Safety Concerns About Pain Medication Naproxen Might Be ‘Overblown,’ Lead Study Author Says
"Fevered reaction" to the preliminary results of a study released this week that indicated the pain medication naproxen might increase patient risk for heart attack and stroke by 50% "may be overblown," and safety risks of the medication remain "unclear," according to the lead author of the study and other medical experts, the Wall Street Journal reports (Regalado/Winslow, Wall Street Journal, 12/23).
FDA on Monday announced that the National Institute on Aging study had found a 50% higher risk for cardiovascular events among participants who took naproxen compared with those who took a placebo. Lead study author John Breitner of the University of Washington and the Veterans Affairs Puget Sound Health Care System said at the time that although researchers must conduct additional analysis to determine whether the higher risk is statistically significant, the initial evidence was "enough to cause some concerns."
The study -- which began in 2001 and involved about 2,400 healthy adults ages 70 and older who had family histories of Alzheimer's disease -- sought to determine whether naproxen, sold over the counter by Bayer as Aleve, or Celebrex, a COX-2 inhibitor manufactured by Pfizer, could prevent the disease. Participants received either the recommended OTC dose of naproxen -- 220 milligrams twice daily -- 200 milligrams of Celebrex twice daily or a placebo. Seventy participants experienced heart attacks or strokes during the study, but researchers have not released data on which medications those participants received.
Researchers said that 23 participants died during the study, with no significant difference in death rates among those who received naproxen, Celebrex or a placebo. Breitner said that researchers decided to suspend the study after Pfizer on Friday announced that Celebrex might increase patient risk for heart attack and stroke. The Celebrex announcement prompted many participants to threaten to leave the study.
Breitner said that although the "safety data for some time has been giving a weak signal of possible increased risk of cardiovascular and cerebrovascular problems with naproxen," researchers did not end the study for that reason. NIH and the researchers said that they decided to suspend the study as a precautionary measure (California Healthline, 12/21).
Breitner on Wednesday said that the evidence of naproxen's side effects found in the study was "not really" statistically significant. According to Breitner, researchers had to combine several side effects and manipulate the data to detect an increased cardiovascular risk among study participants who received naproxen, and only for nonfatal side effects.
Breitner said that only two or three study participants who received naproxen or the placebo died from heart attack and none died from stroke, adding, "So there is no inference you can draw." Breitner said that the Celebrex announcement led to a "tremendous degree of public panic" and forced researchers to end the study.
Susan Molchan, director of the Alzheimer's disease clinical trials program at NIG, said that many study participants ended treatment over concerns that they had received Celebrex. Molchan said that researchers suspended the study because of "a series of unfortunate events," adding, "We tolerate so little risk that we ended up for nonscientific reasons stopping the trial."
NIH Director Elias Zerhouni said that safety risk for study participants was low because they were healthy.
Christopher Cannon, a cardiologist at Brigham and Women's Hospital and Harvard Medical School, said that FDA should have presented the preliminary results of the study in a "more rigorous fashion" to avoid "adding to the confusion and ... creating some harm."
Researchers said that they will attempt to "salvage what data they can from the trial," which has cost NIH about $26 million, the Journal reports.
Officials for the European Medicines Agency on Wednesday said that they will accelerate a safety review of pain medications as a result of the Celebrex announcement. EMEA officials cited data that indicated Celebrex might lead to "an increased risk of serious cardiovascular events."
In October, EMEA began a safety review of COX-2 inhibitors and planned to hold a hearing on the medications in February. EMEA officials on Wednesday said that they have decided to move the hearing to January.
In addition, EMEA officials said that they have asked pharmaceutical companies that manufacture COX-2 inhibitors to submit by early next year all results of their human clinical trials on the medications to determine whether additional safety studies are required (Regalado/Winslow, Wall Street Journal, 12/23).
In related news, the study that prompted Merck in late September to withdraw from the market the COX-2 inhibitor Vioxx has indicated the medication might prevent recurrence of colon polyps, which can develop into colorectal cancer, but the potential benefit "appears to fall well short of a turnabout for Vioxx," according to a physician who led the study, the Journal reports.
Robert Bresalier, a physician at the MD Anderson Cancer Center, said that although the study indicates Vioxx can prevent recurrence of colon polyps more effectively than other medications, such as aspirin and calcium, the potential benefit would not supersede the safety risks. "At this point, I wouldn't suggest that this is a viable agent," Bresalier said.
Merck spokesperson Joan Wainwright would not comment on the study results, which researchers will present in May at a medical conference, but she said that the company has "no plans to put the drug back on the market" (Regalado, Wall Street Journal, 12/23).
Several newspapers have published features related to recent safety concerns about pain medications. Headlines appear below.
Baltimore Sun: "Lining Up Suits Against Painkillers" (Vozzella/Penn, Baltimore Sun, 12/23).
Philadelphia Inquirer: "FDA's Approval Policy Pits Speed Against Safety" (Pugh/Borenstein, Philadelphia Inquirer, 12/23).
Seattle Times: "Painkiller Users Shouldn't Panic, Experts Say" (King/Sommerfeld, Seattle Times, 12/22).
USA Today: "Tough Choice: Pain or Risk?" (Szabo, USA Today, 12/23).
Wall Street Journal: "Drug Risk Can Pale Next to Pain -- Prescriptions for Celebrex Sink, but Many Doctors Want the Choice" (Burton/Helliker, Wall Street Journal, 12/23).
- Washington Post: "Warnings About Medications' Risks Add Worry to Pain" (Vedantam, Washington Post, 12/23).
NPR's "Morning Edition" on Thursday reported on the recent connections between four popular pain medications and increased cardiac risks and the lack of FDA authority to require additional safety trials. The segment includes comments from Richard Evans, analyst at Sanford Bernstein; McKinnell; and Eric Topol, a cardiologist at the Cleveland Clinic (Prakash, "Morning Edition," NPR, 12/23). The complete segment is available online in RealPlayer.This is part of the California Healthline Daily Edition, a summary of health policy coverage from major news organizations. Sign up for an email subscription.