Antiplatelet and anticoagulant therapy in patients with acute coronary syndromes and atrial fibrillation

Abstract

Dual antiplatelet therapy (DAPT), consisting of aspirin and a P2Y12 receptor antagonist, is the standard of care following an acute coronary syndrome (ACS) presentation, and oral anticoagulation (OAC) is standard of care for stroke prevention in atrial fibrillation (AF) patients. In patients with AF who present with an ACS, it is not clear whether the combination of DAPT and OAC, known as triple therapy (TT), should be the preferred treatment strategy, or whether DAPT alone is optimal. The first two studies in this thesis examined contemporary antiplatelet/anticoagulant management in New Zealand. The first study examined management of 93 ACS patients with AF from a single-centre. We found DAPT was the preferred treatment regimen, and no TT use was observed. Decisions regarding therapy did not appear to be based on assessments of stroke or bleeding risk. In the second study, we utilised the national ANZACS-QI registry, and examined pharmacy prescription data for 610 ACS patients who underwent percutaneous coronary intervention (PCI) with a history of AF. In this cohort DAPT was again the most common discharge regimen followed by TT, and their use was not driven by stroke risk (CHA2DS2VASc scores). Rates of DAPT and TT declined markedly over the 12 months following the ACS event. On the basis of these two studies we concluded that no consistent treatment strategy was evident for the management of ACS patients with AF. A systematic literature review was then undertaken to identify optimal therapy. We selected papers describing treatment regimens and one-year outcomes for patients with AF and either ACS or PCI. The inclusion of stable PCI patients was necessary as the majority of literature featured mixed cohorts of ACS or stable coronary disease undergoing PCI. The identified literature was entirely observational in nature and the overall quality was poor. The largest studies reported that TT offered significant reductions in stroke over DAPT, and a consistent increase in bleeding associated with TT was reported. On the basis that the available literature did not offer clear guidance on when the benefits associated with stroke reduction with TT would be greater than the harm associated with excess bleeding, we constructed a decision analysis model. This model addressed likely thresholds at which TT stroke reduction may exceed harm from bleeding. Under most modelled scenarios TT was not preferred above DAPT at CHA2DS2VASc 2, and only outperformed DAPT when stroke risk was high in the CHA2DS2VASc 3-5 range. Given the importance of bleeding in determining the net clinical benefit of DAPT versus TT we examined how accurately bleeding events could be predicted in a cohort of 1000 acute myocardial infarction patients. We examined the ACS bleeding scores CRUSADE and ACTION as well as low platelet reactivity (LPR) to predict one-year TIMI major and minor bleeding. We found that neither score nor LPR accurately predicted one-year bleeding events. The clinical problem of optimal antiplatelet/anticoagulant therapy in ACS patients with AF remains significant. Our data suggests that at low stroke risks DAPT is probably the treatment of choice, with TT becoming more acceptable at higher stroke risk. Accurate classification of bleeding risk in this population is needed to minimise potential harms associated with TT.