Inotrope versus placebo therapy in cardiogenic shock: Rationale and study design of the CAPITAL DOREMI2 trial.

BACKGROUND: Cardiogenic shock (CS) is a state of end-organ hypoperfusion related to cardiac dysfunction. Current guidelines recommend consideration of inotrope therapy in patients with CS, however no robust data support their use. The purpose of the CAPITAL DOREMI2 trial is to examine the efficacy and safety of inotrope therapy against placebo in the initial resuscitation of patients with CS. METHODS AND DESIGN: This is a multi-center, double-blind, randomized, placebo-controlled trial comparing single-agent inotrope therapy to placebo in patients with CS. A total of 346 participants with Society for Cardiovascular Angiography and Interventions class C or D CS will be randomized in a 1:1 fashion to inotrope or placebo therapy, which will be administered over a 12-hour period. After this period, participants will continue open-label therapies at the discretion of the treating team. The primary outcome is a composite of all-cause in-hospital death, and, as measured during the 12-hour intervention period, any of: sustained hypotension or high dose vasopressor requirements, lactate greater than 3.5 mmol/L at 6 hours or thereafter, need for mechanical circulatory support, arrhythmia leading to emergent electrical cardioversion, and resuscitated cardiac arrest. All participants will be followed for the duration of their hospitalization, and secondary outcomes will be assessed at the time of discharge. IMPLICATION: This trial will be the first to establish the safety and efficacy of inotrope therapy against placebo in a population of patients with CS and has the potential to alter the standard care provided to this group of patients.

Evolving outcomes of extracorporeal membrane oxygenation during the first 2 years of the COVID-19 pandemic: a systematic review and meta-analysis.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been used extensively for coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS). Reports early in the pandemic suggested that mortality in patients with COVID-19 receiving ECMO was comparable to non-COVID-19-related ARDS. However, subsequent reports suggested that mortality appeared to be increasing over time. Therefore, we conducted an updated systematic review and meta-analysis, to characterise changes in mortality over time and elucidate risk factors for poor outcomes. METHODS: We conducted a meta-analysis (CRD42021271202), searching MEDLINE, Embase, Cochrane, and Scopus databases, from 1 December 2019 to 26 January 2022, for studies reporting on mortality among adults with COVID-19 receiving ECMO. We also captured hospital and intensive care unit lengths of stay, duration of mechanical ventilation and ECMO, as well as complications of ECMO. We conducted random-effects meta-analyses, assessed risk of bias of included studies using the Joanna Briggs Institute checklist and evaluated certainty of pooled estimates using GRADE methodology. RESULTS: Of 4522 citations, we included 52 studies comprising 18,211 patients in the meta-analysis. The pooled mortality rate among patients with COVID-19 requiring ECMO was 48.8% (95% confidence interval 44.8-52.9%, high certainty). Mortality was higher among studies which enrolled patients later in the pandemic as opposed to earlier (1st half 2020: 41.2%, 2nd half 2020: 46.4%, 1st half 2021: 62.0%, 2nd half 2021: 46.5%, interaction p value = 0.0014). Predictors of increased mortality included age, the time of final patient enrolment from 1 January 2020, and the proportion of patients receiving corticosteroids, and reduced duration of ECMO run. CONCLUSIONS: The mortality rate for patients receiving ECMO for COVID-19-related ARDS has increased as the pandemic has progressed. The reasons for this are likely multifactorial; however, as outcomes for these patients evolve, the decision to initiate ECMO should include the best contextual estimate of mortality at the time of ECMO initiation.

Pulmonary artery catheterization in patients with cardiogenic shock: a systematic review and meta-analysis.

