Performance of the European Society of Cardiology 0/1-Hour, 0/2-Hour, and 0/3-Hour Algorithms for Rapid Triage of Acute Myocardial Infarction : An International Collaborative Meta-analysis.

BACKGROUND: The 2020 European Society of Cardiology (ESC) guidelines recommend using the 0/1-hour and 0/2-hour algorithms over the 0/3-hour algorithm as the first and second choices of high-sensitivity cardiac troponin (hs-cTn)-based strategies for triage of patients with suspected acute myocardial infarction (AMI). PURPOSE: To evaluate the diagnostic accuracies of the ESC 0/1-hour, 0/2-hour, and 0/3-hour algorithms. DATA SOURCES: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from 1 January 2011 to 31 December 2020. (PROSPERO: CRD42020216479). STUDY SELECTION: Prospective studies that evaluated the ESC 0/1-hour, 0/2-hour, or 0/3-hour algorithms in adult patients presenting with suspected AMI. DATA EXTRACTION: The primary outcome was index AMI. Twenty unique cohorts were identified. Primary data were obtained from investigators of 16 cohorts and aggregate data were extracted from 4 cohorts. Two independent authors assessed each study for methodological quality. DATA SYNTHESIS: A total of 32 studies (20 cohorts) with 30 066 patients were analyzed. The 0/1-hour algorithm had a pooled sensitivity of 99.1% (95% CI, 98.5% to 99.5%) and negative predictive value (NPV) of 99.8% (CI, 99.6% to 99.9%) for ruling out AMI. The 0/2-hour algorithm had a pooled sensitivity of 98.6% (CI, 97.2% to 99.3%) and NPV of 99.6% (CI, 99.4% to 99.8%). The 0/3-hour algorithm had a pooled sensitivity of 93.7% (CI, 87.4% to 97.0%) and NPV of 98.7% (CI, 97.7% to 99.3%). Sensitivity of the 0/3-hour algorithm was attenuated in studies that did not use clinical criteria (GRACE score <140 and pain-free) compared with studies that used clinical criteria (90.2% [CI, 82.9 to 94.6] vs. 98.4% [CI, 88.6 to 99.8]). All 3 algorithms had similar specificities and positive predictive values for ruling in AMI, but heterogeneity across studies was substantial. Diagnostic performance was similar across the hs-cTnT (Elecsys; Roche), hs-cTnI (Architect; Abbott), and hs-cTnI (Centaur/Atellica; Siemens) assays. LIMITATION: Diagnostic accuracy, inclusion and exclusion criteria, and cardiac troponin sampling time varied among studies. CONCLUSION: The ESC 0/1-hour and 0/2-hour algorithms have higher sensitivities and NPVs than the 0/3-hour algorithm for index AMI. PRIMARY FUNDING SOURCE: National Taiwan University Hospital.

Prognostic value of elevated high-sensitivity cardiac troponin T in patients admitted to an emergency department with atrial fibrillation.

Aims: Elevated levels of high-sensitivity cardiac troponin T (hsTnT) indicate underlying heart disease and are known to predict adverse outcomes in various patient populations. Their role in atrial fibrillation (AF) is still under debate. Methods and results: This retrospective study included 2898 consecutive patients presenting with AF to the emergency department of the Department of Cardiology, Heidelberg University Hospital. Multivariable Cox regression was used to assess associations between hsTnT and mortality. Elevated hsTnT levels were associated with increased risk of all-cause mortality in all patients with AF, as well as in each subtype of AF. After adjustment for multiple risk factors, both detectable hsTnT below the 99th percentile (5-14 ng/L, adjusted hazard ratio (HR): 4.86 [95% CI: 1.77-13.34], P = 0.002) and elevated hsTnT (>14 ng/L, adjusted HR: 13.42 [95% CI: 4.95-36.40], P < 0.001) were associated with a higher risk of mortality in patients with AF, compared to undetectable hsTnT (<5 ng/L). Elevated hsTnT was also associated with higher mortality after exclusion of patients with myocardial infarction, as well as in the subgroup of patients with AF as main admission diagnosis. The inclusion of hsTnT significantly improved the performance of the multivariable model for mortality prediction. Conclusion: Elevated hsTnT levels are associated with higher mortality in patients with AF, and provide added prognostic information independent of major cardiovascular risk factors and clinical characteristics. Measurement of hsTnT should be considered for risk assessment in patients presenting to an emergency department with AF. Clinical trial registration: http://www.clinicaltrials.gov; Unique identifier: NCT02542189.

