Direct Oral Anticoagulants in Addition to Antiplatelet Therapy for Secondary Prevention after Acute Coronary Syndromes: a Review.

PURPOSE OF REVIEW: As the management of acute coronary syndrome (ACS) continues to evolve, many old practices proved to be of a little benefit and other approaches established the new pillars of modern medicine. Treating ACS patients with dual antiplatelet therapy (DAPT) for a year by combining aspirin and a P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel) has resulted in better outcomes and is currently the standard of therapy. However, owing to the persistent activation of the coagulation cascade, patients may continue to experience recurrent ischemia and high mortality rates despite compliance with the dual antiplatelet therapy. Research is underway to establish new treatment modalities for secondary prevention post-ACS, including the use of the novel direct oral anticoagulants (DOACs). RECENT FINDINGS: Multiple trials have been conducted to evaluate the use of DOACs for the secondary prevention after ACS. Recent emerging data showed that the addition of rivaroxaban in a very low dose of 2.5 mg twice daily to the regular DAPT regimen after ACS is beneficial in the reduction of major cardiovascular events, including recurrent myocardial infarction (MI) and strokes. On the other hand, other DOACs, including apixaban, did not show similar efficacy and did not improve the cardiovascular outcomes. Patients who experience an ACS continue to suffer long-term consequences and thromboembolic complications. Many studies have shown that after the initial ACS event, patients remain in a hypercoagulable state and are more prone to recurrent ischemic attacks including stroke, recurrent MI, or unstable angina (UA). With the objective of seeking better outcomes, it is imperative to explore more aggressive anticoagulation strategies in ACS patients. In this article, we discuss the progress that was made and the limitations we face regarding the role of different anticoagulants in this setting.

Fractures frequently occur in older cancer patients: the MD Anderson Cancer Center experience.

PURPOSE AND INTRODUCTION: A growing number of cancer patients are older adults aged 65 years and older. Patients with cancer are at increased risk for developing osteoporosis, falls, and fractures. We sought to identify the incidence of fractures in older adults who underwent cancer care between January 2013 and December 2015. METHODS: A comprehensive geriatric assessment was performed, and bone densitometry was measured at baseline, with a 2-year follow-up. RESULTS: In this study, among 304 patients with gastrointestinal, urologic, breast, lung, and gynecologic cancers we evaluated, and who completed the bone density testing (n = 199), 80% had osteoporosis or low bone mass (osteopenia). There was a higher prevalence of osteoporosis in cancer patients (40 vs. 16%, p = 0.05) than in population studies. Vitamin D insufficiency (< 30 ng/ml) was identified in 49% of tested cases (n = 245). Risk factors for low bone mass or osteoporosis were advanced age (p = 0.05), malnutrition (p = 0.04), and frailty (p = 0.01). Over the following 2 years (median follow-up 18 months), there was an incidence of fractures of 110 per 1000 person-years, or 2.8 times higher than reported in individuals without cancer. Risk factors for fractures included advanced age (70-79 vs. 60-69 years, p = 0.05) and frailty (p = 0.03). CONCLUSION: Most older cancer patients studied have osteoporosis or low bone mass, resulting in an almost 3-fold increase in fracture risk as compared to epidemiologic studies. Bone health issues are commonly seen in older cancer patients, we recommend universal bone density testing. The initiation of antiresorptive treatment when findings are of osteopenia or osteoporosis will reduce the risk of fractures.

The importance of electrode-tissue proximity in creating pulsed field ablation lesions: insights from a sub-acute preclinical model.

BACKGROUND: We sought to evaluate the anatomic and functional lesion development over time at different atrial sites immediately following delivery of pulsed field ablation (PFA). METHODS: Using a porcine model, PFA ablations were performed in the superior vena cava (SVC), right atrial lateral wall (RA), left atrial appendage (LAA), and right superior pulmonary vein (RSPV) using four different PFA profiles. Mapping was done sequentially in 5-20-min increments up to 280-min post lesion delivery for low voltage area (LVA) assessment and conduction velocity. Lesion characteristics were noted with voltage mapping immediately post ablation and at the serial time points. RESULTS: In 9 animals, 33 sites were ablated. None of the four different profiles across all sites showed any statistical difference on acute lesion formation or persistence. Higher tissue contact was observed in the SVC and RSPV and lower tissue contact was observed in the LAA and RA locations. Higher contact areas were noted to have higher density electroanatomic low voltage area (LVA) (12/14 vs 5/18, p = 0.01) and larger lesions on gross pathology (2 /14 vs 6/16, p = 0.01) compared to lower contact areas. Lesion regression occurred in 16/33 sites. Sustained lesions were significantly more prevalent in higher versus lower contact sites (65% vs 38%, p = 0.037). CONCLUSION: The development of significant and durable lesions for PFA in a porcine model appears to be dependent on tissue proximity and contact.

