Large-scale WGS of carbapenem-resistant Acinetobacter baumannii isolates reveals patterns of dissemination of ST clades associated with antibiotic resistance.

OBJECTIVES: To describe the population genetics and antibiotic resistance gene distribution of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates causing infections in three Mediterranean countries. METHODS: Isolates were collected during the 2013-17 AIDA clinical trial in six hospitals in Israel, Greece and Italy. WGS, bioinformatic characterization and antibiotic resistance profiling were performed. RESULTS: In the 247 CRAB isolates characterized in this study, ST distribution varied by country: 29/31 (93.5%) Greek isolates, 34/41 (82.9%) Italian isolates and 70/175 (40.0%) Israeli isolates belonged to ST2. The identified ST2 isolates included eight distinct clades: 2C, 2D and 2H were significantly more common in Italy, while 2F was unique to Greece. The uncommon ST3 was not present among Greek isolates and constituted only 5/41 (12%) Italian isolates. On the other hand, it was much more common among Israeli isolates: 78/175 (44.6%) belonged to ST3. The vast majority of isolates, 240/247 (97.2%), were found to harbour acquired carbapenemases, primarily blaOXA-23. The chromosomal oxaAb (blaOXA-51-like) and ampC genes characteristic of this organism were also ubiquitous. Most (96.4%) ST3 isolates carried a broad-host-range plasmid IncP1α. CONCLUSIONS: The geographical differences in CRAB populations support the theory that clonal spread of CRAB leads to endemicity in hospitals and regions. The close association between antibiotic resistance genes and clades, and between plasmids and STs, suggest that de novo creation of MDR A. baumannii is rare. The clustering of antibiotic resistance genes and plasmids that is unique to each clade/ST, and nearly uniform within clades/STs, suggests that horizontal transmission is rare but crucial to the clade's/ST's success.

Excluded versus included patients in a randomized controlled trial of infections caused by carbapenem-resistant Gram-negative bacteria: relevance to external validity.

BACKGROUND: Population external validity is the extent to which an experimental study results can be generalized from a specific sample to a defined population. In order to apply the results of a study, we should be able to assess its population external validity. We performed an investigator-initiated randomized controlled trial (RCT) (AIDA study), which compared colistin-meropenem combination therapy to colistin monotherapy in the treatment of patients infected with carbapenem-resistant Gram-negative bacteria. In order to examine the study's population external validity and to substantiate the use of AIDA study results in clinical practice, we performed a concomitant observational trial. METHODS: The study was conducted between October 1st, 2013 and January 31st, 2017 (during the RCTs recruitment period) in Greece, Israel and Italy. Patients included in the observational arm of the study have fulfilled clinical and microbiological inclusion criteria but were excluded from the RCT due to receipt of colistin for > 96 h, refusal to participate, or prior inclusion in the RCT. Non-randomized cases were compared to randomized patients. The primary outcome was clinical failure at 14 days of infection onset. RESULTS: Analysis included 701 patients. Patients were infected mainly with Acinetobacter baumannii [78.2% (548/701)]. The most common reason for exclusion was refusal to participate [62% (183/295)]. Non-randomized and randomized patients were similar in most of the demographic and background parameters, though randomized patients showed minor differences towards a more severe infection. Combination therapy was less common in non-randomized patients [31.9% (53/166) vs. 51.2% (208/406), p = 0.000]. Randomized patients received longer treatment of colistin [13 days (IQR 10-16) vs. 8.5 days (IQR 0-15), p = 0.000]. Univariate analysis showed that non-randomized patients were more inclined to clinical failure on day 14 from infection onset [82% (242/295) vs. 75.5% (307/406), p = 0.042]. After adjusting for other variables, non-inclusion was not an independent risk factor for clinical failure at day 14. CONCLUSION: The similarity between the observational arm and RCT patients has strengthened our confidence in the population external validity of the AIDA trial. Adding an observational arm to intervention studies can help increase the population external validity and improve implementation of study results in clinical practice. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov, number NCT01732250 on November 22, 2012.