PURPOSE: Cardiogenic shock carries high morbidity and mortality. The purpose of this review was to determine the safety and efficacy of pulmonary artery catheterization (PAC) in adult patients hospitalized with cardiogenic shock. SOURCE: We performed a systematic review and meta-analysis of observational studies and randomized controlled trials comparing PAC vs no PAC in cardiogenic shock. We searched MEDLINE, EMBASE, Cochrane CENTRAL, and grey literature. We screened articles, abstracted data, and evaluated risk of bias in duplicate. We pooled data using a random-effects model and evaluated the quality of evidence using the GRADE framework. Outcomes of interest were mortality, length of stay, and procedural complications. PRINCIPAL FINDINGS: We identified 19 eligible observational studies (≥ 2,716,287 patients) and no randomized controlled trials; 14 studies were at high risk of bias (lack of adjustment for prognostic variables and/or co-interventions). When pooling adjusted results, PAC was associated with improved survival to hospital discharge (relative risk [RR], 0.77; 95% confidence interval [CI], 0.64 to 0.91, I2 = 98%; very low-quality evidence) and at longest available follow-up (RR, 0.72; 95% CI, 0.60 to 0.87; I2 = 99%; very low-quality evidence). Unadjusted length of stay was 3.5 days longer (95% CI, 1.49 to 5.54; I2 = 100%; very low-quality evidence) with PAC. Procedural complications were inconsistently reported. CONCLUSIONS: Very low-quality observational evidence suggests PAC use in patients with cardiogenic shock is associated with lower mortality. Overall, these results support consideration of PAC for hemodynamic assessment in cardiogenic shock. Prospective randomized clinical trials are needed to further characterize the role of PAC in this population.

RéSUMé: OBJECTIF: Le choc cardiogénique entraîne une morbidité et une mortalité élevées. Le but de cette revue était de déterminer la sécurité et l'efficacité de l'utilisation d'un cathétérisme de l'artère pulmonaire (CAP) chez des patients adultes hospitalisés en choc cardiogénique. SOURCES: Nous avons réalisé une revue systématique et une méta-analyse d'études observationnelles et d'études randomisées contrôlées comparant l'utilisation vs la non-utilisation de CAP pour le traitement d'un choc cardiogénique. Nous avons effectué des recherches dans les bases de données MEDLINE, EMBASE, Cochrane CENTRAL et dans la littérature grise. Nous avons examiné les articles, résumé les données et évalué le risque de biais à deux reprises. Nous avons regroupé les données à l'aide d'un modèle à effets aléatoires et évalué la qualité des données probantes en nous appuyant sur le système GRADE. Les issues d'intérêt étaient la mortalité, la durée de séjour et les complications procédurales. CONSTATATIONS PRINCIPALES: Nous avons identifié 19 études observationnelles admissibles (≥ 2 716 287 patients) et aucune étude randomisée contrôlée; 14 études comportaient un risque élevé de biais (absence d'ajustement sur les variables pronostiques et/ou les interventions concomitantes). En regroupant les résultats ajustés, le CAP a été associé à une meilleure survie jusqu'au congé de l'hôpital (risque relatif [RR], 0,77; intervalle de confiance [IC] à 95 %, 0,64 à 0,91, I2 = 98 %; données probantes de très faible qualité) et jusqu'au point de suivi disponible rapporté le plus lointain dans le temps (RR, 0,72; IC 95 %, 0,60 à 0,87; I2 = 99 %; données probantes de très faible qualité). La durée de séjour non ajustée était 3,5 jours plus longue (IC 95 %, 1,49 à 5,54; I2 = 100 %; données probantes de très faible qualité) avec un CAP. Les complications procédurales n'étaient par rapportées de manière uniforme. CONCLUSION: Des données observationnelles de très faible qualité suggèrent que l'utilisation d'un CAP chez des patients en choc cardiogénique est associée à une réduction de la mortalité. Dans l'ensemble, ces résultats suggèrent de considérer le CAP pour l'évaluation hémodynamique en cas de choc cardiogénique. Des études cliniques randomisées prospectives sont nécessaires pour mieux caractériser le rôle du CAP dans cette population.

Association of a Heart Failure Management Incentive in Primary Care With Clinical Outcomes: A Retrospective Cohort Study.