Prognostic value of circulating microRNAs compared to high-sensitivity troponin T in patients presenting with suspected acute coronary syndrome to the emergency department.

BACKGROUND: To evaluate the prognostic value of eleven microRNAs (miRNAs) compared to high-sensitivity Troponin T (hs-cTnT) in patients presenting with suspected acute coronary syndrome (ACS) to the emergency department (ED). METHODS: 1,042 patients presenting between August 2014 and April 2017 were included. Expression levels of eleven microRNAs (miR-21-5p, miR-22-3p, miR-29a-3p, miR-92a-3p, miR-122-5p, miR-126-3p, miR-132-3p, miR-133a-3p, miR-134-5p, miR-191-3p, and miR-423-5p) were determined using RT-qPCR. All-cause mortality (ACM) and a composite of ACM, acute myocardial infarction (AMI) and stroke were defined as endpoints. RESULTS: During a median follow-up of 399 (P25-P75: 381-525) days 58 patients (5.6%) died. The composite endpoint occurred in 86 patients (8.3%). Different expression levels of miR-21-5p (median, P25-P75: 5.28 [5.14-5.51] vs. 5.16 [4.97-5.35], p = 0.0033) and miR-122-5p (median, P25-P75: 5.17 [4.81-5.49] vs. 5.35 [5.01-5.69], p = 0.0184) were observed in patients who died compared to survivors. ROC-optimized cutoff of miR-21-5p (HR, P25-P75: 3.3 [1.2-9.4], p = 0.0239), but not miR-122-5p (HR, P25-P75: 0.4 [0.2-0.8], p = 0.0116), was predictive for all-cause mortality, even after adjustment in a multivariate model. Nevertheless, addition of miR-21-5p and miR-122-5p decreased prognostic accuracy of hs-cTnT for all-cause mortality (△AUC: 0.112, p = 0.0159). Hs-cTnT admission values had a high prognostic value for ACM (AUC [95%CI] = 0.794 [0.751-0.837]) and the composite of ACM, AMI and stroke (AUC [95%CI] = 0.745 [0.695-0.794]). CONCLUSIONS: Despite a different expression depending on outcomes miR-21-5p and miR-122-5p do not add prognostic information to hs-cTnT in patients presenting with suspected ACS to the ED.

Validation of two severity scores as predictors for outcome in Coronavirus Disease 2019 (COVID-19).

BACKGROUND: An established objective and standardized reporting of clinical severity and disease progression in COVID-19 is still not established. We validated and compared the usefulness of two classification systems reported earlier-a severity grading proposed by Siddiqi and a system from the National Australian COVID-19 guideline. Both had not been validated externally and were now tested for their ability to predict complications. METHODS: In this retrospective, single-centre observational study, patients hospitalized with confirmed COVID-19 across all severity stages were enrolled. The clinical severity was graded at admission and during hospitalization. Multivariate Cox regression was used to identify independent risk factors for mortality, a composite primary (mortality, incident acute respiratory distress syndrome, incident mechanical ventilation), a secondary endpoint (mortality, incident acute myocardial injury, incident venous thrombosis, pulmonary embolism or stroke) and progression of severity grades. RESULTS: Of 109 patients 17 died, 31 and 48 developed the primary and secondary endpoint, respectively. Worsening of the severity grade by at least one stage occurred in 27 and 28 patients, respectively. Siddiqi and Australian classification were identified as independent predictors for the primary endpoint (adjusted hazard ratio (aHR) 2.30, p<0.001 and aHR 2.08, p<0.001), for the secondary endpoint (aHR 2.12, p<0.001 and aHR 1.79, p<0.001) and mortality (aHR 2.30, p = 0.071 and aHR 1.98, p = 0.017). Both classification systems showed very good agreement regarding initial grading and good agreement regarding progression of severity stages. CONCLUSIONS: Standardized and objective severity grading is useful to unequivocally stratify patients presenting with COVID-19 for their individual risk of complications.