Predicting the risk of late futile outcome after transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) for aortic stenosis (AS) risk assessment is still developing and mostly concerned with mortality in the periprocedural period. We therefore sought to develop and then validate a score to predict 1-year adverse outcome. METHODS: Patients that underwent TAVI for severe AS in the Israeli registry. Patients with unsuccessful/suboptimal implantation were excluded. The cohort was split to derivation/validation cohorts by a ratio of 70:30. The outcome was defined as 1-year composite of mortality, stroke, and no improvement in NYHA class (vs. baseline). Logistic regression was used to fit the prediction model. RESULTS: Out of 2,440 patients meeting inclusion criteria, 276 were excluded, leaving 2,160 patients for both cohorts. At 1 year, 299 (14%) patients experienced the adverse ("futile") outcome. The derived prediction model included mean aortic valve (AV) gradient, previous pacemaker, previous oncological disease, need for diuretics, baseline NYHA class, hemoglobin and creatinine levels, and nonfemoral access site. The model's area under the curve (AUC) was 0.69 in the derivation and 0.70 in the validation cohort. Performance of other scores in the validation cohort were lower (0.60 for STS, 0.55 for Euroscore2, 0.56 for TVT score, and 0.53 for TAVI2-score, p = .03). Based on three risk tiers, patients had a low risk (20/306, 7% futility), a medium risk (50/304, 17%), and high risk (18/37, 49%) for futility. CONCLUSIONS: The TAVI futility risk model can be used to provide further insight regarding prediction measures and/or patients' outcomes outside of the periprocedural period (NCT02023060).

Immunosuppression reduction in liver and kidney transplant recipients with suspected bacterial infection: A multinational survey.

BACKGROUND: There is no consensus on the optimal management of immunosuppression during bacterial infections among solid organ transplant recipients. METHODS: A multicenter, cross-sectional survey, of high-volume kidney and liver transplant centers across US and Europe. Structured questionnaires including six multiple-choice questions concerning the management of immunosuppression during infection were distributed among 381 centers. RESULTS: A total of 124 (33%) centers fully completed the questionnaire: 67 liver, 57 kidney centers. Participating centers reported heterogenous approaches to immunosuppression management for all types of immunosuppressive drugs. Notably, kidney centers reported similar frequencies of either discontinuation (19%), continuation (19%), or dose reduction (17.5%) of antimetabolites; discontinuation only for life-threatening infection (17.5%) or case by case decisions (27%). Calcineurin inhibitors (CNI) management was heterogenous mostly among liver centers, with 8% discontinuing the CNI, 18% continuing, and 22% reducing dose. Heterogenous approaches to management of steroids and inhibitors of the mammalian target of rapamycin were also demonstrated. CONCLUSIONS: Immunosuppression management during bacterial infection is heterogenous in US and European centers. Immunosupression reduction (ISR) during infection is a common practice, though supported by limited evidence. Demonstrating high heterogeneity in the approach to ISR, together with the equivocal results of clinical studies, support consideration of an interventional clinical trial.

Management of Iron Deficiency in Heart Failure.

Anemia is a common finding in patients with heart failure (HF). The cause for anemia is multifactorial, with iron deficiency being the most common cause. Anemia with HF is an established predictor of morbidity and mortality. Iron deficiency in systolic HF, even without anemia, has been associated with increased mortality, increased hospitalizations, and decreased functional capacity and quality of life measures. Data from several randomized controlled trials and meta-analyses of iron deficiency and systolic HF show a beneficial effect for intravenous (IV) iron in terms of quality of life and functional capacity (improvements in 6-min walk test, and improvements in New York Heart Association functional class), as well as decreased hospitalizations for HF and reduction in cardiovascular mortality rates. Limited evidence exists for a beneficial effect of IV iron in diastolic dysfunction. Patients with symptomatic systolic HF should undergo an anemia diagnostic work-up. When iron deficiency (defined as ferritin <100 ng/mL or serum ferritin 100-299 ng/mL and transferrin saturation <20%) is present, current evidence supports treating HF patients with iron deficiency with IV iron.

Meta-analysis of Polymyxin Use in Patients.