BACKGROUND: We aim to examine the association between primary care physicians' billing of Q050A, a pay-for-performance heart failure (HF) management incentive fee code, and the composite outcome of mortality, hospitalization, and emergency department visits. METHODS AND RESULTS: This population-based cohort study linked administrative health databases in Ontario, Canada, for patients with HF aged >66 years between January 1, 2008, and March 31, 2020. Cases were patients with HF who had a Q050A fee code billed. Cases and controls were matched 1:1 on age, sex, patient status on being rostered to a primary care physician, cardiologist, or internist visit in the 6 months before study enrollment, Johns Hopkins Adjusted Clinical Group resource use bands, days between HF diagnosis and study enrollment (±2 years), and the logit of the propensity score. A Cox proportional hazards model assessed the association of Q050A with the outcome. A total of 59 664 cases had a Q050A billed, whereas 244 883 patients did not. Before matching, patients who had a Q050A billed were more likely to be men (52% versus 49%), were rostered to a primary care physician (100% versus 96%), had a higher Charlson Comorbidity Index, and had higher health care costs. The mean follow-up was 481 days for cases and 530 days for controls. The composite outcome (hazard ratio, 1.11 [95% CI, 1.09-1.12]) was significantly higher for cases than controls. CONCLUSIONS: The Q050A incentive improved financial compensation for primary care physicians managing patients with HF but was not associated with improvements in the outcome. Research on promoting evidence-based HF management is warranted.

Factors Impacting Physician Prognostic Accuracy in Heart Failure Patients With Reduced Left Ventricular Ejection Fraction.

BACKGROUND: A recent study showed that the accuracy of heart failure (HF) cardiologists and family doctors to predict mortality in outpatients with HF proved suboptimal, performing less well than models. OBJECTIVES: The authors sought to evaluate patient and physician factors associated with physician accuracy. METHODS: The authors included outpatients with HF from 11 HF clinics. Family doctors and HF cardiologists estimated patient 1-year mortality. They calculated predicted mortality using the Seattle HF Model and followed patients for 1 year to record mortality (or urgent heart transplant or ventricular assist device implant as mortality-equivalent events). Using multivariable logistic regression, the authors evaluated associations among physician experience and confidence in estimates, duration of patient-physician relationship, patient-physician sex concordance, patient race, and predicted risk, with concordant results between physician and model predictions. RESULTS: Among 1,643 patients, 1-year event rate was 10% (95% CI: 8%-12%). One-half of the estimates showed discrepant results between model and physician predictions, mainly owing to physician risk overestimation. Discrepancies were more frequent with increasing patient risk from 38% in low-risk to ∼75% in high-risk patients. When making predictions on male patients, female HF cardiologists were 26% more likely to have discrepant predictions (OR: 0.74; 95% CI: 0.58-0.94). HF cardiologist estimates in Black patients were 33% more likely to be discrepant (OR: 0.67; 95% CI: 0.45-0.99). Low confidence in predictions was associated with discrepancy. Analyses restricted to high-confidence estimates showed inferior calibration to the model, with risk overestimation across risk groups. CONCLUSIONS: Discrepant physician and model predictions were more frequent in cases with perceived increased risk. Model predictions outperform physicians even when they are confident in their predictions. (Predicted Prognosis in Heart Failure [INTUITION]; NCT04009798).

Tracheostomy in Critically Ill COVID-19 Patients on Extracorporeal Membrane Oxygenation: A Single-Center Experience.

OBJECTIVES: Novel coronavirus-19 (COVID-19) has led to over 6 million fatalities globally. An estimated 75% of COVID-19 patients who require critical care admission develop acute respiratory distress syndrome (ARDS) needing invasive mechanical ventilation (IMV) and/or extracorporeal membrane oxygenation (ECMO). Due to prolonged ventilation requirements, these patients often also require tracheostomy. We performed a review of clinical outcomes in COVID-19 patients on ECMO at a high-volume tertiary care center in Hamilton, Ontario, Canada. METHODOLOGY: We performed a retrospective case series, including 24 adult patients diagnosed with COVID-19 who required IMV, veno-venous (ECMO), and tracheostomy. All patients were included from April to December 2021. We extracted demographic and clinical variables pertaining to the tracheostomy procedure and ECMO therapy. We performed descriptive statistical analyses. This study was approved by the Hamilton Integrated Research Ethics Board (14217-C). RESULTS: We included 24 consecutive patients with COVID-19 who required tracheostomy while undergoing ECMO therapy. The mean age was 49.4 years [standard deviation (SD): 7.33], the majority of patients were male (75%), with mean body mass index of 32 (SD: 8.81). Overall mortality rate was 33.3%. Percutaneous tracheostomy was performed most frequently (83.3%) and, similar to open tracheostomy, was associated with a low rate of perioperative bleeding complications. Within surviving patients, the mean time to IMV weaning and decannulation was 60.2 (SD: 24.6) and 49.4 days (SD: 21.8), respectively. CONCLUSION: Percutaneous tracheostomy appears to be safe in COVID-19 patients on ECMO and holding anticoagulation 24 hours prior to and after tracheostomy may limit bleeding events in these patients.

