of a heart attack with NSAIDs use. In people with heart disease, chronic use of NSAIDs may increase risk of heart failure or worsening of heart failure. In people with coronary artery disease the risk of problems may be slightly less with naproxen, but there remains a slightly higher risk compared to people who don't use NSAIDs.

New NSAIDs Risks Discovered
Some of the risk from NSAIDs use is because the drugs alter platelet function in the blood. Platelets are little particles in our blood that lump together to form a clot. If these platelets become stimulated they can form small clots in people at risk and this can lead to a heart attack. They can also become dysfunctional and increase bleeding risk. For this reason, NSAIDs are often held back before you have a surgery. The mechanisms of why they can make you at higher risk to experience both clots and bleeds are complex and vary from person to person.

When a small clot or bleed occurs in the brain it is called a stroke. Depending on the size and location of the injury, symptoms can range from mild, to disabling, or even death. Given the effect of NSAIDs on clotting and bleeding it is reasonable to be concerned that these agents increase stroke risk. In fact, previous studies have shown the use of some NSAIDS can nearly double the risk of stroke. It is also possible since these agents alter platelet function they may increase the extent of the stroke and as such increase disability and death risk.

New Evidence of Stroke Risk With NSAID Use
A new study helped to determine if chronic NSAIDs use would increase stroke-related deaths. The authors particularly wanted to understand if COX-2 inhibitor NSAIDs might have a lower risk. The study was a from Denmark and examined 100,043 patients over eight years.

Here is a summary of their findings:
  • People who used COX-2 NSAIDs chronically were 19 percent more likely to die from a stroke related to a clot, compared to those who did not use the drugs.
  • Stroke-related deaths did not increase for patients using the nonselective type NSAIDs long-term, compared to nonusers.
  • New use of nonselective NSAIDs also did not increase risk of death from stroke within 30 days. However, new use of COX-2 NSAIDs did increase risk of death from stroke by 20 percent in the first 30 days of use.
  • Of the agents available in the United States, new use of celecoxib (Celebrex) was associated with a 12 percent increase in deaths from stroke within the first 30 days of use.
  • None of the NSAIDs increased risk of death from the type of stroke that is related to bleeding in the brain.

When to Consider Other Options for Pain
The increased mortality after a stroke in patients using a COX-2 inhibitor NSAID was seen across all agents. This suggests that there is a drug-class effect. Fortunately, with newer agents, in particular the one available in the United States, the risk is less. Since the risk is primarily driven in patients that recently started these agents, care and consideration must be taken when considering using these agents for long-term pain treatment.

If you are at risk of stroke, or have experienced a prior stroke, consider other pain control options that do not have the increased risk of stroke death, such as acetaminophen.

For those of you who have been using a nonselective NSAID or a COX-2 inhibitor NSAID long-term, these results do not show an increased risk of death related to stroke or increased risk of death related to bleeding in the brain. I believe that is good news. However, there remains a generally recognized higher risk of heart attack, heart failure, and stroke so if alternative agents will work for you consider their use. These discussions regarding long-term use and alternative agents should be made with your physician.

With all medications there is a trade-off between risks and benefits. In my experience the NSAIDs drug class is by far the best medication to decrease pain from arthritis. In some people, if NSAIDs are stopped they become largely crippled and then suffer the ill effects of immobility. To them, the risks involved with using NSAIDs are far lower than the obtainable benefits derived from remaining active and mobile. In some patients, regularly dosed acetaminophen works to reduce pain enough to maintain their quality of life. In these patients the risk of chronic exposure to NSAIDs is greater than the benefit, since an alternative agent can be used.

This new study helps us further understand the risks associated with these drugs and will help you and your physician make decisions regarding how to best treat your pain long-term.

 
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