In this chapter, we systematically reviewed studies that assessed polymyxin's effectiveness and summarized results through meta-analysis. The outcomes addressed were all-cause mortality, assuming that for patients with severe multidrug-resistant infections survival is the most important outcome, and resistance development, important for future patients. Most clinical data on polymyxins in the literature are from retrospective, observational studies at high risk of bias. The majority of clinical studies were unpowered to examine mortality controlling for other risk factors. The studies had no control of dosage regimens and treatment modifications. We identified several areas of missing data, in particular randomized controlled trials (RCTs) examining treatment options for carbapenem-resistant Gram-negative bacteria, different dosage regimens, polymyxins versus alternative antibiotics (e.g. aminoglycosides, tigecycline), and monotherapy versus specific combination therapies. Ideally, mortality and development of resistance should be examined in RCTs, with further longitudinal studies required for the latter.

Predicting the unpredictable mortality outcome of valve-in-valve interventions.

Surgical aortic valve replacement (AVR) risk scores overestimate valve-in-valve (ViV) transcatheter AVR (TAVR) mortality, with moderate discrimination Due to low prevalence of 30-day mortality, positive predictive value is low Specific risk score examining multiple outcomes for TAVR and ViV patients are needed.

Empirical Antibiotic Treatment Does Not Improve Outcomes in Catheter-Associated Urinary Tract Infection: Prospective Cohort Study.

BACKGROUND: Catheter associated urinary tract infection (CAUTI) is the most common healthcare-associated acquired infection. We aimed to describe the short- and long-term survival of patients with CAUTI and the impact of the empirical antibiotic treatment on survival rates. METHODS: In this prospective observational study we included consecutive adult patients with a chronic indwelling catheter-associated UTI and sepsis hospitalized in medical departments. The primary outcomes were 30-days all-cause mortality and long-term survival at end of the follow-up. A multivariate analysis using logistic regression and Cox proportional hazard model was performed to identify independent risk factors for an adverse outcome. A propensity-score model for receiving appropriate empirical antibiotic therapy was constructed and used to match patients. RESULTS: Overall, 315 consecutive patients with CAUTI were enrolled. The cohort consisted of elderly to very old patients (mean age 79.2 ± 11.5). The crude 30-day all-cause mortality rate was 30.8% (97/315). The median survival time was 82 days (interquartile range [IQR] 22-638). Appropriate early empirical treatment had no statistically significant association with 30-day mortality, propensity score-matched odds ratio (OR) 1.39 (0.76-2.55). Similarly, in the propensity-matched cohort, appropriate empirical treatment was not statistically associated with long-term survival (hazard ratio [HR] = 0.99, 95% confidence interval [CI] 0.75-1.3). CONCLUSIONS: In our setting, patients with CAUTI had poor short- and long-term prognosis regardless of appropriate empirical antibiotic treatment. Avoiding empirical antibiotics for CAUTI might be an important antibiotic stewardship intervention in hospitals.

Polymyxin monotherapy or in combination against carbapenem-resistant bacteria: systematic review and meta-analysis.

OBJECTIVES: The objective of this study was to summarize available data on polymyxin-based combination therapy or monotherapy for carbapenem-resistant Gram-negative bacteria. METHODS: This is a systematic review. We included observational studies and randomized controlled trials (RCTs) comparing polymyxin monotherapy versus polymyxin-based combination therapy in adult patients with infections caused by carbapenem-resistant or carbapenemase-producing Gram-negative bacteria. Only named antibiotic regimens were included. The primary outcome was 30 day mortality. Unadjusted OR (uOR) and adjusted OR where available with 95% CI were pooled in random-effects meta-analyses. RESULTS: Twenty-two studies including 28 comparisons were included. Polymyxin monotherapy was associated with a uOR of 1.58 (95% CI = 1.03-2.42) for mortality compared with polymyxin/carbapenem combination therapy (seven observational studies, 537 patients), without heterogeneity. Subgrouping studies to serious and critical risk of bias resulted in uORs of 0.94 (95% CI = 0.42-2.09) and 1.94 (95% CI = 1.17-3.23), respectively. Mortality was significantly higher with polymyxin monotherapy compared with combination therapy with tigecycline, aminoglycosides or fosfomycin (potentially double-coverage regimens): uOR of 1.57 (95% CI = 1.06-2.32) overall (10 observational studies and 1 RCT, 585 patients, no heterogeneity) and uOR of 2.09 (95% CI = 1.21-3.6) for Klebsiella pneumoniae bacteraemia (7 observational studies, 285 patients, no heterogeneity); very low quality evidence. Two RCTs and one observational study assessing rifampicin/colistin combination therapy for Acinetobacter baumannii infections showed no difference in mortality compared with colistin monotherapy; moderate quality evidence. CONCLUSIONS: The significant association observed in observational studies between polymyxin monotherapy and mortality cannot be taken as proof of combination therapy effects due to the low quality of the evidence. The only three RCTs to date show no effect of rifampicin/colistin or fosfomycin/colistin on mortality for Acinetobacter infections.

