Showing papers by "Elliott M. Antman published in 2014"
TL;DR: A prespecified meta-analysis of all 71,683 participants included in the RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48 trials offered clinicians a more comprehensive picture of the new oral anticoagulants as a therapeutic option to reduce the risk of stroke in this patient population.
3,729 citations
TL;DR: In a contemporary AF population, LA structure and function were increasingly abnormal with a greater electrical burden of AF and higher stroke risk estimated by the CHADS2 score, suggesting that the assessment of LA function may add important incremental information in the evaluation of AF patients.
Abstract: Aims The complex relationship between left atrial (LA) structure and function, electrical burden of atrial fibrillation (AF) and stroke risk is not well understood. We aimed to describe LA structure and function in AF.
Methods and results Left atrial structure and function was assessed in 971 subjects enrolled in the echocardiographic substudy of ENGAGE AF-TIMI 48. Left atrial size, emptying fraction (LAEF), and contractile function were compared across AF types (paroxysmal, persistent, or permanent) and CHADS2 scores as an estimate of stroke risk. The majority of AF patients (55%) had both LA enlargement and reduced LAEF, with an inverse relationship between LA size and LAEF ( R = −0.57, P < 0.001). With an increasing electrical burden of AF and higher CHADS2 scores, LA size increased and LAEF declined. Moreover, 19% of AF subjects had impaired LAEF despite normal LA size, and LA contractile dysfunction was present even among the subset of AF subjects in sinus rhythm at the time of echocardiography.
Conclusions In a contemporary AF population, LA structure and function were increasingly abnormal with a greater electrical burden of AF and higher stroke risk estimated by the CHADS2 score. Moreover, LA dysfunction was present despite normal LA size and sinus rhythm, suggesting that the assessment of LA function may add important incremental information in the evaluation of AF patients. Clinical Trial Registration: ; ID = [NCT00781391][1].
[1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00781391&atom=%2Fehj%2F35%2F22%2F1457.atom
168 citations
TL;DR: Achieving high levels of adherence to each and all guideline-recommended post-myocardial infarction secondary prevention medication is associated with improved event-free survival, and lower levels of adhere appear less protective.
159 citations
TL;DR: Application of this hs-cTnI assay identified a clinically relevant higher risk of recurrent events among patients with NSTE-ACS, even at very low troponin concentrations.
Abstract: Background: High-sensitivity assays for cardiac troponin enable more precise measurement of very low concentrations and improved diagnostic accuracy. However, the prognostic value of these measurements, particularly at low concentrations, is less well defined.
Methods: We evaluated the prognostic performance of a new high-sensitivity cardiac troponin I (hs-cTnI) assay (Abbott ARCHITECT) compared with the commercial fourth generation cTnT assay in 4695 patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS) from the EARLY-ACS (Early Glycoprotein IIb/IIIa Inhibition in NSTE-ACS) and SEPIA-ACS1-TIMI 42 (Otamixaban for the Treatment of Patients with NSTE-ACS–Thrombolysis in Myocardial Infarction 42) trials. The primary endpoint was cardiovascular death or new myocardial infarction (MI) at 30 days. Baseline cardiac troponin was categorized at the 99th percentile reference limit (26 ng/L for hs-cTnI; 10 ng/L for cTnT) and at sex-specific 99th percentiles for hs-cTnI.
Results: All patients at baseline had detectable hs-cTnI compared with 94.5% with detectable cTnT. With adjustment for all other elements of the TIMI risk score, patients with hs-cTnI ≥99th percentile had a 3.7-fold higher adjusted risk of cardiovascular death or MI at 30 days relative to patients with hs-cTnI <99th percentile (9.7% vs 3.0%; odds ratio, 3.7; 95% CI, 2.3–5.7; P < 0.001). Similarly, when stratified by categories of hs-cTnI, very low concentrations demonstrated a graded association with cardiovascular death or MI ( P -trend < 0.001). Use of sex-specific cutpoints did not improve prognostic performance. Patients with negative fourth generation cTnT (<10 ng/L) but hs-cTnI ≥26 ng/L were at increased risk of cardiovascular death/MI compared to those with hs-cTnI <26 ng/L (9.2% vs 2.9%, P = 0.002).
