Elevated international normalised ratios correlate with severity of injury and outcome

Background. Haemorrhagic shock is the leading cause of preventable early deaths from trauma. Acute coagulopathy on admission to a trauma unit is associated with worse outcomes. The relationship of haemorrhage to early mortality remains consistent regardless of mechanism of injury. Haemorrhage and haemorrhagic shock are increasingly amenable to interventions that result in reductions in morbidity and mortality.Objectives. To assess the prevalence of coagulopathy in patients admitted to the level 1 trauma unit at Inkosi Albert Luthuli Central Hospital, Durban, South Africa, and correlate it with in-hospital mortality.Methods. A retrospective analysis of the first 1 000 patients admitted to the trauma unit during the years 2007 - 2011 was performed. The admission international normalised ratios (INRs) were correlated with Injury Severity Scores (ISSs) and in-hospital mortality. A multivariable Poisson model with robust standard errors was used to assess the relationship between coagulopathy and mortality after adjustment for the confounding influence of age and gender. The data were analysed using the R statistics program.Results. Of the 1 000 patients, 752 were male. There were 261 admissions directly from the scene and 739 inter-hospital transfers (nonscene). The mean INRs among survivors for all, scene and non-scene patients were 1.33, 1.30 and 1.34, respectively, and those among non-survivors 1.92, 2.01 and 1.88, respectively (p<0.001). The overall prevalence of coagulopathy was 48.7%, 46.9% in scene patients and 49.2% in non-scene patients. The mortality rate of scene patients with abnormal INR levels was 41.1% (adjusted relative risk (aRR) 3.59, 95% confidence interval (CI) 2.11 - 6.44; p<0.001) v. 25.1% for non-scene patients (aRR 1.67, 95% CI 1.15 - 2.05; p=0.004) (p=0.001).Conclusions. There was a high prevalence of coagulopathy in our study. Raised admission INRs were associated with worse outcomes. There was a direct correlation between the INR and the ISS. INRs may offer predictive capabilities in resource-depleted environments where the ISS is not routinely calculated. Early recognition of acute coagulopathy may help reduce morbidity and mortality

Direct admission versus inter-hospital transfer to a level I trauma unit improves survival An audit of the new Inkosi Albert Luthuli Central Hospital trauma unit

Objective. To audit the performance of a new level I trauma unit and trauma intensive care unit. Methods. Data on patients admitted to the level I trauma unit and trauma intensive care unit at Inkosi Albert Luthuli Central Hospital, Durban, from March 2007 to December 2008 were retrieved from the hospital informatics system and an independent database in the trauma unit. Results. Four hundred and seven patients were admitted; 71% of admissions were inter-hospital transfers (IHT) and 29% direct from scene (DIR). The median age was 27 years (range 1 - 83), and 71% were male. Blunt injury accounted for 66.3% of admissions and penetrating trauma for 33.7%. Of the former, motor vehicle-related injury accounted for 87.4%, with 81% of paediatric admissions due to pedestrian-related injuries. The median injury severity score (ISS) for the entire cohort was 22 (survivors 18, deaths 29; p<0.001). Patients in the DIR group had a significantly higher mean ISS compared with the IHT group (DIR 25, IHT 20; p<0.02). The overall mortality rate was 26.3%. There were 37 deaths (31.1%) in the DIR group and 70 (24.3%) in the IHT group (p=0.19). In patients surviving more than 12 hours the overall mortality rate was 21.1% (DIR 13.7%, IHT 23.5%; p=0.042). Conclusions. Trauma is a major cause of premature death in the young. Despite a significantly higher median ISS in direct admissions, there was no difference in mortality. Of those surviving more than 12 hours, patients admitted directly had a significant decrease in mortality. Dedicated trauma units improve outcome in the critically injured

Elevated international normalised ratios correlate with severity of injury and outcome