Trimethoprim/sulfamethoxazole versus vancomycin in the treatment of healthcare/ventilator-associated MRSA pneumonia: a case-control study.

Objectives: Therapeutic options available to treat MRSA pneumonia are limited. Trimethoprim/sulfamethoxazole is an attractive treatment because of its bactericidal anti-MRSA activity, oral and parenteral formulations and good penetration to the lung tissue. We aimed to compare the efficacy and safety of trimethoprim/sulfamethoxazole with vancomycin in the treatment of healthcare/ventilator-associated MRSA pneumonia. Methods: We carried out a retrospective case-control study of all consecutive hospitalized adult patients diagnosed with MRSA pneumonia at Beilinson Hospital during 2010-15 and treated with either vancomycin or trimethoprim/sulfamethoxazole. The primary outcomes were all-cause mortality at 30 days and clinical failure at the end of treatment. In order to reduce bias affecting the decision to use a specific antibiotic and as a sensitivity analysis, a propensity-score model for choosing between vancomycin and trimethoprim/sulfamethoxazole was used. Results: We identified 42 patients with MRSA pneumonia treated with trimethoprim/sulfamethoxazole and 39 treated with vancomycin. There were no significant differences in the baseline characteristics between the groups. Vancomycin-treated patients showed significantly higher 30 day mortality on both multivariate analysis (HR = 5.28; 95% CI = 1.50-18.60; P < 0.05) and sensitivity analysis with propensity score [vancomycin 13/24 (54.1%) versus trimethoprim/sulfamethoxazole 4/24 (16.7%); P < 0.05], and higher clinical failure rates [vancomycin 23/39 (59%) versus trimethoprim/sulfamethoxazole 15/42 (35.7%); P < 0.05], also in the sensitivity analysis with propensity score [vancomycin 14/24 (58.3%) versus trimethoprim/sulfamethoxazole 6/24 (25%); P < 0.05]. The rates of side effects in both arms were comparable. Conclusions: Trimethoprim/sulfamethoxazole appears to be superior to vancomycin in the treatment of MRSA pneumonia. A large-scale randomized controlled trial is needed to evaluate these findings.

The Effectiveness and Safety of High-Dose Colistin: Prospective Cohort Study.

BACKGROUND: Optimizing colistin dosing should translate to improved patient outcomes. METHODS: We used data from 2 prospective cohort studies performed between 2006 and 2009 and between 2012 and 2015. In the latter period, a new policy of high-dose colistin (9 million international units [MIU] loading dose followed by 9 MIU daily for normal renal function) was introduced in 2 participating hospitals. We included adult inpatients with invasive infections caused by carbapenem-resistant gram-negative bacteria treated with colistin. Our primary exposure variable was colistin dose, dichotomized to high-dose vs other regimens. The primary outcome was 28-day mortality. We generated a propensity score for high-dose colistin and conducted propensity-adjusted multivariable and matched-cohort analyses for mortality. RESULTS: Of 529 consecutive patients fulfilling inclusion criteria, 144 were treated with high-dose colistin and 385 with lower-dose colistin regimens. The median daily dose in the high-dose group was 9 MIU (interquartile range [IQR], 9-9) vs 4 MIU (IQR, 3-6) with other regimens. There were 50 of 144 (34.7%) deaths with high-dose colistin vs 165 of 385 (42.9%) with low-dose colistin (P = .1). The propensity-adjusted odds ratio (OR) for mortality was 1.07 (95% confidence interval [CI], .63-1.83) for high-dose colistin. Similar results were obtained when using the study period as the exposure variable, in the subgroup of bacteremic patients (n = 207) and in the propensity-matched cohort (OR, 1.11 [95% CI, .67-1.82]). Nephrotoxicity (RIFLE injury or higher; OR, 2.12 [95% CI, 1.29-3.48]; n = 396) and seizures were significantly more common with high-dose colistin. CONCLUSIONS: In a large cohort, we found no association between high colistin dosing and all-cause mortality. High dosing was associated with more nephrotoxicity.

