Low Dose Aspirin Increases the Risk of Upper Gastrointestinal Bleeding

Aspirin bottle. (iStockphoto)
Aspirin bottle. (iStockphoto)

Low-dose acetylsalicylic acid – also known as aspirin – (75 mg⁄day to 325 mg⁄day) is recommended for primary and secondary prevention of cardiovascular events, but has been linked to an increased risk of upper gastrointestinal bleeding (UGIB), according to a study published by Valkhoff and his colleagues (Can J Gastroenterol. 2013 Mar;27(3):159-67).

They analyzed several studies. All studies found low dose aspirin use to be associated with an increased risk of UGIB. The mean number of extra UGIB cases associated with low dose aspirin use was 1.2 per 1000 patients per year. Sounds like a small number when you think of the number of people who take aspirin all over the world. But the authors indicate use of low dose aspirin was associated with a 50 per cent increase in UGIB risk.

What about other anti-inflammatory drugs? Are they safe?

Commonly used traditional anti-inflammatory drugs like ibuprofen are also known as non-steroidal anti-inflammatory drugs (NSAID) are widely used for all kinds of pain. An editorial by Jacob Josh, Professor of Medicine, University of Ottawa, Ottawa, Ont. titled, “Anti-inflammatory drugs: What is safe?” (CMAJ August 29, 2006), says “Sixteen thousand deaths a year in the United States and 1900 a year in Canada were blamed on NSAID-induced gastric perforations, obstructions and bleeds. NSAID use was complicated also by numerous other side effects, including hypertension, heart failure and renal insufficiency.”

The risks are not limited to long-term use. Clinically significant adverse cardiovascular events are noted within the first 30 days of treatment.

Do you always have to take an NSAID if you are in pain and thus increase the risk of complications? Not really. You can try other modalities of pain relief by rest, application of ice and use of acetaminophen. Acetaminophen, up to 4 g/day, is as effective as an orally administered NSAID in about 40 per cent of patients with mild to moderate osteoarthritis.

Then there are occassions when pain cannot be relieved by what we call conservative measures. So we have to weigh our options. First, we should assess patient risk. There is an increased risk of gastric toxicity if:
-the patient is over 65,
-has had previous upper GI bleed,
-there is concurrent therapy with low-dose aspirin, corticosteroids or anticoagulants.

Under these conditions we should try prescribing a coxib (like Celebrex) or traditional NSAID with concurrent cytoprotection (to protect the stomach lining) with misoprostol or a proton pump inhibitor. If the patient has had a recent heart attack or episode of congestive heart failure, then he should not take NSAID or coxib.

Josh says, “In case of uncontrolled hypertension, we should not choose an NSAID or coxib until the blood pressure is well controlled. If the patient has controlled blood pressure that becomes elevated while taking an NSAID or coxib, even by 5 mm Hg systolic, adjust the antihypertensive medications or stop the anti-inflammatory, or both.” Monitor renal function as well.

Josh says there is nothing like a safe NSAID or coxib. In high-risk patients, we should avoid them. Concomitant use of low dose aspirin does not protect you from cardiac side-effects of NSAID or coxib. There is adequate data to suggest aspirin enhances the gastric toxicity of anti-inflammatory drugs as mentioned earlier.

If you are in pain, careful use of painkillers is very important. If you are taking aspirin as a prophylaxis against cardiac problems then weigh your risk factors and your options. If you are taking NSAID for chronic pain then you need to know your risks. Discuss risk vs. benefits of the medications you are taking with your doctor.

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Anti-inflammatory Agents (NSAID)

Wayne Gretzky seems to be suffering from arthritis. He is not alone. This disease afflicts 4 million Canadians. To stay comfortable, most arthritic patients are on anti-inflammatory agents.

These agents are steroids and/or nonsteroidal anti-inflammatory drugs (NSAID). Neither of them is completely safe.

Inflammation is body’s response to infection or injury. It is characterized by heat, redness, pain, swelling and, occasionally, loss of function.

If the inflammation is due to infection then antibiotic is required. To that one can add an anti-inflammatory agent to help reduce swelling and pain. If the inflammation is due to injury then an anti-inflammatory is enough. No antibiotic is required.

“Dr. B, I have arthritis and my doctor wants me to take an anti-inflammatory agent. I am scarred. My husband was on an anti-inflammatory and he almost bled to death. What are my chances of getting such a complication?”

This lady’s fears are shared by millions of people who are aware of the likely complications of anti-inflammatory agents. But there are millions more who are not aware of the risks.

It is estimated that 5 to 10 percent of patients will die from a bleeding ulcer as a result of NSAID use. The bleeding may start with no prior warning signs of an ulcer. This is true in 81 percent of cases, says a review article in the New England Journal of Medicine (NEJM).

Felix Hoffman, working at Bayer Industries, discovered the first NSAID (aspirin) 100 years ago. It was and is used for rheumatic diseases, menstrual pain, and fever. Since then numerous NSAIDs have been developed. These are one of the most widely used drugs – by prescription and off the counter.

It is estimated that 5 to 50 percent of patients will develop dyspepsia (upset stomach) due to NSAID use. But not necessarily develop an ulcer.

But the risk of developing an ulcer is high in patients who are advanced in age, have a previous history of ulcer, are on steroid (prednisone), are on blood thinner, have other medical problems, use more than one type of NSAID at a time, have bacterial infection of the stomach (H. Pylori), smoke, and use alcohol.

Most patients with osteoarthritis or rheumatoid arthritis have no choice but to take NSAID to stay comfortable. There are millions of people who take NSAID for other aches and pains. Therefore, it is important to make these medications safe.

Two strategies have been used to improve their safety, says the NEJM article. One is to prescribe concomitant medication to protect the lining of the stomach and duodenum and second is to develop safer anti-inflammatory agents.

Studies have shown that omeprazole (20 mg once a day), or misoprostol (200 mg three times a day) appear to be effective in preventing the recurrence of ulcers during continued use of NSAIDs.

Several newer NSAID agents are being studied (nabumetone, etodolac, meloxicam, celecoxib and rofecoxib). The authors of the review article say that the newer agents offer considerable promise in the treatment of inflammatory arthritis, but careful surveillance will be important to determine their ultimate benefit and safety profile.

In the meantime, vigilance on the part of physician and patient is required. Careful prescribing is important. Patients should follow directions properly. Especially, the individuals who consume regular off the counter anti-inflammatory agents.

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