Efficacy and safety of direct oral anticoagulants approved for cardiovascular indications: Systematic review and meta-analysis.

BACKGROUND: Direct oral anticoagulants (DOACs) have emerged as promising alternatives to vitamin K antagonists (VKAs) for patients with non-valvular atrial fibrillation (NVAF) or venous thromboembolism (VTE). Few meta-analyses have included all DOACs that have received FDA approval for these cardiovascular indications, and their overall comparisons against VKAs have shortcomings in data and methods. We provide an updated overall assessment of the efficacy and safety of those DOACs at dosages currently approved for NVAF or VTE, in comparison with VKAs. METHODS: We used data from Phase 3 randomized trials that compared an FDA-approved DOAC with VKA for primary prevention of stroke in patients with NVAF or for treatment of acute VTE. RESULTS: Among trial participants with NVAF, DOAC recipients had a lower risk of stroke or systemic embolism [Pooled Odds Ratio (OR) 0.76, 95% Confidence Interval (CI) (0.68-0.84)], any stroke (0.80, 0.73-0.88), systemic embolism (0.56, 0.34-0.93), and total mortality (0.89, 0.84-0.95). Safety outcomes also showed a lower risk of fatal, major, and intracranial bleeding but higher risk for gastrointestinal bleeding (GIB). Patients with acute VTE randomized to DOACs had comparable risk of recurrent VTE and death (OR 0.88, 95% CI 0.75-1.03), recurrent DVT (0.83, 0.66-1.05), recurrent non-fatal PE (0.97, 0.75-1.25), and total mortality (0.94, 0.79-1.12). Safety outcomes for DOACs showed a lower risk of major, fatal, and intracranial bleeding, but similar risk of GIB. CONCLUSIONS: Patients receiving DOACs for NVAF had predominantly superior efficacy and safety. Patients who were treated with DOACs for acute VTE had non-inferior efficacy, but an overall superior safety profile.

Coronary Artery Calcium Scoring in Current Clinical Practice: How to Define Its Value?

OPINION STATEMENT: Detecting subclinical atherosclerosis with coronary artery calcium (CAC) is promising for identifying individuals at risk for cardiovascular events and appears to be a robust tool for guiding initiation of appropriate and timely primary prevention strategies. However, how do we best determine its clinical value? It is clear that traditional risk prediction models based primarily on age, gender, and risk factors are insufficient for ideal personalization of risk estimation. It is now well established from epidemiologic studies that CAC adds to traditional risk scores for a more accurate risk prediction. However, such traditional epidemiology studies have limitations in establishing "clinical value," and they must be supplemented by additional data before being translated into strong recommendations in clinical practice guidelines. Fortunately, over the last few years, the research around CAC has matured to include data supporting enhanced clinician-patient risk discussions, shared decision-making, flexible risk factor treatment goals, specific clinical decision algorithms, as well as favorable cost-effectiveness analyses. We had moved from a time when we asked "if CAC adds to the risk score" to a time when we are asking "does CAC facilitate a shared decision-making model matching risk, treatment, and patient preferences?" A new risk calculator incorporating CAC into global risk scoring, and 2017 guidelines on the use of CAC published by the Society of Cardiovascular Computed Tomography (SCCT), reflect this new approach. In this article, we review the recent transition to this more clinically relevant CAC research that may support a stronger recommendation for its use in future prevention guidelines.

Decade-Long Trends (2001 to 2011) in the Use of Evidence-Based Medical Therapies at the Time of Hospital Discharge for Patients Surviving Acute Myocardial Infarction.

Optimization of medical therapy during discharge planning is vital for improving patient outcomes after hospitalization for acute myocardial infarction (AMI). However, limited information is available about recent trends in the prescribing of evidence-based medical therapies in these patients, especially from a population-based perspective. We describe decade-long trends in the discharge prescribing of aspirin, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, ß blockers, and statins in hospital survivors of AMI. The study population consisted of 5,253 patients who were discharged from all 11 hospitals in central Massachusetts after AMI in 6 biennial periods from 2001 to 2011. Combination medical therapy (CMT) was defined as the prescription of all 4 cardiac medications at hospital discharge. The average age of this patient population was 69.2 years and 57.7% were men. Significant increases were observed in the use of CMT, from 25.6% in 2001 to 48.7% in 2011, with increases noted for each of the individual cardiac medications examined. Subgroup analysis also showed improvement in discharge prescriptions for P2Y12 inhibitors in patients who underwent a percutaneous coronary intervention. Presence of a do-not-resuscitate order, before co-morbidities, hospitalization for non-ST-segment elevation myocardial infarction, admission to a nonteaching hospital, and failure to undergo cardiac catheterization or a percutaneous coronary intervention were associated with underuse of CMT. In conclusion, our study demonstrates encouraging trends in the prescribing of evidence-based medications at hospital discharge for AMI. However, certain patient subgroups continue to be at risk for underuse of CMT, suggesting the need for strategies to enhance compliance with current practice guidelines.

Decade Long Trends (2001-2011) in Duration of Pre-Hospital Delay Among Elderly Patients Hospitalized for an Acute Myocardial Infarction.