Resting energy expenditure, calorie and protein consumption in critically ill patients: a retrospective cohort study.

BACKGROUND: Intense debate exists regarding the optimal energy and protein intake for intensive care unit (ICU) patients. However, most studies use predictive equations, demonstrated to be inaccurate to target energy intake. We sought to examine the outcome of a large cohort of ICU patients in relation to the percent of administered calories divided by resting energy expenditure (% AdCal/REE) obtained by indirect calorimetry (IC) and to protein intake. METHODS: Included patients were hospitalized from 2003 to 2015 at a 16-bed ICU at a university affiliated, tertiary care hospital, and had IC measurement to assess caloric targets. Data were drawn from a computerized system and included the % AdCal/REE and protein intake and other variables. A Cox proportional hazards model for 60-day mortality was used, with the % AdCal/REE modeled to accommodate non-linearity. Length of stay (LOS) and length of ventilation (LOV) were also assessed. RESULTS: A total of 1171 patients were included. The % AdCal/REE had a significant non-linear (p < 0.01) association with mortality after adjusting for other variables (p < 0.01). Increasing the percentage from zero to 70 % resulted in a hazard ratio (HR) of 0.98 (CI 0.97-0.99) pointing to reduced mortality, while increases above 70 % suggested an increase in mortality with a HR of 1.01 (CI 1.01-1.02). Increasing protein intake was also associated with decreased mortality (HR 0.99, CI 0.98-0.99, p = 0.02). An AdCal/REE >70 % was associated with an increased LOS and LOV. CONCLUSIONS: The findings of this study suggest that both underfeeding and overfeeding appear to be harmful to critically ill patients, such that achieving an Adcal/REE of 70 % had a survival advantage. A higher caloric intake may also be associated with harm in the form of increased LOS and LOV. The optimal way to define caloric goals therefore requires an exact estimate, which is ideally performed using indirect calorimetry. These findings may provide a basis for future randomized controlled trials comparing specific nutritional regimens based on indirect calorimetry measurements.

The effect of obligatory Padua prediction scoring in hospitalized medically ill patients: A retrospective cohort study.

BACKGROUND: Venous thromboembolism (VTE) is considered a preventable cause of mortality. The evidence for the benefit of VTE prophylaxis in acute medical patients is non-conclusive. Meta-analysis of RCTs failed to demonstrate reduction of all-cause mortality, while showing higher risk of bleeding. The Israeli Ministry of Health has instructed to assess all acute medical patients for the risk for VTE using the Padua Prediction Score, without mandating prophylaxis. AIM: To evaluate the effect of filling the Padua score on clinical outcomes and VTE prophylaxis rates. METHODS: Retrospective Study was performed in Israel during the years 2014-2017. The participants were divided to Padua compliance vs non-compliance group. Primary outcome: 30-day mortality. Secondary outcomes: 90-day incidence of VTE and suspected major bleeding. A propensity-weighted logistic multiple regression was performed. RESULTS: 18,890 patients were included in the study. The fulfillment of the Padua score was associated with an increased use of VTE prophylaxis, OR 1.66 (95% CI 1.49-1.84). However, there was no reduction of mortality or VTE events, OR 1.13 (95% CI 0.97-1.31) and OR 1.22 (95% CI 0.79-1.8) respectively. Hospitalizations related to hemoglobin decrease were not statistically different between the two groups. CONCLUSIONS: Padua score for the assessment of VTE risk in medical wards was associated with higher administration of pharmacological prophylaxis without reduction in VTE or mortality rate. Its usage should be reassessed as a performance measure.

Systematic review and meta-analysis of in vitro synergy of polymyxins and carbapenems.