Intracranial hemorrhage in patients treated for SARS-CoV-2 with extracorporeal membrane oxygenation: A systematic review and meta-analysis.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is routinely used in patients with severe respiratory failure and has been increasingly needed during the COVID-19 pandemic. In patients treated with ECMO, significant intracranial hemorrhage (ICH) risk exists due to circuit characteristics, anticoagulation, and disease characteristics. ICH risk may be substantially higher in COVID-19 patients than patients treated with ECMO for other indications. METHODS: We systematically reviewed current literature regarding ICH during ECMO treatment of COVID-19. We utilized Embase, MEDLINE, and Cochrane Library databases. Meta-analysis was performed for included comparative studies. Quality assessment was performed using MINORS criteria. RESULTS: A total of 54 studies with 4000 ECMO patients were included, all retrospective. Risk of bias was increased via MINORS score primarily due to retrospective designs. ICH was more likely in COVID-19 patients (RR 1.72, 95% CI 1.23, 2.42). Mortality among COVID patients on ECMO with ICH was 64.0%, compared with 41% in patients without ICH (RR1.9, 95% 1.44, 2.51). CONCLUSION: This study suggests increased hemorrhage rates in COVID-19 patients on ECMO compared to similar controls. Hemorrhage reduction strategies may include atypical anticoagulants, conservative anticoagulation strategies, or biotechnology advances in circuit design and surface coatings.

Early Versus Delayed Coronary Angiography After Out-of-Hospital Cardiac Arrest Without ST-Segment Elevation-A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The optimal timing of coronary angiography remains unclear following out-of-hospital cardiac arrest (OHCA) without ST elevation on electrocardiogram. The objective of this systematic review and meta-analysis was to evaluate the efficacy and safety of early angiography versus delayed angiography following OHCA without ST elevation. DATA SOURCES: The databases MEDLINE, PubMed EMBASE, and CINHAL, as well as unpublished sources from inception to March 9, 2022. STUDY SELECTION: A systematic search was performed for randomized controlled trials of adult patients after OHCA without ST elevation who were randomized to early as compared to delayed angiography. DATA EXTRACTION: Reviewers screened and abstracted data independently and in duplicate. The certainty of evidence was assessed for each outcome using the Grading Recommendations Assessment, Development and Evaluation approach. The protocol was preregistered (CRD 42021292228). DATA SYNTHESIS: Six trials were included (n = 1,590 patients). Early angiography probably has no effect on mortality (relative risk [RR] 1.04; 95% CI 0.94-1.15; moderate certainty) and may have no effect on survival with good neurologic outcome (RR 0.97; 95% CI 0.87-1.07; low certainty) or ICU length of stay (LOS) (mean difference 0.41 days fewer; 95% CI -1.3 to 0.5 d; low certainty). Early angiography has an uncertain effect on adverse events. CONCLUSIONS: In OHCA patients without ST elevation, early angiography probably has no effect on mortality and may have no effect on survival with good neurologic outcome and ICU LOS. Early angiography has an uncertain effect on adverse events.

Cardiogenic shock in the context of newly diagnosed anomalous origin of the right coronary artery originating from the pulmonary artery: a case report.

BACKGROUND: Anomalous right coronary artery (RCA) from the pulmonary artery (ARCAPA) is a rare congenital heart abnormality with varying clinical presentations, for which multiple imaging modalities are often required for diagnosis. CASE SUMMARY: We present a case of a 76-year-old female presenting with 2 weeks of palpitations and shortness of breath who was found to be in rapid atrial fibrillation (AF) with congestive heart failure. Despite initial medical management, the patient developed cardiogenic shock with anuric renal failure. Emergent right and left heart catheterization did not demonstrate any significant obstructive coronary artery disease but showed severe right ventricular (RV) failure and raised the possibility of an ARCAPA. This diagnosis was further corroborated by findings on a subsequent transoesophageal echocardiogram. In view of profound decline and limited anticipated improvement, the patient ultimately decided to pursue comfort measures in a hospice setting. DISCUSSION: We postulate that the underlying aetiology of our patient's shock state was multifactorial, notably progressive RCA-territory ischaemia and RV failure, sepsis, and new-onset uncontrolled AF. In adults, unrecognized congenital heart disease can uncommonly cause cardiogenic shock. In our case, echocardiography and invasive angiography were integrated for the diagnosis of ARCAPA given the clinical circumstances that limited the use of cardiac computed tomography angiography.