BACKGROUND: Early intervention with medical and/or coronary revascularization treatment approaches remains the cornerstone of the management of patients hospitalized with acute myocardial infarction (AMI). However, several patient groups, especially the elderly, are known to delay seeking prompt medical care after onset of AMI-associated symptoms. Current trends, and factors associated with prolonged prehospital delay among elderly patients hospitalized with AMI, are incompletely understood. METHODS AND RESULTS: Data from a population-based study of patients hospitalized at all 11 medical centers in central Massachusetts with a confirmed AMI on a biennial basis between 2001 and 2011 were analyzed. Information about duration of prehospital delay after onset of acute coronary symptoms was abstracted from hospital medical records. In patients 65 years and older, the overall median duration of prehospital delay was 2.0 hours, with corresponding median delays of 2.0, 2.1, and 2.0 hours in those aged 65 to 74 years, 75 to 84 years, and in patients 85 years and older, respectively. There were no significant changes over time in median delay times in each of the age strata examined in both crude and multivariable adjusted analyses. A limited number of patient characteristics were associated with prolonged delay in this patient population. CONCLUSIONS: The results of this community-wide study demonstrate that delay in seeking prompt medical care continues to be a significant problem among elderly patients hospitalized with AMI. The lack of improvement in the timeliness of patients' care-seeking behavior during the years under study remains of considerable clinical and public health concern.

Decade-Long Trends (2001-2011) in the Incidence and Hospital Death Rates Associated with the In-Hospital Development of Cardiogenic Shock after Acute Myocardial Infarction.

BACKGROUND: Limited information is available about relatively contemporary trends in the incidence and hospital case-fatality rates of cardiogenic shock in patients hospitalized with acute myocardial infarction. The purpose of this population-based study was to describe decade long trends (2001-2011) in the incidence and hospital case-fatality rates for patients who developed cardiogenic shock during hospitalization for an acute myocardial infarction. METHODS AND RESULTS: The study population consisted of 5686 residents of central Massachusetts hospitalized with acute myocardial infarction at all 11 medical centers in the Worcester, MA, metropolitan area during 6 biennial periods between 2001 and 2011, who did not have cardiogenic shock at the time of hospital presentation. On average, 3.7% of these patients developed cardiogenic shock during their acute hospitalization with nonsignificant and inconsistent trends noted over time in both crude (3.7% in 2001/2003; 4.5% in 2005/2007; 2.7% in 2009/2011; P=0.19) and multivariable adjusted analyses. The overall in-hospital case-fatality rate for patients who developed cardiogenic shock was 41.4%. The crude and multivariable adjusted odds of dying after cardiogenic shock declined during the most recent study years (47.1% dying in 2001/2003, 42.0% dying in 2005/2007, and 28.6% dying in 2009/2011). Increases in the use of evidence-based cardiac medications, and interventional procedures paralleled the increasing hospital survival trends. CONCLUSIONS: We found suggestions of a decline in the death, but not incidence, rates of cardiogenic shock over time. These encouraging trends in hospital survival are likely because of advances in the early recognition and aggressive management of patients who develop cardiogenic shock.

Risk factors and comorbidities in a community-wide sample of patients hospitalized with acute systolic or diastolic heart failure: the Worcester Heart Failure Study.

OBJECTIVES: Few epidemiological studies have examined differences in the prevalence of risk factors and comorbidities in patients with systolic heart failure (HF), as compared with those with diastolic HF. METHODS: We analyzed data from 1426 residents of the Worcester (MA) metropolitan area hospitalized at all 11 greater Worcester medical centers for acute HF during 1995 and 2000 who had data available on ejection fraction (EF) findings during hospitalization. The analysis was conducted based on the presence of either normal (diastolic HF) as compared with reduced (systolic HF) EF, using an EF cutpoint of at least 50%. RESULTS: The average age of study patients was 71 years, 56% were women, and 43% had diastolic HF. Patients with diastolic HF were more likely to be older, female, obese, and to have higher systolic blood pressures and lower heart rates at the time of hospital presentation than patients with systolic HF. In contrast, patients with systolic HF had a greater prevalence of diabetes, previous myocardial infarction, and a history of alcohol abuse as compared with patients with diastolic HF. In multivariate analyses, the strongest metabolic correlates of diastolic HF were obesity, hypertension, and clustered metabolic risk factors; diabetes was associated with the occurrence of systolic HF. CONCLUSION: The results of our population-based investigation show that multiple risk factors and comorbidities are present in patients with systolic and diastolic HF. Consideration of these comorbidities and risk factors should be taken into account in distinguishing patients with diastolic HF from those with systolic HF and in their optimal management.

Infliximab therapy in pediatric Crohn's disease: a review.

Anti-tumor necrosis factor alpha (TNF-α) therapy has re-defined our treatment paradigms in managing patients with Crohn's disease (CD) and ulcerative colitis. Although the ACCENT studies showed proven efficacy in the induction and maintenance of disease remission in adult patients with moderate to severe CD, the pediatric experience was instrumental in bringing forth the notion of "top-down" therapy to improve overall clinical response while reducing the risk of complications resulting from long-standing active disease. Infliximab has proven efficacy in the induction and maintenance of disease remission in children and adolescents with CD. In an open-labeled study of 112 pediatric patients with moderate to severe CD, 58% achieved clinical remission on induction of infliximab (5 mg/kg) therapy. Among those patients who achieved disease remission, 56% maintained disease remission on maintenance (5 mg/kg every 8 weeks) therapy. Longitudinal follow-up studies have also shown that responsiveness to infliximab therapy also correlates well with reduced rates of hospitalization, and surgery for complication of long-standing active disease, including stricture and fistulae formation. Moreover, these children have also been shown to improve overall growth while maintaining an effective disease remission. The pediatric experience has been instructive in suggesting that the early introduction of anti-TNF-α therapy may perhaps alter the natural history of CD in children, an observation that has stimulated a great deal of interest among gastroenterologists who care for adult patients with CD.