Our objective was to examine the evidence of in vitro synergy of polymyxin-carbapenem combination therapy against Gram-negative bacteria (GNB). A systematic review and meta-analysis were performed. All studies examining in vitro interactions of antibiotic combinations consisting of any carbapenem with colistin or polymyxin B against any GNB were used. A broad search was conducted with no language, date, or publication status restrictions. Synergy rates, defined as a fractional inhibitory concentration index of ≤0.5 or a >2-log reduction in CFU, were pooled separately for time-kill, checkerboard, and Etest methods in a mixed-effect meta-analysis of rates. We examined whether the synergy rate depended on the testing method, type of antibiotic, bacteria, and resistance to carbapenems. Pooled rates with 95% confidence intervals (CI) are shown. Thirty-nine published studies and 15 conference proceeding were included, reporting on 246 different tests on 1,054 bacterial isolates. In time-kill studies, combination therapy showed synergy rates of 77% (95% CI, 64 to 87%) for Acinetobacter baumannii, 44% (95% CI, 30 to 59%) for Klebsiella pneumoniae, and 50% (95% CI, 30 to 69%) for Pseudomonas aeruginosa, with low antagonism rates for all. Doripenem showed high synergy rates for all three bacteria. For A. baumannii, meropenem was more synergistic than imipenem, whereas for P. aeruginosa the opposite was true. Checkerboard and Etest studies generally reported lower synergy rates than time-kill studies. The use of combination therapy led to less resistance development in vitro. The combination of a carbapenem with a polymyxin against GNB, especially A. baumannii, is supported in vitro by high synergy rates, with low antagonism and less resistance development. These findings should be examined in clinical studies.

Self-Reported Mental and Physical Measures in Adult Fontan Patients.

Introduction: The Fontan procedure is a palliative operation for patients with single functional ventricles, arising from a heterogeneous group of heart defects. There is a considerable gap in evidence regarding the self-reported physical and mental health of these patients surviving to adulthood. Methods and Results: We administered the PROMIS® Global Short Form (v 1.2) to Fontan patients during their scheduled clinic visits during 2017−2018. The raw PROMIS scores were subsequently converted to standardized T-scores, where the mean performance was 50 for the general population. We used Cronbach's alpha to assess reliability, with >0.8 considered good. A total of 42 patients were included. The median age was 30 (IQR: 24−34) years and 59% (95% CI: 43−74%) were female. The median time from birth to operation was 4.5 (IQR: 3−8) years, with 55% having an extracardiac Fontan. The questionnaire had good internal reliability with an alpha of 0.87. Seventy-one percent of respondents rated their overall health as "excellent" or "good". The mean T-score for physical health was 46.6, lower than the age-group mean (51.6, p < 0.001). The mean T-score for mental health was 53.3, higher than the age-group mean (48.5, p < 0.001). T-scores showed strong correlation with each other (r = 0.7) and weak correlation with age and time from procedure. There was no association of T-score with diagnosis or operation type. Conclusions: Adult Fontan patients report better mental health despite worse reporting physical health compared with the age group means. Patient-reported measures can provide clinically meaningful insights about the care of patients with complex congenital heart disease.

Outcome of patients with prior coronary bypass surgery admitted with an acute coronary syndrome.

BACKGROUND: Patients with prior coronary artery bypass graft surgery (CABG) are at increased risk for recurrent cardiovascular ischaemic events. Advances in management have improved prognosis of patients with acute coronary syndrome (ACS), yet it is not known whether similar trends exist in patients with prior CABG. AIM: Examine temporal trends in the prevalence, treatment and clinical outcomes of patients with prior CABG admitted with ACS. METHODS: Time-dependent analysis of patients with or without prior CABG admitted with an ACS who enrolled in the ACS Israeli Surveys between 2000 and 2016. Surveys were divided into early (2000-2008) and late (2010-2016) time periods. Outcomes included 30 days major adverse cardiac events (30d MACE) (death, myocardial infarction, stroke, unstable angina, stent thrombosis, urgent revascularisation) and 1-year mortality. RESULTS: Among 15 152 patients with ACS, 1506 (9.9%) had a prior CABG. Patients with prior CABG were older (69 vs 63 years), had more comorbidities and presented more with non-ST elevation-ACS (82% vs 51%). Between time periods, utilisation of antiplatelets, statins and percutaneous interventions significantly increased in both groups (p<0.001 for each). The rate of 30d MACE decreased in patients with (19.1%-12.4%, p=0.001) and without (17.4%-9.5%, p<0.001) prior CABG. However, 1-year mortality decreased only in patients without prior CABG (10.5% vs 7.4%, p<0.001) and remained unchanged in patients with prior CABG. Results were consistent after propensity matching. CONCLUSIONS: Despite an improvement in the management and prognosis of patients with ACS in the last decade, the rate of 1-year mortality of patients with prior CABG admitted with an ACS remained unchanged.

