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Response to letter: Duration of dual antiplatelet therapy following drug-eluting coronary stents: Longer or shorter?
International Journal of Cardiology 202 (2016) 938
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Correspondence
Response to letter: Duration of dual antiplatelet therapy following drug-eluting coronary stents: Longer or shorter? James Cockburn ⁎, David Hildick-Smith Sussex Cardiac Centre, Brighton, UK
a r t i c l e
i n f o
Article history: Received 16 October 2015 Accepted 18 October 2015 Available online 20 October 2015
We read with interest the response to our paper [1] by Fan et al., and thank the authors for their insightful comments [2]. We concur that that the duration of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) remains an enigma. Just as the waters were clearing with the results of studies discussed in their letter suggesting that 6 months DAPT was probably sufficient along came the Navarese meta-analysis just in time to muddy the waters again [3]. This is a very complete meta-analysis for which the authors should be congratulated. Firstly, it has used multiple (n = 10) randomized control trials and excluded small observational studies with a total of 32,287 patients. 7975 were randomly allocated to short term regimens (b12 months) and 8196 to extended regimens (N 12 months), with 16,116 patients constituting the 12 month control group. Secondly, all the randomized trials were contemporary, the oldest dating back only as far as 2012. Therefore they are most likely to reflect both contemporary antiplatelet medication practice (Clopidogrel and aspirin n = 5; prasugrel or ticagrelor n = 3 and 2, respectively) and include modern drug-eluting stents (DES), (≥2nd generation DES). Thirdly, all cardiovascular endpoints were hard and bleeding endpoints used a combination of those within the individual studies and also additional TIMI bleeding score determined by the authors. The results however were very interesting. Compared with standard 12 month DAPT regimen, a short term course (b12 months) was associated with a significant reduction in major bleeding (odds ratio 0.58 (95% CI 0.36 to 0.92); P = 0.02) with no significant differences in ischemic or thrombotic outcomes, which was what we were all hoping for.
DOI of original article: http://dx.doi.org/10.1016/j.ijcard.2015.09.063. ⁎ Corresponding author. E-mail address: [email protected] (J. Cockburn).
http://dx.doi.org/10.1016/j.ijcard.2015.10.162 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
However, an extended regimen (N12 month DAPT) vs. standard 12 month DAPT yielded a significant reduction in the odds of myocardial infarction (0.53 (95% CI 0.42 to 0.66); P b 0.001) and definitive/probable stent thrombosis, including very late thrombosis (N1 year) (0.33 (95% CI 0.21 to 0.51); P b 0.001), but at the expense of more major bleeding (1.62 (95% CI 1.26 to 2.09); P b 0.001). To confuse things further all cause but not cardiovascular death was also significantly increased (1.30 (95% CI 1.02 to 1.66); P = 0.03, (number needed to harm 238), in the extended regimen group. Maybe any form of bleeding is bad for you? How do we interpret this then? Once again it appears a difficult balancing act of ischemic protection with extended therapy at the price of increased bleeding risk. It appears that the currently recommended 12 month duration of dual antiplatelet therapy reflects nothing more than a compromise between the two issues above. Maybe the answer could be that the duration of DAPT therapy should depend on an individual's ischemia and bleeding risk to whether or not they should receive a shorter or extended DAPT regimen. Time and further trials will only tell. Conflict of interest We both have no conflicts pertaining to this publication. References [1] J. Cockburn, N. Pareek, P. Poliacikova, S. Saraf, R. Williams, G. Dhillon, et al., Clinical outcomes with 6 months dual antiplatelet therapy after implantation of biolimusA9 drug eluting coronary stents, Int. J. Cardiol. 172 (2014) 185–189. [2] Z. Fan, J. Yanga, C. Yang, J. Yang, P. Zeng, X. Guo, Duration of dual antiplatelet therapy following drug-eluting coronary stents: longer or shorter? 2015. [3] Navarese EP, Andreotti F, Schulze V, Kołodziejczak M, Buffon B, Brouwer M, Costa F, Kowalewski M, Parati G Lip G, Kelm G, Valgimigli M. Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention with drug eluting stents: meta-analysis of randomised controlled trials. BMJ 2015;350:h1618 | doi: http://dx. doi.org/10.1136/bmj.h1618.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Correspondence