Background. Haemorrhagic shock is the leading cause of preventable early deaths from trauma. Acute coagulopathy on admission to a trauma unit is associated with worse outcomes. The relationship of haemorrhage to early mortality remains consistent regardless of mechanism of injury. Haemorrhage and haemorrhagic shock are increasingly amenable to interventions that result in reductions in morbidity and mortality.Objectives. To assess the prevalence of coagulopathy in patients admitted to the level 1 trauma unit at Inkosi Albert Luthuli Central Hospital, Durban, South Africa, and correlate it with in-hospital mortality.Methods. A retrospective analysis of the first 1 000 patients admitted to the trauma unit during the years 2007 - 2011 was performed. The admission international normalised ratios (INRs) were correlated with Injury Severity Scores (ISSs) and in-hospital mortality. A multivariable Poisson model with robust standard errors was used to assess the relationship between coagulopathy and mortality after adjustment for the confounding influence of age and gender. The data were analysed using the R statistics program.Results.Of the 1 000 patients, 752 were male. There were 261 admissions directly from the scene and 739 inter-hospital transfers (non scene). The mean INRs among survivors for all, scene and non-scene patients were 1.33, 1.30 and 1.34, respectively, and those among non-survivors 1.92, 2.01 and 1.88, respectively (p<0.001). The overall prevalence of coagulopathy was 48.7%, 46.9% in scene patients and 49.2% in non-scene patients. The mortality rate of scene patients with abnormal INR levels was 41.1% (adjusted relative risk (aRR) 3.59, 95% confidence interval (CI) 2.11 - 6.44; p<0.001) v. 25.1% for non-scene patients (aRR 1.67, 95% CI 1.15 - 2.05; p=0.004) (p=0.001).Conclusions. There was a high prevalence of coagulopathy in our study. Raised admission INRs were associated with worse outcomes. There was a direct correlation between the INR and the ISS. INRs may offer predictive capabilities in resource-depleted environments where the ISS is not routinely calculated. Early recognition of acute coagulopathy may help reduce morbidity and mortality

Direct admission versus inter-hospital transfer to a level I trauma unit improves survival: An audit of the new Inkosi Albert Luthuli Central Hospital trauma unit

Objective. To audit the performance of a new level I trauma unit and trauma intensive care unit. Methods. Data on patients admitted to the level I trauma unit and trauma intensive care unit at Inkosi Albert Luthuli Central Hospital, Durban, from March 2007 to December 2008 were retrieved from the hospital informatics system and an independent database in the trauma unit. Results. Four hundred and seven patients were admitted; 71% of admissions were inter-hospital transfers (IHT) and 29% direct from scene (DIR). The median age was 27 years (range 1 - 83), and 71% were male. Blunt injury accounted for 66.3% of admissions and penetrating trauma for 33.7%. Of the former, motor vehicle-related injury accounted for 87.4%, with 81% of paediatric admissions due to pedestrian-related injuries. The median injury severity score (ISS) for the entire cohort was 22 (survivors 18, deaths 29;

South African cardiovascular risk stratification guideline for non-cardiac surgery

The South African (SA) guidelines for cardiac patients for non-cardiac surgery were developed to address the need for cardiac risk assessment and risk stratification for elective non-cardiac surgical patients in SA, and more broadly in Africa. The guidelines were developed by updating the Canadian Cardiovascular Society Guidelines on Perioperative Cardiac Risk Assessment and Management for Patients Who Undergo Non-cardiac Surgery, with a search of literature from African countries and recent publications. The updated proposed guidelines were then evaluated in a Delphi consensus process by SA anaesthesia and vascular surgical experts. The recommendations in these guidelines are: 1. We suggest that elective non-cardiac surgical patients who are 45 years and older with either a history of coronary artery disease, congestive cardiac failure, stroke or transient ischaemic attack, or vascular surgical patients 18 years or older with peripheral vascular disease require further preoperative risk stratification as their predicted 30-day major adverse cardiac event (MACE) risk exceeds 5% (conditional recommendation: moderate-quality evidence). 2. We do not recommend routine non-invasive testing for cardiovascular risk stratification prior to elective non-cardiac surgery in adults (strong recommendation: low-to-moderate-quality evidence). 3. We recommend that elective non-cardiac surgical patients who are 45 years and older with a history of coronary artery disease, or stroke or transient ischaemic attack, or congestive cardiac failure or vascular surgical patients 18 years or older with peripheral vascular disease should have preoperative natriuretic peptide (NP) screening (strong recommendation: high-quality evidence). 4. We recommend daily postoperative troponin measurements for 48 - 72 hours for non-cardiac surgical patients who are 45 years and older with a history of coronary artery disease, or stroke or transient ischaemic attack, or congestive cardiac failure or vascular surgical patients 18 years or older with peripheral vascular disease, i.e. (i) a baseline risk >5% for MACE 30 days after elective surgery (if no preoperative NP screening), or (ii) an elevated B-type natriuretic peptide (BNP)/N-terminal-prohormone B-type natriuretic peptide (NT-proBNP) measurement before elective surgery (defined as BNP >99 pg/mL or a NT-proBNP >300 pg/mL) (conditional recommendation: moderate-quality evidence). Additional recommendations are given for the management of myocardial injury after non-cardiac surgery (MINS) and medications for comorbidities.The Global Surgery Fellowship grant.http://www.samj.org.zadm2022Anaesthesiolog

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p