Predicting Survival After VA-ECMO for Refractory Cardiogenic Shock: Validating the SAVE Score.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used increasingly to support patients who are in cardiogenic shock. Due to the risk of complications, prediction models may aid in identifying patients who would benefit most from VA-ECMO. One such model is the Survival After Veno-Arterial Extracorporeal Membrane Oxygenation (SAVE) score. Therefore, we wanted to validate the utility of the SAVE score in a contemporary cohort of adult patients. METHODS: Retrospective data were extracted from electronic health records of 120 patients with cardiogenic shock supported with VA-ECMO between 2011 and 2018. The SAVE score was calculated for each patient to predict survival to hospital discharge. We assessed the SAVE score calibration by comparing predicted vs observed survival at discharge. We assessed discrimination with the area under the receiver operating curve using logistic regression. RESULTS: A total of 45% of patients survived to hospital discharge. Survivors had a significantly higher mean SAVE score (-9.3 ± 4.1 in survivors vs -13.1 ± 4.4, respectively; P = 0.001). SAVE score discrimination was adequate (c = 0.77; 95% confidence interval 0.69-0.86; P < 0.001). SAVE score calibration was limited, as observed survival rates for risk classes II-V were higher in our cohort (II: 67% vs 58%; III: 78% vs 42%; IV: 61% vs 30%; and V: 29% vs 18%). CONCLUSIONS: The SAVE score underestimates survival in a contemporary North American cohort of adult patients with cardiogenic shock. Its inaccurate performance could lead to denying ECMO support to patients deemed to be too high risk. Further studies are needed to validate additional predictive models for patients requiring VA-ECMO.

CONTEXTE: L'oxygénation extracorporelle veino-artérielle (ECMO-VA) est de plus en plus utilisée comme assistance pour les patients qui sont en choc cardiogène. En raison du risque de complications, des modèles de prédiction peuvent aider à déterminer quels patients bénéficieraient le plus d'une ECMO-VA. Le score SAVE (Survival After Veno-Arterial Extracorporeal Membrane Oxygenation) est un modèle de ce genre. Par conséquent, nous voulions valider l'utilité du score SAVE dans une cohorte contemporaine de patients adultes. MÉTHODOLOGIE: Des données rétrospectives ont été extraites de dossiers médicaux électroniques de 120 patients atteints d'un choc cardiogène ayant reçu une ECMO-VA entre 2011 et 2018. Le score SAVE a été calculé pour chaque patient afin de prédire la survie au congé de l'hôpital. Nous avons évalué la calibration du score SAVE en comparant la survie prédite au moment du congé et la survie observée. Nous avons évalué la discrimination par l'aire sous la courbe opérationnelle chez le receveur en faisant appel à la régression logistique. RÉSULTATS: Au total, 45 % des patients ont survécu au congé de l'hôpital. Les survivants affichaient un score SAVE moyen considérablement plus élevé (­9,3 ± 4,1 chez les survivants vs ­13,1 ± 4,4; p = 0,001). La discrimination par le score SAVE était adéquate (c = 0,77; intervalle de confiance à 95 % : 0,69 à 0,86; p < 0,001). La calibration du score SAVE était limitée, car les taux pour les classes de risque II à V étaient plus élevés dans notre cohorte (II : 67 % vs 58 %; III : 78 % vs 42 %; IV : 61 % vs 30 %; et V : 29 % vs 18 %). CONCLUSIONS: Le score SAVE sous-estime la survie dans une cohorte nord-américaine contemporaine de patients adultes atteints d'un choc cardiogène. L'inexactitude de ses résultats pourrait faire en sorte qu'une assistance par ECMO serait refusée à des patients jugés comme présentant un risque élevé. D'autres études sont nécessaires pour valider d'autres modèles de prédiction pour les patients ayant besoin d'une ECMO-VA.

The Effect of Age on Outcomes After Destination-Therapy Left Ventricular Assist Device Implantation: An Analysis of the IMACS Registry.

