Propoxyphene withdrawn due to risk for cardiac toxicity
The FDA has notified health care professionals that Xanodyne Pharmaceuticals has agreed to withdraw propoxyphene from the US market after new data have suggested that the drug may cause serious toxicity to the heart, even at therapeutic doses.
Propoxyphene, an opioid pain reliever for the treatment of mild to moderate pain and sold as Darvon, Darvocet and generics, was shown in a recent study to increase the risk for serious abnormal heart rhythms that may lead to death. The drug, which was first approved by the FDA in 1957, had received two requests to be removed from the market since 1978, but until now, the FDA had concluded that the benefits of propoxyphene for pain relief at recommended doses outweighed the safety risks.
“These new heart data significantly alter propoxyphene’s risk-benefit profile,” John Jenkins, MD, director, Office of New Drugs, in the FDA’s Center for Drug Evaluation and Research, said in a press release. “The drug’s effectiveness in reducing pain is no longer enough to outweigh the drug’s serious potential heart risks.”
According to the release, the FDA recommends that health care professionals stop prescribing and dispensing propoxyphene-containing products; contact and request patients currently taking propoxyphene-containing products to discontinue use of the drug; inform patients of the risks associated with propoxyphene; and discuss alternative pain-management strategies.
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Cardiac troponin T levels associated with HF, CV mortality in older patients
deFilippi CR. JAMA. 2010;doi:10.1001/jama.2010.1708.
Cardiac troponin T levels at baseline, as well as subsequent changes to levels, may predict patients at an increased risk for incident HF and CV mortality, data from a study published in the Journal of the American Medical Association involving a cohort of older patients revealed.
“Elderly individuals comprise the largest subgroup of patients hospitalized for HF, accounting for 80% of the more than 1.1 million US admissions per year,” the researchers said in their study. “Blood-based biomarkers, including CRP, natriuretic peptides and troponins, have been advocated as adjuncts to clinical risk factors to identify community-dwelling older patients at high risk for adverse CV outcomes, but studies examining the additive prognostic value of these markers have reported inconsistent results.”
This led the Maryland- and Texas-based researchers to conduct a longitudinal nationwide cohort study of 4,221 community-dwelling adults of at least 65 years of age without prior HF. They measured cardiac troponin T (cTnT) levels with a highly sensitive assay (Elecsys 2010, Roche Diagnostics) at baseline and repeated between 2 to 3 years later in 2,918 patients.
Levels of cTnT of at least 3 pg/mL were detected in 2,794 patients (66.2%). During a median follow-up of 11.8 years, researchers reported new-onset HF in 1,279 patients and 1,103 CV deaths. Highest cTnT concentrations (>12.94 pg/mL) when compared with undetectable concentrations produced an incident rate per 100 person-years of 6.4 (95% CI, 5.8-7.2; adjusted HR=2.48; 95% CI, 2.04-3.00) for HF and 4.8 (95% CI, 4.3-5.4; adjusted HR=2.91; 95% CI, 2.37-3.58) for CV death.
Further analysis revealed that in patients with initially detectable cTnT, a subsequent increase of more than 50% (n=393, 22%) was associated with a greater risk for HF (adjusted HR=1.61; 95% CI, 1.32-1.97) and CV death (adjusted HR=1.65; 95% CI, 1.35-2.03), whereas a decrease of more than 50% (n=247, 14%) was associated with a lower risk for HF (adjusted HR=0.73; 95% CI, 0.54-0.97) and CV death (adjusted HR=0.71; 95% CI, 0.52-0.97) vs. individuals with a 50% or less change.
Among the study’s limitations were the possibility that the increase in use of medications such as statins over the long follow-up time blunted the predictive value of cTnT, as well as the possibility of unmeasured and residual confounding to have influenced the results.
“Detectable cTnT levels as measured by a highly sensitive assay were present in the majority of community-dwelling older adults in this cohort, and higher concentrations — within a normal range established for a younger general population — reflect a greater burden of CV risk factors and imaging evidence of cardiac disease,” the researchers concluded. “Independent of these comorbidities, cTnT concentrations were associated with risk of new-onset HF and CV death.”
Furthermore, they said, longitudinal changes in cTnT concentrations were common in this cohort and correspond with a dynamic change in risk over time.