Overall survival in older patients with cancer.

OBJECTIVES: A growing number of patients with cancer are older adults. We sought to identify the predictors for overall survival (OS) in older adults with solid tumour and haematological malignancies between January 2013 and December 2016. METHODS: Retrospective cohort study. A comprehensive geriatric assessment was performed, with a median follow-up of 12.8 months. ANALYSIS: univariate and multivariate Cox proportional hazards regression analysis. RESULTS: In this study, among the 455 patients with last follow-up date or date of death, 152 (33.4%) died during the follow-up. The median follow-up is 12.8 months (range 0.2-51.1 months) and the median OS is 20.5 months (range 0.3-44.5 months). Among all older patients with cancer, predictors of OS included male gender, cancer stage, malnutrition, history of smoking, heavy alcohol use, frailty, weight loss, major depression, low body weight and nursing home residence. Traditional performance scores (Eastern Cooperative Oncology Group (ECOG) and Karnofsky Performance Scale (KPS)) were predictors of OS. Independent predictors included age >85 years and haematological malignancies. Among solid tumours (n=311) in addition to the above predictors, comorbidity, gait speed and vitamin D deficiency were associated with OS. CONCLUSIONS: We identified specific geriatric factors associated with OS in older patients with cancer, and comparable in predictive ability to traditional performance scores such as KPS and ECOG. Prospective studies will be necessary to confirm our findings.

Entresto, a New Panacea for Heart Failure?

Heart Failure (HF) is one of the main healthcare burdens in the United States and in the world. Many drugs are approved and used in practice for management of this condition; including beta blockers, diuretics, aldosterone antagonists, Angiotensin Converting Enzyme Inhibitors (ACEI's), and Angiotensin Receptor Blockers (ARBs). Recently, the Food and Drug Administration (FDA) approved a drug with brand name Entresto (Sacubitril/Valsartan or LCZ696), an angiotensin receptor neprilysin inhibitor for the use in Heart Failure with Reduced Ejection Fraction (HFrEF) patients instead of ACEI's and ARBs. The drug works through angiotensin receptor blockage via valsartan as well as neprilysin inhibition with sacubitril. This represented a new milestone in managing heart failure patients and provided yet another therapy in our armamentarium. This article reviews the stages that led to the development of this drug, the failure of its preceding agents, the lessons we have learnt, and the current trials of Entresto for new indications.

Neurocognitive deficits in older patients with cancer.

OBJECTIVE: To assess cognitive function in older adults undergoing cancer care. MATERIALS AND METHODS: This is a cross-sectional study, in the University of Texas MD Anderson Cancer Center, in older adults undergoing cancer care. Comprehensive geriatric assessments were conducted prior to surgery, chemotherapy or allogeneic stem cell transplantation, at the Program for Healthy Aging from January 1, 2013 through March 31, 2015. Cognitive assessment was conducted through personal and family interview, and the Montreal cognitive assessment (MoCA). Functional, physical, nutritional, social support, comorbidity assessment and medication review were conducted. ANALYSIS: Patients with mild cognitive impairment (MCI) or dementia were compared to patients who were cognitively intact. RESULTS: One hundred and ninety-two patients underwent geriatric assessment, mean (±SD) age was 78 ±â€¯7 years, 121 (63%) had some degree of neurocognitive deficit, with 64 patients (33%) presenting with major neurocognitive deficit (dementia), and 57 cases (30%), minor neurocognitive deficit (MCI). Early stage dementia was evident in 50% of cases, moderate stage in 32%, and severe stage in 18%. The prevalence of dementia and MCI were higher than in the general population studies (70-79 years). Associated factors for neurocognitive deficits as compared to older patients with cancer with normal cognition, included a higher comorbidity index (p = 0.04), stroke (p = 0.03), metastatic disease (p = 0.04), and warfarin use (p = 0.03). CONCLUSION: Neurocognitive deficits (MCI and dementia) are more common in older adults with cancer. Factors associated with neurocognitive deficits include high comorbidity, stroke, warfarin use and metastatic cancer. Identification and management of these conditions is of great relevance in the course of cancer therapy.