Two-year results from Onyx ONE clear in patients with high bleeding risk on one-month DAPT with and without intracoronary imaging.

BACKGROUND: Patients with high bleeding risk (HBR) are often treated with abbreviated dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) to reduce bleeding risk, however this strategy is associated with an increase in ischemic events, especially if the acute PCI result is suboptimal. We compared clinical outcomes among patients with HBR treated with 1-month DAPT who underwent intravascular ultrasound (IVUS)- or optical coherence tomography (OCT)-guided PCI versus those who underwent angiography-guided PCI without intravascular imaging. METHODS: The Onyx ONE Clear study includes patients with HBR from the Onyx ONE US/Japan and Onyx ONE randomized studies who were treated with the Resolute Onyx zotarolimus-eluting stent. The primary endpoint was the composite of cardiac death (CD) or myocardial infarction (MI) between 1 month and 2 years after PCI. Propensity-score adjustments and matching were performed for differences in baseline and procedural characteristics between groups. RESULTS: Among the 1507 patients in Onyx ONE Clear, 271 (18.0 %) had IVUS or OCT used during PCI (Imaging-guided group) and 1236 (82.0 %) underwent Angiography-guided PCI (Angio-guided group). Imaging-guided patients were less likely to present with atrial fibrillation, acute coronary syndrome, and left ventricle ejection fraction ≤35 %. Conversely, Imaging-guided patients were more likely to have complex (ACC/AHA type B2/C), longer, and heavily calcified lesions. Between 1 month and 2 years, the composite rate of CD or MI was similar between Imaging-guided and Angio-guided patients (9.9 % vs. 12.4 %, P = 0.33). There was also no difference between groups after adjustment; (P = 0.56). However, CD was significantly lower among Imaging-guided patients (2.7 % vs. 6.1 %, P = 0.048). There were no between-group differences in MI or stent thrombosis. Propensity score matching results were similar. CONCLUSION: Despite higher lesion complexity, using intravascular imaging guidance for PCI between 1-month and 2-years follow-up had comparable outcomes with angiographic guidance alone in patients with HBR treated with 1-month DAPT. (ClinicalTrials.gov: Identifier: NCT03647475 and NCT03344653). NON-STANDARD ABBREVIATIONS AND ACRONYMS: BARC: Bleeding Academic Research Consortium; DAPT: dual antiplatelet therapy; DES: drug-eluting stent; HBR: high bleeding risk; IVUS: intravascular ultrasound; OCT: optical coherence tomography; SAPT: single antiplatelet therapy.

Diabetes mellitus: the major risk factor in unstable coronary artery disease even after consideration of the extent of coronary artery disease and benefits of revascularization.

OBJECTIVES: This study was designed to study the influence of diabetes on the outcome of unstable coronary artery disease (CAD). BACKGROUND: Diabetes mellitus is a major contributor to CAD. Despite improvement in the management of patients with unstable coronary syndromes, this condition is still linked to a substantially increased mortality and morbidity among diabetic patients. Recent evidence advocates early revascularization in unstable coronary syndromes. Diabetic patients subjected to coronary interventions under stable conditions have a higher risk for complications and a more dismal prognosis than nondiabetic subjects. Accordingly, it is of considerable interest to obtain further information regarding the best possible management of diabetic patients with unstable CAD. METHODS: A total of 2158 patients without and 299 with diabetes mellitus were randomized to an early invasive or a noninvasive strategy. The severity of CAD was expressed as the number and extent of vessel involvement. RESULTS: Three-vessel disease was diagnosed in 42% of diabetic and 31% of nondiabetic patients (p = 0.006). The percentages of patients with ST-depression and troponin-T >0.03 microg/l at admission were comparable among diabetic and nondiabetic patients. Mortality and reinfarction after 12 months were more frequent among diabetic than nondiabetic patients in both treatment groups. Diabetes remained a strong independent predictor for death and myocardial infarction in multivariable analysis. The invasive strategy reduced event rate in nondiabetic patients from 12.0% to 8.9% (odds ratio [OR] = 0.72; confidence interval [CI] 0.54 to 0.95; p = 0.019) and in diabetic patients from 29.9% to 20.6% (OR 0.61; CI 0.36 to 1.04; p = 0.066). In a multivariate analysis including the extent of CAD, diabetes remained a strong independent predictor of the combined end point (relative risk [RR] 2.40; CI 1.47 to 3.91; p = 0.0001) and of mortality (RR 5.43; CI 2.09 to 14.12; p = 0.001). CONCLUSIONS: An invasive strategy improved outcome for both diabetic and nondiabetic patients with unstable CAD. However, diabetes mellitus remained an independent and important risk factor for death and myocardial infarction in the invasive group. Thus, factors beyond the extent of flow-limiting coronary lesions are of considerable importance for outcome in diabetic subjects with unstable coronary syndromes.

Effects of an early invasive strategy on ischemia and exercise tolerance among patients with unstable coronary artery disease.

