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DOI: 10.1055/s-0037-1615253
Assessing Cancer Signal during Oral Antiplatelet Therapy in the Food and Drug Administration Adverse Event Reporting System: Mission Impossible
Publikationsverlauf
16. August 2017
14. November 2017
Publikationsdatum:
29. Januar 2018 (online)
Abstract
Whether aggressive prolonged dual antiplatelet therapy (DAPT) promotes solid cancer risks remains a critical unsolved issue. Since the evidence from randomized trials, affiliated U.S. Food and Drug Administration (FDA) reviews, meta-analyses, and national registries is mixed, the search is ongoing. The FDA Adverse Event Reporting System (FAERS) is a global passive surveillance repository requiring mandatory updates for serious events. We assessed the frequencies of co-reporting any cancers with oral antiplatelet agent (OAA) strategies in FAERS. We examined the entire FAERS database (n = 8,604,889) with regard to monotherapy or DAPT with OAA, suspected causative role, and co-reporting any cancers (n = 433,111). We extracted cancer cases during monotherapy with aspirin (20,984 out of 462,371 or 4.54%), clopidogrel (2,797 out of 62,791 or 4.45%), prasugrel (119 out of 4,364 or 2.73%), and ticagrelor (144 out of 8.268 or 1.71%). DAPT with clopidogrel reported (2,453 out of 58,101, or 4.22%); prasugrel (162 out of 4,036, or 4.01%); and ticagrelor (195 out of 5,302 or 3.68%) cancer reports all on top of aspirin. We conclude that FAERS is currently unreliable for adequate assessment of cancer risks during DAPT. The retrieved evidence appears random and sporadic, while associated cancers are heavily underreported or/and missed. Without stricter rules, better surveillance, and enforcements, oncology outcome research options in FAERS are challenging.
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References
- 1 Serebruany VL. Platelet inhibition with prasugrel and increased cancer risks: potential causes and implications. Am J Med 2009; 122 (05) 407-408
- 2 Mauri L, Kereiakes DJ, Yeh RW. , et al; DAPT Study Investigators. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med 2014; 371 (23) 2155-2166
- 3 FDA Drug Safety Communication. FDA reviews long-term antiplatelet therapy as preliminary trial data shows benefits but a higher risk of non-cardiovascular death. Available at: http://www.fda.gov/drugs/drugsafety/ucm423079.htm . Accessed July 27, 2017
- 4 Food and Drug Administration. Clinical review on cancer risk. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206316Orig1Orig2s000MedR.pdf . Accessed July 3, 2017
- 5 Food and Drug Administration. Briefing document, February 3, 2009, meeting of FDA Cardiovascular and Renal Drugs Advisory Committee on Prasugrel. Available at: http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/cardiovascularandrenaldrugsadvisorycommittee/ucm181185.pdf . Accessed July 16, 2017
- 6 The FDA Ticagrelor Review of Complete Response. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433Orig1s000MedR.pdf . Accessed July 16, 2017
- 7 NDA 294–886. Cross-discipline Team Leader review on Vorapaxar. April 18, 2014. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204886Orig1s000SumR.pdf . Accessed July 17, 2017
- 8 Serebruany VL, Kim MH, Cabrera-Fuentes HA. , et al. Mortality and cancer after 12 versus 30 months dual antiplatelet therapy. The Korean Outcomes Registry Evaluating Antithrombotics (KOREA). Thromb Haemost 2017; 117 (05) 934-939
- 9 Adverse Event Reporting System (AERS). Available at: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/default.htm . Accessed July 4, 2017
- 10 Duggirala HJ, Tonning JM, Smith E. , et al. Use of data mining at the Food and Drug Administration. J Am Med Inform Assoc 2016; 23 (02) 428-434
- 11 Böhm R, von Hehn L, Herdegen T. , et al. OpenVigil FDA - Inspection of U.S. American Adverse Drug Events Pharmacovigilance Data and Novel Clinical Applications. PLoS One 2016; 11 (06) e0157753
- 12 Serebruany VL, Tomek A, Kim MH, Litvinov O, Marcioniak TA. Aspirin in the Food and Drug Administration Adverse Event Reporting System (FAERS): missing demographics and underreporting. TH Open 2017; 1 (02) e101-e105
- 13 Serebruany VL, Kim MH, Marciniak TA. Worldwide reporting of fatal outcomes after Ticagrelor to the US Food and Drug Administration. Eur Heart J Cardiovasc Pharmacother 2018; 4 (01) 6-9
- 14 Raisch DW, Rafi JA, Chen C, Bennett CL. Detection of cases of progressive multifocal leukoencephalopathy associated with new biologicals and targeted cancer therapies from the FDA's adverse event reporting system. Expert Opin Drug Saf 2016; 15 (08) 1003-1011
- 15 Michel C, Scosyrev E, Petrin M, Schmouder R. Can disproportionality analysis of post-marketing case reports be used for comparison of drug safety profiles?. Clin Drug Investig 2017; 37 (05) 415-422