Meta-analysis of studies examining the external validity of the dual antiplatelet therapy score.

AIMS: The dual antiplatelet therapy (DAPT) score is meant to aid clinicians choose the DAPT duration but attempts to examine the external validity of the DAPT score and its decision tool have reported mostly disappointing results. Our aim was to perform a meta-analysis of all available data on the external validity of the DAPT score. METHODS AND RESULTS: We conducted a meta-analysis of studies that examined the external validity of the DAPT score/its decision tool. Seven studies (77 274 patients) were included. Follow-up ranged from 6 to 24 (median 18) months. Overall, high (≥2) DAPT score was associated with increased risk for myocardial infarction (MI)/stent thrombosis (ST) [odds ratio (OR) 1.54, 95% confidence interval (CI) 1.41-1.69; P < 0.01], and lower risk for bleeding (OR 0.84, 95% CI 0.73-0.97; P = 0.01). In the high DAPT score stratum, extended (12-24 months), as compared to standard (6-12 months) DAPT duration was associated with a reduction in the risk for MI/ST (OR 0.67, 95% CI 0.48-0.94; P = 0.02), and no difference in the risk for bleeding (OR 1.04, 95% CI 0.65-1.66; P = 0.88), while in the low DAPT score stratum, extended DAPT duration was associated with no difference in the risk for MI/ST (OR 1.04, 95% CI 0.76-1.43; P = 0.80), and an increased risk for bleeding (OR 1.58, 95% CI 1.15-2.15; P < 0.01). CONCLUSIONS: This first meta-analysis of studies examining the external validation of the DAPT score and its decision tool, our results suggest that the DAPT score is useful both for stratifying post-percutaneous coronary intervention patients into risk strata for future ischaemic and bleeding events as well aiding in choosing the optimal DAPT duration for the individual patient.

Validation of the DAPT score in real-world patients undergoing coronary stent implantation.

OBJECTIVES: To assess the external validity of the Dual Antiplatelet Therapy (DAPT) score decision tool in real world patients. METHODS AND RESULTS: Retrospective study using an all comers PCI registry. We compared the rates of myocardial infarction (MI) and actionable bleeding between 12 vs. 12+ months DAPT stratified by DAPT score category. Of 12,162 patients, 4471 (36.8%) completed a year of DAPT without events. The high DAPT score stratum patients were older and had a higher comorbidity burden. Overall, 12+ months DAPT duration was associated with reduced rates of MI (2.8% vs. 4.0%, p = 0.025) and similar rates of bleeding (2.6% vs. 1.9%, p = 0.281) compared to 12 months DAPT, but when stratified by DAPT score stratum, there was no difference in any of the outcomes in both high score group, (3.7% vs. 5.3%, p = 0.111 and 2.0% vs. 1.8%, p = 0.800, for MI and bleeding, respectively) and low score patients (2.7% vs. 3.1%, p = 0.656 and 2.8% vs. 2.0%, p = 0.308, for MI and bleeding, respectively). Overall clinical events (MI + bleeding) was again similar between patients treated with 12+ vs. 12 months DAPT (5.5% vs. 6.2%, p = 0.535 and 5.1% vs. 4.4%, p = 0.503 for high and low DAPT score, respectively). CONCLUSIONS: for real world patients completing 1 year of DAPT post PCI, rates of MI, actionable bleeding, and their combination did not differ between those treated with 12+ vs. 12 months DAPT stratified by DAPT score stratum. Clinicians should be aware of the DAPT score's limitations. Further studies examining the validity of the DAPT score in larger cohorts are required.