Low-Level Elevations of Procalcitonin Are Associated with Increased Mortality in Acute Heart Failure Patients, Independent of Concomitant Infection.

We aimed to evaluate the prognostic value of procalcitonin (PCT) in acute heart failure (AHF) patients, especially in those without underlying infection. We enrolled patients presenting with acute dyspnea to the emergency department (ED) of Heidelberg University Hospital and studied the prognostic role of PCT on all-cause death. Of 312 patients, AHF was diagnosed in 139 patients. Of these, 125 patients had AHF without signs of infection, and 14 had AHF complicated by respiratory or other infection. The optimal prognostic PCT cutoff value for mortality prediction was calculated by a receiver operating characteristics curve. In patients with AHF, the prognostic PCT cutoff value was 0.08 ng/mL. The Kaplan-Meier survival analysis showed that AHF patients with PCT values > 0.08 ng/mL had a higher all-cause mortality at 120 days than those with PCT values ≤ 0.08 ng/mL (log-rank p = 0.0123). Similar results could be obtained after subdivision into AHF patients with and without signs of overt infection. In both cases, mortality was higher in patients with PCT levels above the prognostic PCT cutoff than in those with values ranging below this threshold. Moreover, we show that the prognostic PCT cutoff values for mortality prediction ranged below the established PCT cutoff for the guidance of antibiotic therapy. In conclusion, the data of our study revealed that low-level elevations of PCT were associated with an increased mortality in patients with AHF, irrespective of concomitant respiratory or other infection. PCT should thus be further used as a marker in the risk stratification of AHF.

Diagnostic value of circulating microRNAs compared to high-sensitivity troponin T for the detection of non-ST-segment elevation myocardial infarction.

AIMS: To assess the diagnostic value of microRNAs (miRNAs) for the detection of non-ST-segment elevation myocardial infarction (NSTEMI). METHODS AND RESULTS: A total of 1042 patients presenting between August 2014 and April 2017 to the emergency department with the suspected acute coronary syndrome were included. Non-ST-segment elevation myocardial infarction was diagnosed per criteria of the fourth Universal definition of myocardial infarction (UDMI) using high-sensitivity troponin T (hs-cTnT). Expression levels of eleven microRNAs (miR-21, miR-22, miR-29a, miR-92a, miR-122, miR-126, miR-132, miR-133, miR-134, miR-191, and miR-423) were determined using RT-qPCR. Discrimination of NSTEMI was assessed for individual and a panel of miRNAs compared to the hs-cTnT reference using C-statistics and reclassification analysis. NSTEMI was diagnosed in 137 (13.1%) patients. The area under the curve (AUC) of the hs-cTnT based reference was 0.937. In a multivariate model, three miRNAs (miR-122, miR-133, and miR-134) were found to be associated with NSTEMI with AUCs between 0.506 and 0.656. A panel consisting of these miRNAs revealed an AUC of 0.662 for the diagnosis of NSTEMI. The AUC of the combination of the miRNA panel and troponin reference was significantly lower than the reference standard (AUC: 0.897 vs. 0.937, P = 0.006). Despite a significant improvement of NSTEMI reclassification measured by IDI and NRI, miRNAs did not improve the specificity of hs-cTnT kinetic changes for the diagnosis of NSTEMI (ΔAUC: 0.04). CONCLUSION: Although single miRNAs are significantly associated with the diagnosis of NSTEMI a miRNA panel does not add diagnostic accuracy to the hs-cTnT reference considering baseline values and kinetic changes as recommended by the fourth version of UDMI. CLINICAL TRIALS IDENTIFIER: NCT02116153.

