FDA Issues Statement on Entacapone, Cardiovascular Risk
Based on new safety review data, the FDA announced today that there is no clear evidence of an increased risk of heart attacks, stroke, or other cardiovascular events associated with the use of entacapone for the treatment of Parkinson's disease. As a result of these findings, the FDA states that changes to the labeling for both Comtan (entacapone) and Stalevo (entacapone, carbidopa, levodopa) are unnecessary.
In August 2010, the FDA issued an alert to healthcare professionals about a possible increased risk of cardiovascular events and death with the use of Stalevo. The issue was observed in a clinical trial called the Stalevo Reduction in Dyskinesia Evaluation in Parkinson's Disease (STRIDE-PD) and in a meta-analysis that combined cardiovascular-related findings from 15 studies comparing Stalevo to carbidopa/levodopa. Since carbidopa/levodopa have been used extensively and have not been associated with cardiovascular risk, the FDA was concerned that entacapone might have been responsible for the increased risk.
In order to get a better understanding of these findings, Novartis, the manufacturer of Stalevo, was asked to study the potential for cardiovascular risk with entacapone. Novartis's study assessed the potential for myocardial infarction (MI) associated with entacapone in patients aged 18 to 64 years with Parkinson's disease using data from an electronic commercial insurance database. The risk for MI that did not result in death was not significantly increased in patients treated with entacapone compared to the control group that received other Parkinson's disease drugs. No one in either group died from MI. This study had limitations, including that few patients had MI making it difficult to assess an association with the drug.
The second study assessed the risk of MI, stroke, or death in Medicare patients ≥65 years old with Parkinson's disease treated with entacapone compared to those receiving other Parkinson's disease drugs. The study results did not support an association between entacapone use and increased cardiovascular risks.
After examining the evidence from these two studies, the FDA concluded that entacapone was not associated with an increased risk of cardiovascular events and that the results observed in the original meta-analysis were driven by results from STRIDE-PD, which was not designed to assess cardiovascular risk. The FDA believes that the meta-analysis and STRIDE-PD results do not represent a true increase in risk and are likely chance findings.
Both Comtan and Stalevo are approved for the treatment of Parkinson's disease. Healthcare professionals are encouraged to continue to report adverse events or side effects related to these products.
For more information visit FDA.gov.