Response to letter: Duration of dual antiplatelet therapy following drug-eluting coronary stents: Longer or shorter? James Cockburn ⁎, David Hildick-Smith Sussex Cardiac Centre, Brighton, UK
a r t i c l e
i n f o
Article history: Received 16 October 2015 Accepted 18 October 2015 Available online 20 October 2015
We read with interest the response to our paper [1] by Fan et al., and thank the authors for their insightful comments [2]. We concur that that the duration of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) remains an enigma. Just as the waters were clearing with the results of studies discussed in their letter suggesting that 6 months DAPT was probably sufficient along came the Navarese meta-analysis just in time to muddy the waters again [3]. This is a very complete meta-analysis for which the authors should be congratulated. Firstly, it has used multiple (n = 10) randomized control trials and excluded small observational studies with a total of 32,287 patients. 7975 were randomly allocated to short term regimens (b12 months) and 8196 to extended regimens (N 12 months), with 16,116 patients constituting the 12 month control group. Secondly, all the randomized trials were contemporary, the oldest dating back only as far as 2012. Therefore they are most likely to reflect both contemporary antiplatelet medication practice (Clopidogrel and aspirin n = 5; prasugrel or ticagrelor n = 3 and 2, respectively) and include modern drug-eluting stents (DES), (≥2nd generation DES). Thirdly, all cardiovascular endpoints were hard and bleeding endpoints used a combination of those within the individual studies and also additional TIMI bleeding score determined by the authors. The results however were very interesting. Compared with standard 12 month DAPT regimen, a short term course (b12 months) was associated with a significant reduction in major bleeding (odds ratio 0.58 (95% CI 0.36 to 0.92); P = 0.02) with no significant differences in ischemic or thrombotic outcomes, which was what we were all hoping for.
DOI of original article: http://dx.doi.org/10.1016/j.ijcard.2015.09.063. ⁎ Corresponding author. E-mail address: [email protected] (J. Cockburn).
http://dx.doi.org/10.1016/j.ijcard.2015.10.162 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
However, an extended regimen (N12 month DAPT) vs. standard 12 month DAPT yielded a significant reduction in the odds of myocardial infarction (0.53 (95% CI 0.42 to 0.66); P b 0.001) and definitive/probable stent thrombosis, including very late thrombosis (N1 year) (0.33 (95% CI 0.21 to 0.51); P b 0.001), but at the expense of more major bleeding (1.62 (95% CI 1.26 to 2.09); P b 0.001). To confuse things further all cause but not cardiovascular death was also significantly increased (1.30 (95% CI 1.02 to 1.66); P = 0.03, (number needed to harm 238), in the extended regimen group. Maybe any form of bleeding is bad for you? How do we interpret this then? Once again it appears a difficult balancing act of ischemic protection with extended therapy at the price of increased bleeding risk. It appears that the currently recommended 12 month duration of dual antiplatelet therapy reflects nothing more than a compromise between the two issues above. Maybe the answer could be that the duration of DAPT therapy should depend on an individual's ischemia and bleeding risk to whether or not they should receive a shorter or extended DAPT regimen. Time and further trials will only tell. Conflict of interest We both have no conflicts pertaining to this publication. References [1] J. Cockburn, N. Pareek, P. Poliacikova, S. Saraf, R. Williams, G. Dhillon, et al., Clinical outcomes with 6 months dual antiplatelet therapy after implantation of biolimusA9 drug eluting coronary stents, Int. J. Cardiol. 172 (2014) 185–189. [2] Z. Fan, J. Yanga, C. Yang, J. Yang, P. Zeng, X. Guo, Duration of dual antiplatelet therapy following drug-eluting coronary stents: longer or shorter? 2015. [3] Navarese EP, Andreotti F, Schulze V, Kołodziejczak M, Buffon B, Brouwer M, Costa F, Kowalewski M, Parati G Lip G, Kelm G, Valgimigli M. Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention with drug eluting stents: meta-analysis of randomised controlled trials. BMJ 2015;350:h1618 | doi: http://dx. doi.org/10.1136/bmj.h1618.