Effects of crowding in the emergency department on the diagnosis and management of suspected acute coronary syndrome using rapid algorithms: an observational study.

OBJECTIVES: Fast diagnostic algorithms using high-sensitivity troponin (hsTn) in suspected acute coronary syndrome (ACS) are regarded as beneficial to expedite diagnosis and safe discharge of patients in crowded emergency departments (ED). This study investigates the effects of crowding on process times related to the diagnostic protocol itself or other time delays, and outcomes. DESIGN: Prospective single-centre observational study. SETTING: ED (Germany). PARTICIPANTS: Final study population of 2525 consecutive patients with suspected ACS within 12 months, after exclusion of patients with ST-elevation myocardial infarction, missing blood samples, referral from other hospitals or repeated visits. INTERVENTIONS: Use of fast algorithms as per 2015 European Society of Cardiology guidelines. MAIN OUTCOME MEASURES: Crowding was defined as mismatch between patient numbers and monitoring capacities, or mean physician time per case, categorised as normal, high and very high crowding. Outcome measures were length of ED stay, direct discharge from ED, laboratory turn around times (TAT), utilisation of fast algorithms, absolute and relative non-laboratory time, as well as mortality. RESULTS: Crowding was associated with increased length of ED stay (3.75-4.89 hours, p<0.001). While median TAT of the first hsTnT increased (53-57 min, p<0.001), total TAT of serial hsTnT did not increase significantly with higher crowding (p=0.170). Lower utilisation of fast algorithms (p=0.009) and increase of additional hsTnT measurements after diagnosis (p=0.001) were observed in higher crowding. Most importantly, crowding was significantly associated with prolonged absolute (p<0.001), and particularly relative non-laboratory time (63.3%-71.3%, p<0.001). However, there was no significant effect of crowding on mortality, even after adjustment for relevant clinical variables. CONCLUSIONS: Process times, and particularly non-laboratory times, are prolonged in a crowded ED diminishing some positive effects of fast diagnostic algorithms in suspected ACS. Higher crowding levels were not significantly associated with higher all-cause mortality rates. TRIAL REGISTRATION NUMBER: NCT03111862.

Prognostic Value of Elevated Copeptin and High-Sensitivity Cardiac Troponin T in Patients with and without Acute Coronary Syndrome: The ConTrACS Study.

AIMS: We aimed to assess the prognostic role of copeptin in patients presenting to the emergency department with acute symptoms and increased high-sensitivity cardiac troponin T. METHODS: A total of 3890 patients presenting with acute symptoms to the emergency department of Heidelberg University Hospital were assessed for increased hs-cTnT (>14 ng/L) from three cohorts: the Heidelberg Acute Coronary Syndrome (ACS) Registry (n = 2477), the BIOPS Registry (n = 320), and the ACS OMICS Registry (n = 1093). In a pooled analysis, 1956 patients remained, comprising of 1600 patients with ACS and 356 patients with non-ACS. RESULTS: Median follow-up was 1468 days in the ACS cohort and 709 days in the non-ACS cohort. Elevated copeptin levels (>10 pmol/L) were found in 1174 patients (60.0%) in the entire cohort (58.1% in ACS and 68.5% in non-ACS, respectively) and mortality rates were significantly higher than in patients with normal copeptin levels (29.0% vs. 10.7%, p < 0.001). In a multivariate Cox regression, elevated copeptin was independently associated with all-cause death in the ACS (HR = 1.7, 1.3-2.3, p = 0.002) and non-ACS cohort (HR = 2.7, 1.4-5.0, p = 0.0018). CONCLUSION: Copeptin may aid in identifying patients at risk for adverse outcomes in patients with increased levels of hs-cTnT in ACS patients and in non-ACS conditions.