BACKGROUND: As patients with advanced heart failure are living longer, defining the impact of left ventricular assist devices (LVADs) on outcomes in an aging population is of great importance. We describe overall survival, rates of adverse events (AEs), and post-AE survival in patients age ≥ 70 years vs age 50-69 years after destination-therapy (DT) LVAD implantation. METHODS: A retrospective analysis was conducted with the use of the International Society for Heart and Lung Transplantation Mechanically Assisted Circulatory Support (IMACS) registry. All adults age ≥ 50 years with a continuous-flow DT LVAD from 2013 to 2017 were included. The primary outcome was all-cause mortality. The secondary outcomes were the incidence of and survival after gastrointestinal (GI) bleeding, infection, stroke, pump thrombosis, pump exchange, and right-side heart failure. Mortality and AEs were assessed with the use of competing risk models. RESULTS: At total of 5,572 patients were included: 3,700 aged 50-69 and 1,872 aged ≥ 70. All-cause mortality by 42 months was 55.8% in patients aged ≥ 70 and 44.8% in patients aged 50-69 (P = 0.001). Patients aged ≥ 70 had a 37.8% higher risk of death after DT LVAD implantation (hazard ratio 1.378, 95% CI 1.251-1.517). Patients aged ≥ 70 had higher risk of GI bleeding but lower risk of right-side heart failure. There was no difference between age groups for risk of infection or stroke. Experiencing any AE was associated with an increased risk of death that did not vary with age. CONCLUSIONS: Patients aged ≥ 70 years have reduced survival after DT LVAD, in part because of increased GI bleeding, while the incidence of other AEs is similar to that of patients aged 50-69 years. Careful patient selection beyond age alone may allow for optimal outcomes after DT LVAD implantation.

Suicide Attempt by Self-Dissection of Permanent Pacemaker Leads.

We present the case of a patient with depression who attempted suicide through self-dissection and severing of her permanent pacemaker leads. The case highlights the importance of screening for psychiatric disorders prior to device implantation and continued surveillance for self-harm behaviors. (Level of Difficulty: Beginner.).

Epidemiology and risk factors for bloodstream infections in a home parenteral nutrition program.

BACKGROUND: An increasing number of patients with intestinal failure are receiving home parenteral nutrition (HPN). Associated complications include bloodstream infections (BSIs), but data on rates and risk factors for HPN-related BSIs are scarce. METHODS: A retrospective review was conducted of patients enrolled in the regional HPN program between 2001 and 2008. Demographic information and data on indication for HPN, duration of PN therapy, type and date of insertion of central venous access device, and blood culture results were recorded. RESULTS: In total, 155 patients (165 courses of HPN) were included for a total of 45,876 catheter days. The mean patient age was 49 years, and 105 (64%) patients were female. A total of 105 organisms were cultured from 93 distinct episodes of BSIs. The rate of BSI was found to be 2.0 per 1000 catheter days, but excluding BSIs with a single positive culture of coagulase-negative staphylococcus and diphtheroid bacilli, the rate of infection was 1.4 per 1000 catheter days. Male sex and underlying malignancy were significant predictors of BSI, with hazard ratios of 1.69 (95% confidence interval [CI], 1.14-2.60; P = .009) and 2.38 (95% CI, 1.53-3.50; P < .001). CONCLUSION: In a large heterogeneous group of HPN patients, the BSI rate ranged between 1.4 and 2.0 infections per 1000 catheter days. Isolated organisms were similar to those found in hospitalized patients. Male sex and underlying malignancy were significant risk factors for BSI. These high-risk patients are likely to benefit from interventions aimed at reducing BSIs.

Bleeding complications in patients with acute coronary syndromes: are they important and how can we prevent them?

Progress in antithrombotic medications and revascularization procedures has helped to reduce mortality in patients with acute coronary syndromes (ACS). However, these therapies can significantly increase the risk of bleeding. Bleeding complications are important clinical outcomes in patients with ACS. Data from numerous randomized controlled trials and large registries have demonstrated that bleeding is independently associated with a significantly higher risk of mortality in patients with ACS. Furthermore, bleeding complications are associated with an increased risk of recurrent ischemic events. The challenge of preventing bleeding complications while obtaining the optimal antithrombotic benefits of ACS management requires careful consideration of factors associated with patients, pharmacotherapy, and interventional procedures. Clinicians should be able to risk stratify patients for bleeding events just as they would do for recurrent ischemic events in ACS.