Conclusions: Application of this hs-cTnI assay identified a clinically relevant higher risk of recurrent events among patients with NSTE-ACS, even at very low troponin concentrations.
72 citations
TL;DR: Edoxaban, a factor Xa inhibitor, was not found to be inferior to warfarin for the prevention of stroke or systemic embolic events in patients with atrial fibrillation and was associated with significantly less bleeding.
Abstract: BACKGROUND: Atrial fibrillation (AF) and heart failure (HF) have emerged as the two epidemics of cardiovascular (CV) disease. The prevalence of AF increases with the severity of HF and contributes to HF disability. Among patients treated with vitamin K antagonists (VKAs), symptomatic HF is an independent risk factor for lower time in therapeutic range (TTR), which reduces the efficacy and safety of VKAs. METHODS: In the ENGAGE AF-TIMI 48 trial, both once-daily regimens of the direct oral factor Xa inhibitor edoxaban [high (HDE) and low dose (LDE)], were non inferior to warfarin (W) for prevention of stroke and systemic embolic events (SEE) in patients with AF and were associated with lower rates of bleeding. We evaluated the safety and the efficacy of edoxaban compared with W in patients with HF presenting with different severity of functional limitation (NYHA class). RESULTS: Among 21,105 patients enrolled 8,981(43%) had no history of HF, 9,489 (45%) had history of HF and a NYHA class I-II, whereas 2,635...
54 citations
TL;DR: The efficacy of prasugrel versus clopidogrel was consistent irrespective of the timing of PCI, particularly in preventing nonprocedural events.
Abstract: Objectives This study sought to evaluate the efficacy of prasugrel versus clopidogrel in ST-segment elevation myocardial infarction (STEMI) by the timing of percutaneous coronary intervention (PCI). Background Treatment strategies and outcomes for patients with STEMI may differ when treated with primary compared with secondary PCI. Methods STEMI patients in the TRITON–TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis In Myocardial Infarction 38) were randomized to prasugrel or clopidogrel on presentation if primary PCI was intended or later during secondary PCI. Primary PCI was defined as within 12 h of symptom onset. The primary endpoint was cardiovascular death, myocardial infarction (MI), or stroke. Because periprocedural MI is difficult to assess in the setting of STEMI, we performed analyses excluding these events. Results Reductions in the primary endpoint with prasugrel versus clopidogrel (hazard ratio [HR]: 0.79; 95% confidence interval [CI]: 0.65 to 0.97; p = 0.022) were consistent between primary and secondary PCI patients at 15 months (HR: 0.89; 95% CI: 0.69 to 1.13 vs. HR: 0.65; 95% CI: 0.46 to 0.93; p interaction = 0.15). However, a tendency toward a difference in treatment effect at 30 days (HR: 0.68; 95% CI: 0.54 to 0.87; p = 0.002) was observed between primary and secondary PCI patients (HR: 0.81; 95% CI: 0.60 to 1.09 vs. HR: 0.51; 95% CI: 0.34 to 0.76; p interaction = 0.06). When periprocedural MI was excluded, the efficacy of prasugrel remained consistent among primary and secondary PCI patients at 30 days (HR: 0.53; 95% CI: 0.34 to 0.81 vs. HR: 0.44; 95% CI: 0.22 to 0.88; p interaction = 0.68) and 15 months (HR: 0.76; 95% CI: 0.56 to 1.03 vs. HR: 0.75; 95% CI: 0.46 to 1.21; p interaction = 0.96). Conclusions The efficacy of prasugrel versus clopidogrel was consistent irrespective of the timing of PCI, particularly in preventing nonprocedural events. (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction 38; NCT00097591 )
46 citations
TL;DR: The ENGAGE AF-TIMI 48 transition plan protected patients from an excess of thrombotic and bleeding events and should be helpful in clinical practice when patients are transitioned between oral anticoagulants.
