FDA: Long-Term Clopidogrel Neither Ups, Nor Cuts Risk of Death in CVD Patients
After an evaluation of several recent clinical trials, the FDA has announced that long-term clopidogrel use does not increase or decrease the risk of all-cause mortality in patients with, or at risk for, heart disease.
The Take Home
FDA concludes that clopidogrel treatment does not affect mortality in patients with or at risk for heart disease. Patients on clopidogrel should continue therapy as prescribed.
In meta-analyses of trials studying clopidogrel use of 12 months or longer—including the milestone DAPT Study—the FDA concluded that dual antiplatelet therapy of clopidogrel and aspirin “do not appear to change the overall risk of death” compared with therapy regimens of 6 months or less, the agency reported in a safety alert today.
Additionally, they found “no apparent increase in the risks of cancer-related deaths or cancer-related adverse events with long-term treatment.”
The DAPT Study was performed at the behest of the FDA to conclusively determine the optimal duration of dual antiplatelet therapy after DES implantation. It enrolled 25,682 patients within 72 hours of PCI at 452 sites in 11 countries, and randomized 9,961 DES patients at 12 months to continue to receive aspirin plus a thienopyridine (50.4%) or aspirin plus placebo (49.6%) from August 13, 2009 to July 1, 2011.
Rates of the primary efficacy endpoints of definite/probable stent thrombosis and MACCE (death, MI, or stroke) were lower in those who continued taking a thienopyridine than those who did not from 12-30 months. Longer DAPT was also associated with a lower cumulative incidence of MI, with 55% of this benefit driven by a lower incidence of MI not related to stent thrombosis (HR 0.59). The were similar rates of cardiac death, vascular death, and stroke between the study arms, yet all-cause death was higher in those who continued thienopyridine treatment.
But the question of how long to give antiplatelet therapy in these patients has remained open.
The FDA says it is “working with the manufacturers of clopidogrel to update the label to reflect the results of the mortality meta-analysis.” The agency recommends that patients continue “taking clopidogrel or other antiplatelet medicines because [stopping] may result in an increased risk of heart attacks and blood clots.”
Plavix (clopidogrel): Drug Safety Communication - Long-term Treatment Does Not Change Risk of Death [safety alert]. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm471531.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery. Published November 6, 2015. Accessed November 6, 2015.
- DAPT Study Shows Benefit of Long-Term Treatment After DES Implantation
- Despite New Findings, Optimal DAPT Duration Still Up in the Air
- DAPT Substudy: No Apparent Benefit of Long-term DAPT in BMS Patients