Bisphosphonate associated osteonecrosis of the jaw.

In 2003, the first reports describing osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BP) were published. These cases occurred in patients with cancer receiving high-dose intravenous BP; however, 5% of the cases were in patients with osteoporosis receiving low-dose bisphosphonate therapy. We present the results of a systematic review of the incidence, risk factors, diagnosis, prevention, and treatment of BP associated ONJ. We conducted a comprehensive literature search for relevant studies on BP associated ONJ in oncology and osteoporosis patients published before February 2008.All selected relevant articles were sorted by area of focus. Data for each area were abstracted by 2 independent reviewers. The results showed that the diagnosis is made clinically. Prospective data evaluating the incidence and etiologic factors are very limited. In oncology patients receiving high-dose intravenous BP, ONJ appears to be dependent on the dose and duration of therapy, with an estimated incidence of 1%-12% at 36 months of exposure. In osteoporosis patients, it is rare, with an estimated incidence < 1 case per 100,000 person-years of exposure. The incidence of ONJ in the general population is not known. Currently, there is insufficient evidence to confirm a causal link between low-dose BP use in the osteoporosis patient population and ONJ. We concluded BP associated ONJ is associated with high-dose BP therapy primarily in the oncology patient population. Prevention and treatment strategies are currently based on expert opinion and focus on maintaining good oral hygiene and conservative surgical intervention.

Canadian consensus practice guidelines for bisphosphonate associated osteonecrosis of the jaw.

OBJECTIVE: Following publication of the first reports of osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates in 2003, a call for national multidisciplinary guidelines based upon a systematic review of the current evidence was made by the Canadian Association of Oral and Maxillofacial Surgeons (CAOMS) in association with national and international societies concerned with ONJ. The purpose of the guidelines is to provide recommendations regarding diagnosis, identification of at-risk patients, and prevention and management strategies, based on current evidence and consensus. These guidelines were developed for medical and dental practitioners as well as for oral pathologists and related specialists. METHODS: The multidisciplinary task force established by the CAOMS reviewed all relevant areas of research relating to ONJ associated with bisphosphonate use and completed a systematic review of current literature. These evidence-based guidelines were developed utilizing a structured development methodology. A modified Delphi consensus process enabled consensus among the multidisciplinary task force members. These guidelines have since been reviewed by external experts and endorsed by national and international medical, dental, oral surgery, and oral pathology societies. RESULTS: RECOMMENDATIONS regarding diagnosis, prevention, and management of ONJ were made following analysis of all current data pertaining to this condition. ONJ has many etiologic factors including head and neck irradiation, trauma, periodontal disease, local malignancy, chemotherapy, and glucocorticoid therapy. High-dose intravenous bisphosphonates have been identified as a risk factor for ONJ in the oncology patient population. Low-dose bisphosphonate use in patients with osteoporosis or other metabolic bone disease has not been causally linked to the development of ONJ. Prevention, staging, and treatment recommendations are based upon collective expert opinion and current data, which has been limited to case reports, case series, surveys, retrospective studies, and 2 prospective observational studies. RECOMMENDATIONS: In all oncology patients, a thorough dental examination including radiographs should be completed prior to the initiation of intravenous bisphosphonate therapy. In this population, any invasive dental procedure is ideally completed prior to the initiation of high-dose bisphosphonate therapy. Non-urgent procedures are preferably delayed for 3 to 6 months following interruption of bisphosphonate therapy. Osteoporosis patients receiving oral or intravenous bisphosphonates do not require a dental examination prior to initiating therapy in the presence of appropriate dental care and good oral hygiene. Stopping smoking, limiting alcohol intake, and maintaining good oral hygiene should be emphasized for all patients receiving bisphosphonate therapy. Individuals with established ONJ are most appropriately managed with supportive care including pain control, treatment of secondary infection, removal of necrotic debris, and mobile sequestrate. Aggressive debridement is contraindicated. CONCLUSION: Our multidisciplinary guidelines, which provide a rational evidence-based approach to the diagnosis, prevention, and management of bisphosphonate-associated ONJ in Canada, are based on the best available published data and the opinion of national and international experts involved in the prevention and management of ONJ.