RAPID-CPU: a prospective study on implementation of the ESC 0/1-hour algorithm and safety of discharge after rule-out of myocardial infarction.

BACKGROUND: Although the value of fast diagnostic protocols in suspected acute coronary syndrome has been validated, there is insufficient real world evidence including patients with lower pre-test probability, atypical symptoms and confounding comorbidities. The feasibility, efficacy and safety of European Society of Cardiology (ESC) 0/1 and 0/3-hour algorithms using high-sensitivity troponin T were evaluated in a consecutive cohort with suspected acute coronary syndrome. METHODS: During 12 months, 2525 eligible patients were enrolled. In a pre-implementation period of 6 months, the prevalence of protocols, disposition, lengths of emergency department stay and treatments were registered. Implementation of the 0/1-hour protocol was monitored for another 6 months. Primary endpoints comprised the change of diagnostic protocols and 30-day mortality after direct discharge from the emergency department. RESULTS: Use of the ESC 0/1-hour algorithm increased by 270% at the cost of the standard 0/3-hour protocol. After rule-out (1588 patients), 1309 patients (76.1%) were discharged directly from the emergency department, with an all-cause mortality of 0.08% at 30 days (one death due to lung cancer). Median lengths of stay were 2.9 (1.9-3.8) and 3.2 (2.7-4.4) hours using a single high-sensitivity troponin T below the limit of detection (5 ng/L) at presentation and the ESC 0/1-hour algorithm, respectively, as compared to 5.3 (4.7-6.5) hours using the ESC 0/3-hour rule-out protocol (P<0.001). Discharge rates increased from 53.9% to 62.8% (P<0.001), without excessive use of diagnostic resources within 30 days. CONCLUSION: Implementation of the ESC 0/1-hour algorithm is feasible and safe, is associated with shorter emergency department stay than the ESC 0/3-hour protocol, and an increase in discharge rates. TRIAL REGISTRATION: ClinicalTrials.gov , Unique identifier: NCT03111862.

Management and outcomes of patients with unstable angina with undetectable, normal, or intermediate hsTnT levels.

BACKGROUND: Patients with unstable angina (UA) are regarded to be at low risk for future coronary events. Guidelines discourage routine coronary angiography and recommend early discharge after individualized risk stratification. The relative value of clinical risk indicators as compared to cardiac troponin (cTn) alone is unsettled in the era of high-sensitivity cardiac troponin (hsTn) assays. We aimed to investigate the clinical characteristics, therapies, and outcomes of UA patients with different hsTnT concentrations. METHODS: During 12 months, 2525 patients were enrolled. UA was defined as unstable symptoms and either undetectable (< 5 ng/L), normal (5-14 ng/L) or stable elevated hsTnT (15-51 ng/L). Follow-up for 1-year mortality was available in 98.7%. RESULTS: A total of 280 patients (11.1%) received a diagnosis of UA. Mortality rates at 12 months were 0%, 1.9% and 6.9% in presence of undetectable, normal and stable elevated hsTnT. Elevated hsTnT > 99th percentile but not unstable symptoms carried an independent 3.25-fold (1.78-5.93) higher risk for all-cause death after adjustment for other clinical risk indicators or the GRACE score. Utilization of guideline-recommended therapies was high albeit lower than for non-ST-elevation myocardial infarction (NSTEMI). Significantly fewer patients with UA received dual antiplatelet therapy (DAPT, odds ratio (OR) 0.51 [95% CI 0.44-0.59], P < 0.0001), coronary angiography (CA, OR 0.79, [95% CI 0.74-0.87], P < 0.0001), and percutaneous coronary intervention (PCI, OR 0.50, [95% CI 0.40-0.61], P < 0.0001), compared to NSTEMI. However, prevalence of significant obstructive coronary artery disease requiring PCI was 31.8%, even in patients with undetectable hsTnT, indicating the need for stress testing. CONCLUSIONS: The current dichotomization of patients into UA and NSTEMI is no longer appropriate. Additional risk stratification seems warranted including the presence and magnitude of hsTn concentration and additional risk indicators. Clinical Trials Identifier: NCT03111862.

