Update From the Medical Journals: May 2011 - What Your Doctor Is Reading - Harvard Commentaries

What's the latest news in the medical journals this month? Find out what your doctor is reading.

NSAID Pain Drugs are Hazardous if You Have Heart Disease
COPD Inhalers Can Make Urinating Difficult for Men
More News in Brief: Drug Slows Lethal Lung Disease, Early Start of HIV Treatment Prevents Spread, and Macular Degeneration Can Be Treated for Lower Cost

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen have risks. But they can be especially dangerous for people with coronary artery disease, a prior heart attack or heart failure.

A new study from Denmark found that deaths and heart attacks are more frequent among heart attack survivors or those with heart disease who used NSAID drugs, compared with people who did not use them. The study did not include aspirin, which is categorized as an NSAID. (Aspirin provides a clot-prevention benefit that makes it quite different from other NSAID medicines.) The study was published online May 9 by Circulation: Journal of the American Heart Association.

Researchers reviewed data collected from all Danish residents. They identified 83,697 people who had experienced a heart attack. The researchers kept track of who also took NSAIDs and for how long. By the end of the study, which lasted for years, more than one-third of the people in the study had either died or had a repeat heart attack. Forty-two percent of the people in the study received prescriptions for non-aspirin NSAIDs from their health care providers for various conditions.

The study was not a randomized study, so the results could be somewhat misleading. It is possible, for example, that NSAIDs were not the cause of all of the extra heart attacks. Instead, the pain conditions that were requiring NSAID use might have added a portion of the risk. Still, the results were alarming. Short-term use of NSAIDs was associated with a 45% increased risk of death or recurrent heart attack (roughly 3 NSAID users would have an event for every 2 non-NSAID users). There was a 55% increased risk if NSAIDs were used for 3 months or longer.

The study also compared the risks of NSAIDs to drugs called Cox-2 inhibitors. These are closely related to NSAIDs. Rofecoxib (Vioxx) was a Cox-2 inhibitor that was taken off the market because it caused heart attacks. The most high-risk NSAID they monitored in their study, diclofenac, seemed to be about equally dangerous to Vioxx. (In previous studies, Vioxx was linked to roughly twice the risk for heart attack.)

Why would NSAIDs have this risky effect? There are two reasons. Some people take aspirin to prevent blood clots. (Non-aspirin NSAIDs do not prevent clots very well.) To do this, aspirin molecules must attach to proteins on the surface of platelets. NSAIDs other than aspirin can attach to the same proteins. They prevent aspirin from "getting to its desk" to do its job.

Next, NSAIDs block a natural substance called "prostaglandin." This can lead to higher blood pressures, tighter arteries and mildly reduced kidney function when using NSAIDs.

Based on the results, the researchers recommend that people who have had a heart attack, heart failure or coronary artery disease avoid using NSAIDs (other than aspirin). They say keep NSAIDs to an "absolute minimum" — take the lowest dose possible for the shortest time possible, if at all. If you do overlap aspirin and non-aspirin NSAIDs, take the aspirin at least two hours before the other medication.

Chronic obstructive pulmonary disease (COPD) results from smoking. Inhalers can improve symptoms of wheezing and chest tightness. They force muscles in the airway to relax. But medicines that relax tone in one part of the body may have unintended consequences in other parts. A new study has shown that the most commonly used category of inhaler medicines in COPD put men at risk for being unable to urinate. This is called acute urinary retention.

Inhaled anticholinergic drugs include ipratropium (Atrovent) and tiotropium (Spiriva). Ipratropium is also one ingredient in the combination inhaler, Combivent. The study, which was published in the May 23 issue of the Archives of Internal Medicine, looked at these inhalers. For six years, researchers monitored the health records of 565,073 men and women with COPD. Doctors treated 9,432 men for acute urinary retention. The odds of needing treatment for urinary retention were 40% higher among men who had been treated with an anticholinergic inhaler for at least one month. The odds were 80% higher for men who used these inhalers and also had an enlarged prostate gland. (Urinary retention in women is much less common and it did not become a statistical concern in this study.)

Acute urinary retention is uncomfortable and is usually treated in an emergency room. Most people who develop acute urinary retention have to be sent home with a urinary catheter. The catheter is usually temporary, but taking medicines or removing prostate tissue surgically may be needed.

