Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention with drug eluting stents: meta-analysis of randomised controlled trialsBMJ 2015; 350 doi: https://doi.org/10.1136/bmj.h1618 (Published 16 April 2015) Cite this as: BMJ 2015;350:h1618
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Re: Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention with drug eluting stents: meta-analysis of randomised controlled trials
The authors of the excellent meta-analysis of optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with drug eluting stents conclude that “The increase in all cause but not cardiovascular death with extended DAPT requires further investigation.” They appear to be unaware of the evidence suggesting that drugs that cause bleeding are associated with higher rates of solid cancers and of cancer deaths. Patient-level meta-analyses of all antiplatelet and anticoagulant trials submitted to the U.S. Food and Drug Administration (FDA) strongly support the association of excess bleeding with excess solid cancers. The authors do note the excess of cancer-related deaths observed in the DAPT trial. However, both the authors’ meta-analysis and the FDA meta-analyses were completed prior to the publication of the PEGASUS trial results. PEGASUS, which tested two dosages of ticagrelor against placebo, showed an increasing dose-response relationship for malignancy deaths. In PEGASUS there were 53 malignancy deaths in the placebo arm, 64 in the 60mg arm, and 77 in the 90mg arm. The two most recent antiplatelet megatrials, DAPT and PEGASUS, document that the excess mortality with long term DAPT is due to cancer.
Why is the relationship between drugs that cause bleeding and cancer not widely appreciated? The U.S. FDA, despite a website banner proclaiming “Protecting and Promoting Your Health”, has refused to release the evidence from its reviewer’s analyses documenting the association and has refused to discuss the issue at an open forum. The FDA heavily censored the meta-analyses referenced above , claiming that the censored material represented confidential commercial information or trade secrets. The censored material included data from the DAPT trial, supported in part by public tax dollars, and the FDA reviewer’s pre-specified methodology used for the meta-analyses, not commercial information or trade secrets. The situation is worse for the release of information for the related issue of whether angiotensin receptor blocker use is associated with cancer: The FDA has refused to release the patient-level meta-analyses documenting an association, possibly because it publicized that angiotensin receptor blocker use is not associated with cancer based on study-level meta-analyses of drug company-submitted cancer counts in which the FDA failed to count lung carcinomas as cancers, in addition to other mistakes. If we are to understand better the risks and benefits of the drugs we take, the FDA must release all of the relevant information and truly protect and promote public health.
1 Navarese EP, Andreotti F, Schulze V, et al. Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention with drug eluting stents: meta-analysis of randomised controlled trials. BMJ 2015;350. doi:10.1136/bmj.h1618
2 Marciniak TA. FDA clinical review: Antiplatelet and anticoagulant drugs cancer risk. 2014. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022307s000TOC.cfm Pages 7-70. (accessed 17 Mar2015).
3 Mauri L, Kereiakes DJ, Yeh RW, et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med 2014;371:2155–66. doi:10.1056/NEJMoa1409312
4 Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med Published Online First: 14 March 2015. doi:10.1056/NEJMoa1500857
5 FDA. FDA briefing document: readjudication of the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of glycemia in Diabetes trial (RECORD). 2013. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMateria... Page 346. (accessed 18 Apr2015).
Competing interests: No competing interests