High Sensitivity Troponin I for Risk Assessment in Patients with Atrial Fibrillation: Insights from the ARISTOTLE Trial

Background — High sensitivity troponin-I (hs-TnI) measurements improves risk assessment for cardiovascular events in many clinical settings, the added value in atrial fibrillation (AF) patients has not been described. Methods and Results —At randomization hs-TnI was analyzed in 14,821 AF patients in the ARISTOTLE trial comparing apixaban with warfarin. The associations between hs-TnI concentrations and clinical outcomes were evaluated using adjusted Cox analysis. The hs-TnI assay detected troponin ( (cid:149) 1.3 ng/L) in 98.5% patients, 50% had levels >5.4, 25% levels >10.1, and 9.2% levels (cid:149) 23 ng/L (the 99 th percentile in healthy). During median 1.9 years follow-up annual rates of stroke or systemic embolism ranged from 0.76% in the lowest hs-TnI quartile to 2.26% in the highest quartile (>10.1ng/L). In multivariable analysis hs-TnI was significantly associated with stroke or systemic embolism, adjusted hazard ratio (HR) 1.98 (1.42-2.78), p=0.0007. hs-TnI was also significantly associated with cardiac death; annual rates ranged from 0.40% to 4.24%, HR 4.52 (3.05-6.70), p<0.0001, in the corresponding groups, and for major bleeding HR 1.44 (1.11-1.86), p=0.0250. Adding hs-TnI levels to the CHA 2 DS 2 VASc-score improved C-statistics from 0.629 to 0.653 for stroke or systemic embolism, and from 0.591 to 0.731 for cardiac death. There were no significant interactions with study treatment. 98.5% and elevated in 9.2% of AF patients. The hs-TnI level stroke, cardiac major bleeding CHA The benefits of apixaban as compared with warfarin are consistent regardless of hs-TnI levels. CoCoConcncnclululusisisionononsss —— TrTrTropopoponononininin I-I-I iiisss dededetetetectctctededed iiinnn elelelevevevatatatededed pppatatatieieientntntsss. TTThehehe hhhss-s-TnTnTnII ooff e e enenndpdpdpoioiointntntss innn ttthhihis study included stroke or syyysstseemmic embolism;m;m ischchhemememic stroke and systemic emmbbobolism, hemomorrrrhahahagigigc stststrororokekeke, mymymyoococaaardddial iiinffarccttioon; alalll-l-ccauususee mmoortrtalalalityy;y; cccararrdidiacacc dddeaeathtt eexcxcxclululudididngngng bbblelleededdininng g g anandd d ototheeer r nononon-n-n-ccacardrddiaiaaccc cccausususesess)); ISISTHTHTH mmmajajjororo bbleleeededeiiningg;g; ccomomompopopossisittetes iinincclclududdeddd troke or syyststemememicicc eeembmbmbolooisssm,m,m, totototalala dddeaeaththth ooor r cacacardrddiaiaacc c dededatatth,h,h aaandndnd mmmyoyoyocacacardrdrdiiialalal iiinfnfnararactctctioioion.n. n. AA blinded detectable in 98.5% and elevated in 9.2% of the patients with non-valvular AF and at least one risk factor for stroke. The relation between hs-TnI and stroke or systemic embolic events, cardiac and total death, and myocardial infarction was gradual and remained highly significant in adjusted analysis. High sensitivity TnI measurements improved risk stratification and risk prediction beyond clinical established models such as the CHA 2 DS 2 VASc score. The present results support the independent prognostic value of troponin I levels concerning the risk of stroke, mortality, composite ischemic events, and major bleeding in patients with atrial fibrillation as recently shown from the RE-LY trial. 6 In the RE-LY biomarker study troponin I was measured in 6189 patients using a contemporary assay (Access AccuTnI assay, Beckman Coulter). High sensitivity troponin assays enables detection of even lower levels of troponin I as well as improvements in the measurement accuracy. By using the Beckman Access AccuTnI assay 57% of the AF patients in RE-LY were shown to have detectable troponin I, and 8% were classified as having troponin I above the 99 th percentile, as compared to 98.5% with detectable and 9.2% above the 99 th percentile with the current Abbott ARCHITECT hs-TnI assay in the present study. The considerably larger number of patients (n=14,821) and the more sensitive troponin assay in the present study as compared to the RELY (n=6,189) biomarker study demonstrated a greater discriminatory power of the hs-TnI than conventional TnI levels concerning all outcome events. In addition there was a larger additive value in the comparison and combination with the CHA 2 DS 2 VASc score. By adding information of hs-TnI to the CHA 2 DS 2 VASc risk score identification of patients at lower as well as higher risk of stroke was improved as compared to either information alone. A substantially lower risk was displayed in those having both a low hs-TnI level ( (cid:148) 3.3 ng/L)