Based on this study, men who use ipratropium or another anticholinergic inhaler for COPD should use the minimum number of inhaler puffs that can control symptoms. If a man has an enlarged prostate, it is probably best to avoid these inhalers altogether. People who use these inhalers should report symptoms of incomplete bladder emptying, dribbling or leaking of urine, or difficulty getting urine to start its flow.

Drug Slows Lethal Lung Disease. A new drug may help a disease called idiopathic pulmonary fibrosis (IPF). There are few treatment options for IPF. Two studies published online by the journal Lancet on May 13 showed promising results for a drug called pirfenidone. IPF causes the lungs to become stiff from scar tissue (fibrosis). The disease is fatal because it steadily gets worse over time. Only 20% to 30% of people with IPF are alive 5 years after they are diagnosed. We don't know what triggers the scarring process of IPF. If we did, we could possibly stop the scarring by getting rid of the trigger. However, pirfenidone is an experimental drug that may slow or prevent scarring in IPF. This "anti-fibrotic" (anti-scarring) medicine prevents collagen from forming a scar. In the two Lancet studies, the drug slowed the rate of scarring. The most impressive of the studies randomly divided patients into two groups. The study showed changes in a measurement of breathing called forced vital capacity. A decline of 10% is a major milestone in this disease. About 20% of people who were treated with pirfenidone had this large decline after 72 weeks treatment, compared with 35% in a group that had a placebo treatment. The average drop in breathing ability was 8.4% in the pirfenidone group and 12.4% in the placebo group.

Early Start of HIV Treatment Prevents Spread. Antiviral medicines can prevent progression of HIV to its more advanced form, AIDS. But when is the right time to start these medicines? For years this question has been debated. Should HIV medicines be started when the immune system cell counts get low? Should they be started after the first significant infection? A large study has given us an excellent reason to start HIV drugs as soon as the condition is diagnosed. The study shows that treatment prevents HIV from spreading. Participants in the study included 1,763 couples. Most of the couples were heterosexual, not gay. In each couple, one person had HIV and one did not. The participants were from various countries in Africa, Asia, and South America, and the United States. All of the couples were advised to use condoms. Researchers randomly divided the HIV-infected partners into two groups. One group started on antiviral medicines right away. The other group waited until they had fewer than 250 CD4 cells (a type of immune system cell) or until they had an infection that resulted from having a weak immune system before starting antiviral medicine. The study began in 2005 and was supposed to continue for 10 years. However, the researchers stopped the study early because their findings midway through the study were so important. They saw that the healthy partners of HIV patients were 96% less likely to get HIV from their partner if their partner was on HIV treatment medicine. The U.S. National Institutes of Health and the research group it sponsors, the National Institute of Allergy and Infectious Diseases (NIAID), announced the study results May 12. More information about the study is available on the NIAID website.
Macular Degeneration Can Be Treated for Lower Cost. The most common cause of severe vision loss in people over the age of 65 is macular degeneration. This disease affects 1.4 million Americans. It is caused by abnormal growth of tiny blood vessels into or directly behind the retina, at the back of the eye. Five years ago an expensive drug became available to slow vision loss in macular degeneration. The drug, ranibizumab (Lucentis), is injected into the retina. Each injection costs about $2,000. Due to the high cost, a new study looked at different treatment options. Researchers tested less frequent injections and compared Lucentis to a less expensive drug. The New England Journal of Medicine published the study online April 28. The results of the study could reduce the cost of treating macular degeneration. Researchers divided 1,200 people with macular degeneration into four groups. One group got a monthly injection of Lucentis, which is the current treatment standard. Another group got Lucentis only when their eye disease was progressing. The other two groups got a different drug, bevacizumab (Avastin), either monthly or "as needed." Avastin costs $50 per injection. In the end, the different drugs seemed to be about equally effective, and less frequent injections of Lucentis seemed as helpful as monthly injections. One of the proteins responsible for forming new blood vessels is vascular endothelial growth factor (VEGF). Both Lucentis and Avastin are VEGF blockers. They help eyesight by preventing the growth of abnormal blood vessels behind the retina. Avastin is not currently approved by the U.S. Food and Drug Administration for treatment of macular degeneration, but it is already available on the market to treat some cancers.

Mary Pickett, M.D. is an associate professor at Oregon Health & Science University where she is a primary care doctor for adults. She supervises and educates residents in the field of Internal Medicine, for outpatient and hospital care. She is a Lecturer for Harvard Medical School and a Senior Medical Editor for Harvard Health Publications.