Gender-specific reference values for high-sensitivity cardiac troponin T and I in well-phenotyped healthy individuals and validity of high-sensitivity assay designation.

OBJECTIVE: To determine gender-specific reference limits of high-sensitivity (hs) cardiac troponins (cTn) and validity of hs assay designation for both genders. METHODS: After screening with a questionnaire, 827 presumably healthy individuals were further selected based on clinical criteria (n = 740), clinical criteria plus cardiac imaging including stress magnetic resonance imaging or stress echocardiography (n = 726), and extended cardio-pulmonary parameters (n = 626). Blood samples were measured with hs-cTnT (Roche Diagnostics) on a cobas e602 analyzer as well as hs-cTnI (Abbott Diagnostics) on an ARCHITECTi2000SR. The impact of health definition, statistical methods, instrument selection and limit of detection (LoD) on overall and gender-specific 99th percentiles was assessed. RESULTS: Median age was 56 years (50.9% female) for the total study cohort. 99th percentiles for females and males ranged between 13.1 and 13.3 ng/L and 16.8-19.9 ng/L for hs-cTnT as well as 10.3-12.5 ng/L and 27.4-29.7 ng/L for hs-cTnI depending on health definition. Utilization of stricter health definition criteria reduced the difference of the gender-specific 99th percentiles between males and females for hs-cTnT to 3.7 ng/L (males 16.8 ng/L, females 13.1 ng/L), whereas the difference rather increased for hs-cTnI to 19.4 ng/L (males 29.7 ng/L, females 10.3 ng/L). Values > LoD could be measured in the majority of males and females using hs-TnT (81.4-83.3% and 96.5-96.9%, respectively). In contrast, values > LoD could not be observed in the majority of females using hs-cTnI (38.4-41.1%). CONCLUSIONS: In a well-phenotyped healthy cohort, reference values for hs-cTnT were slightly higher, whereas hs-cTnI cut-offs were considerably lower than previously observed. Gender differences were more pronounced in hs-cTnI than in hs-cTnT and were further reduced for hs-cTnT by application of stricter health definition criteria. Contrary to hs-cTnI, hs-cTnT fulfilled criteria for hs designation for both genders.

High-sensitivity cardiac troponin T as an independent predictor of stroke in patients admitted to an emergency department with atrial fibrillation.

AIMS: Elevated levels of high-sensitivity cardiac troponin T (hsTnT) are associated with adverse outcomes in numerous patient populations. Their value in prediction of stroke risk in patients with atrial fibrillation (AF) is in debate. METHODS: The study population included 2898 consecutive patients presenting with AF to the emergency department of the Department of Cardiology, Heidelberg University Hospital. Associations between hsTnT and stroke risk were assessed using multivariable Cox regression. RESULTS: Elevated hsTnT levels (>14 ng/L) were associated with increased risk of stroke. Even after adjustment for various risk factors, elevated hsTnT remained independently associated with stroke risk in patients with AF, adjusted hazard ratio 2.35 [95% confidence interval (CI): 1.26-4.36] (P = 0.007). These results were consistent across important subgroups (age, renal function, ejection fraction, CHA2DS2-VASc score and main admission diagnosis). For hsTnT, area under the receiver-operating-characteristic curve (AUC) was 0.659 [95% CI: 0.575-0.742], compared to 0.610 [95% CI: 0.526-0.694] for the CHA2DS2-VASc score. Inclusion of hsTnT in the multivariable model for stroke risk prediction consisting of all variables of the CHA2DS2-VASc score was associated with a significant improvement of its discriminatory power. CONCLUSION: Elevated hsTnT levels are significantly associated with higher risk of stroke and provide prognostic information independent of CHA2DS2-VASc score variables. Measurement of hsTnT may improve prediction of stroke risk in patients presenting to an emergency department with AF as compared to risk stratification based only on clinical variables.

