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Ischaemic risk and efficacy of ticagrelor in relation to time from P2Y12 inhibitor withdrawal in patients with prior myocardial infarction: insights from PEGASUS-TIMI 54.
- Source :
- European Heart Journal; 4/7/2016, Vol. 37 Issue 14, p1133-1142, 10p, 3 Charts, 4 Graphs
- Publication Year :
- 2016
-
Abstract
- Aims Ticagrelor reduced major adverse cardiovascular event (MACE) by 15-16% in patients with prior myocardial infarction (MI) in PEGASUS-TIMI 54. We hypothesized that patients who recently discontinued P2Y<subscript>12</subscript> inhibition, even years after MI, may be at particular risk of MACE and may derive particular benefit from continuation or reinitiation of therapy. Methods and results Patients in PEGASUS-TIMI 54 were categorized by time from last P2Y<subscript>12</subscript> inhibitor (days: ≤30, >30-360, >360). The risk of MACE and the efficacy of ticagrelor were compared across categories. In the placebo arm, patients who more recently stopped P2Y<subscript>12</subscript> inhibitor therapy had a greater number of risk factors but still had a higher risk of MACE after multivariable adjustment [≤30 days, hazard ratio (HR)<subscript>adj</subscript> 1.47, 95% confidence interval (CI) 1.12-1.93, P = 0.0051; 30 days-1 year, HR<subscript>adj</subscript> 1.28, 95% CI 0.98-1.67, P = 0.073] compared with those who stopped >1 year prior (P-trend = 0.0097). The benefit of ticagrelor depended on the time from last dose, with HRs (95% CI) for ticagrelor (pooled doses) vs. placebo of 0.73 (0.61-0.87), 0.86 (0.71-1.04), and 1.01 (0.80-1.27), respectively, by category (P-trend for interaction < 0.001). The benefit in those ≤30 days of stopping was similar regardless of time from MI (<2 years, HR 0.73, 95% CI 0.60-0.89 vs. ≥2 years, HR 0.71, 95% CI 0.50-1.00). Conclusion The benefit of ticagrelor for long-term secondary prevention in patients with prior MI and at least one additional risk factor appeared more marked in patients continuing on or re-starting after only a brief interruption of P2Y<subscript>12</subscript> inhibition, when compared with patients who had proved themselves stable more than 2 years from their MI and off P2Y<subscript>12</subscript> inhibitor therapy for more than a year. The increase in bleeding events with ticagrelor was similar regardless of this time interval. For clinicians considering a strategy of prolonged P2Y<subscript>12</subscript> inhibitor therapy in high-risk patients, these data suggest greater benefit in the continuation of such therapy without interruption after MI, rather than re-initiating such therapy in patients who have remained stable for an extended period. Future analyses may help to clarify further the profile of post-MI patients most likely to benefit from uninterrupted dual antiplatelet therapy. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0195668X
- Volume :
- 37
- Issue :
- 14
- Database :
- Complementary Index
- Journal :
- European Heart Journal
- Publication Type :
- Academic Journal
- Accession number :
- 114580289
- Full Text :
- https://doi.org/10.1093/eurheartj/ehv531