BACKGROUND: An early invasive approach after an episode of unstable coronary artery disease has beneficial effects on mortality and myocardial infarction, but its effects on exercise capacity and ischemia have not been investigated. METHODS: In the Fast Revascularisation during InStability in Coronary disease (FRISC) II trial, 2457 patients with unstable coronary artery disease were assigned randomly to an early invasive or noninvasive strategy. A symptom-limited bicycle exercise test was performed before discharge in the noninvasive group and after 3 months in both groups. RESULTS: At 3 months, 86% (1046/1222) of the patients in the invasive group and 81% (995/1235) in the noninvasive group performed the exercise test. Before the test, revascularization had been performed in 78% (n = 819) of these patients in the invasive group compared with 28% (n = 281) of those in the noninvasive group. The mean (+/- SD) exercise capacity was higher (6.4 +/- 1.9 vs. 6.2 +/- 1.9 metabolic equivalents [METS], P <0.01), and the occurrence of ischemia lower (23% [229/1004] vs. 36% [352/966], P <0.001) in the invasive group. In the noninvasive group, 882 patients performed an exercise test both predischarge and at 3 months. If a revascularization procedure was performed (n = 210), exercise tolerance increased from 5.1 +/- 1.4 to 6.0 +/- 1.8 METS (P <0.001) and the number of patients with ST depression decreased from 65% (131/203) to 31% (63/203) (P <0.001). Without revascularization (n = 670), exercise tolerance increased from 5.9 +/- 2.2 to 6.3 +/- 1.9 METS (P <0.001), and there were no differences in the occurrence of ischemia. CONCLUSION: In unstable coronary artery disease, an invasive strategy improves exercise tolerance and reduces exercise-induced ischemia.

The prognostic and therapeutic implications of increased troponin T levels and ST depression in unstable coronary artery disease: the FRISC II invasive troponin T electrocardiogram substudy.

BACKGROUND: In unstable coronary artery disease, both increased troponin T level and occurrence of ST-segment depression are associated with a worse prognosis. In the Fast Revascularisation in InStability in Coronary disease trial II invasive study, we evaluated whether the troponin T level, alone and combined with ST depression, identified more severe coronary artery disease or a greater efficacy of an early invasive strategy. METHODS: In the study, 2457 patients with unstable coronary artery disease were randomized to early invasive or noninvasive strategy. Troponin T value and admission electrocardiogram results were available in 2286 patients. RESULTS: In the noninvasive cohort, death or myocardial infarction occurred in 16.6% with troponin T level > or =0.03 microg/L versus 8.5% with troponin T level < 0.03 microg/L (P <.001). In the invasive group, 49% of patients with both ST depression and troponin T level > or =0.03 microg/L had 3-vessel or left main disease compared with 17% if neither finding was present (P <.001). The invasive strategy reduced death/myocardial infarction at 12 months in the cohort with both ST depression and troponin T level > or =0.03 microg/L from 22.1% to 13.2% (risk ratio, 0.60; 95% confidence interval, 0.43 to 0.82; P =.001). In the cohort with either ST depression or troponin T level > or =0.03 microg/L or neither of these findings, the absolute gain of the invasive strategy was smaller and more uncertain. CONCLUSION: Patients with unstable coronary artery disease with the combination of troponin T level > or =0.03 microg/L and ST depression have a poor prognosis and, in half of the cases, 3-vessel or left main disease. In these patients, an early invasive strategy will substantially reduce death/myocardial infarction.

Clinical performance of three cardiac troponin assays in patients with unstable coronary artery disease (a FRISC II substudy).

The assay of cardiac-specific troponins (cTroponins) is a sensitive and specific means to diagnose myocardial injury. Several assays for the measurement of cardiac-specific troponin I (cTnI), but only 1 for the assay of cardiac specific troponin T (cTnT), are commercially available. The aim of this study was to compare 3 of these assays (i.e., Access AccuTnI [cTnI], AxSym [cTnI], and Elecsys 3(rd) generation [cTnI]) and their clinical performances in a group of patients (n = 1,763) with unstable coronary artery disease (Fragmin and fast Revascularisation during InStability in Coronary artery disease [FRISC II] trial). Clinical events after 1-year follow-up, such as death and death and/or acute myocardial infarction, were recorded and the effects of invasive or noninvasive treatment evaluated in relation to cTroponin levels. Overall the 2 cTnI methods showed good correlation (r(s) = 0.96), whereas correlations to the cTnT assay were somewhat lower (r(s) = 0.93). Patients with nonelevated levels, as measured with any of the 3 biomarkers, had a significantly better prognosis than patients with elevated levels (p <0.001). A cohort of 10% to 12.4% of patients with a poor prognosis was identified only by the Access AccuTnI assay. Invasive treatment reduced clinical events only in the group of patients with elevated cTroponin levels. We conclude that stratification of patients with unstable coronary artery disease by means of cTroponin measurements is important in clinical management. It is also apparent that assays with superior sensitivity, such as the Access AccuTnI, identify more patients with poor prognosis who are candidates for early invasive procedures.