Risk prediction in stable cardiovascular disease using a high-sensitivity cardiac troponin T single biomarker strategy compared to the ESC-SCORE.

Objective: To evaluate the prognostic performance of high-sensitivity cardiac troponin T (hs-cTnT) compared with the ESC-SCORE. Methods: We included low-risk outpatients with stable cardiovascular (CV) disease categorised into need for non-secondary and secondary prevention. The prognostication of hs-cTnT at index visit was compared with the European Society of Cardiology-Systematic COronary Risk Evaluation (ESC-SCORE) with respect to all-cause mortality (ACM) and two composite endpoints (ACM, acute myocardial infarction (AMI) and stroke and ACM, AMI, stroke and rehospitalisation for acute coronary syndrome (ACS) and decompensated heart failure (DHF)). Results: Within a median follow-up of 796 days, a total of 16 deaths, 32 composite endpoints of ACM, AMI and stroke and 83 composite endpoints of ACM, AMI, stroke, rehospitalisation for ACS and DHF were observed among 693 stable low-risk outpatients. Using C-statistics, measurement of hs-cTnT alone outperformed the ESC-SCORE for the prediction of ACM in the entire study population (Δarea under the curve (AUC) 0.221, p=0.0039) and both prevention groups (non-secondary: ΔAUC 0.164, p=0.0208; secondary: ΔAUC 0.264, p=0.0134). For the prediction of all other secondary endpoints, hs-cTnT was at least as effective as the ESC-SCORE, both in secondary and non-secondary prevention. Using continuous and categorical net reclassification improvement and integrated discrimination improvement, hs-cTnT significantly improved reclassification regarding all endpoints in the entire population and in the secondary prevention cohort. In non-secondary prevention, hs-cTnT improved reclassification only for ACM. The results were confirmed in an independent external cohort on 2046 patients. Conclusions: Hs-cTnT is superior to the multivariable ESC-SCORE for the prediction of ACM and a composite endpoint in stable outpatients with and without relevant CV disease. Trial registration number: NCT01954303; Pre-results.

Prognostic value of access and non-access sites bleeding after percutaneous coronary intervention.

BACKGROUND: Little is known about the impact of bleeding site on mortality after percutaneous coronary intervention. The aim of this study was to assess the impact of access and non-access site bleeding within 30 days after percutaneous coronary intervention on mortality. METHODS AND RESULTS: This study represents a pooled patient-level analysis of 14 180 patients recruited in 7 randomized trials. Access and non-access site bleeding were assessed using the Bleeding Academic Research Consortium criteria. The primary outcome was 1-year mortality. Follow-up was complete in 97.5% of the patients. There were 414 deaths within the first year after percutaneous coronary intervention: 44 deaths among patients with access site bleeding, 60 deaths among patients with non-access site bleeding, and 310 deaths among patients without bleeding (Kaplan-Meier estimates of mortality, 4.5%, 10.0%, and 2.5%, respectively; adjusted hazard ratio, 1.72 [95% confidence interval, 1.19-2.47] for access site bleeding versus no bleeding; hazard ratio, 2.78 [2.00-3.86] for non-access site versus no bleeding). The inclusion of non-access site bleeding (the absolute and relative integrated discrimination improvement, 0.005 and 8.9%; P=0.031) but not of access site bleeding (the absolute and relative integrated discrimination improvement, 0.0015 and 2.7%; P=0.084) was associated with an improvement of the discriminatory power of multivariable model for mortality prediction. CONCLUSIONS: Both access and non-access site bleeding events occurring within 30 days of a percutaneous coronary intervention are independently associated with an increased risk of 1-year mortality. Non-access site bleeding is a stronger correlate of mortality than access site bleeding, and it improves the discriminatory power of models for mortality prediction.