46 citations
TL;DR: In patients with atrial fibrillation, once-daily edoxaban was as effective as warfarin in preventing all strokes, with significant reductions in various subtypes of intracranial bleeding.
Abstract: Background and Purpose—The once-daily oral factor Xa inhibitor, edoxaban, is as effective as warfarin in preventing stroke and systemic embolism while decreasing bleeding in a phase III trial of patients with atrial fibrillation at moderate–high stroke risk. Limited data regarding cerebrovascular events with edoxaban were reported previously. Methods—We analyzed the subtypes of cerebrovascular events in 21 105 patients participating in Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) comparing outcomes among patients randomized to warfarin versus 2 edoxaban regimens (high dose, low dose). The primary end point for this prespecified analysis of cerebrovascular events was all stroke (ischemic plus hemorrhagic), defined as an abrupt onset of focal neurological deficit because of infarction or bleeding with symptoms lasting ≥24 hours or fatal in <24 hours. Independent stroke neurologists unaware of treatment adjudicate...
45 citations
TL;DR: A 2-day interactive forum was convened to discuss the current status and future implications of reducing sodium in the food supply and to identify opportunities for stakeholder collaboration as mentioned in this paper. But none of the participants were able to attend the entire workshop.
Abstract: Background—A 2-day interactive forum was convened to discuss the current status and future implications of reducing sodium in the food supply and to identify opportunities for stakeholder collaboration. Methods and Results—Participants included 128 stakeholders engaged in food research and development, food manufacturing and retail, restaurant and food service operations, regulatory and legislative activities, public health initiatives, healthcare, academia and scientific research, and data monitoring and surveillance. Presentation topics included scientific evidence for sodium reduction and public health policy recommendations; consumer sodium intakes, attitudes, and behaviors; food technologies and solutions for sodium reduction and sensory implications; experiences of the food and dining industries; and translation and implementation of sodium intake recommendations. Facilitated breakout sessions were conducted to allow for sharing of current practices, insights, and expertise. Conclusions—A well-estab...
40 citations
TL;DR: Author(s): Josephson, Scott; Zoghbi, WA; Duncan, T; Antman, E; Barbosa, M; Champagne, B; Chen, D; Gamra, H; Harold, JG; Komajda, M.
Abstract: Author(s): Josephson, Scott; Zoghbi, WA; Duncan, T; Antman, E; Barbosa, M; Champagne, B; Chen, D; Gamra, H; Harold, JG; Komajda, M
31 citations
TL;DR: In TRITON-TIMI 38, the safety and efficacy outcomes of prasugrel compared with those of clopidogrel were directionally consistent regardless of aspirin dose, although only the primary efficacy endpoint achieved statistical significance.
TL;DR: Clinical research has reached a pivotal moment, not only with the exponential expansion of tools for data capture as well as data sources, but also with the opportunity to reevaluate how to integrate the information to optimize medical decision making.
Abstract: Classic health care research has centered on studying a group of individuals and then extrapolating the findings to the general population. In this context, evaluating the association between nonrandomized exposures and clinical outcomes can yield interesting, hypothesis-generating correlations, but assembling evidence to suggest a causal relationship has focused on testing the relationship between randomized exposures and clinical outcomes 1 (Figure). Clinical research has reached a pivotal moment, not only with the exponential expansion of tools for data capture as well as data sources, but also with the opportunity to reevaluate how to integrate the information to optimize medical decision making. First, increasingly more data will beavailableintheformofadvanceddiagnostics,electronic health records, and mobile digital technologies. It is now possible to define more precisely individuals or cohorts of individuals when planning clinical studies. Second, data sources are coalescing. Instead of extrapolating findings to a broader population, it is possible to study that broader population.Ifrigorousmethodologicapproachesthathave emerged from epidemiology studies and clinical trials are applied in these settings, then the promise of delivering on population and personalized medicine could be realized. Examples are emerging for which medical strategies
Journal Article•
TL;DR: The authors are on the cusp of a new era in global health policy that could transform the lives of millions worldwide, and whether cardiovascular health is part of this transformation will be largely determined within the next few months.
Abstract: We are on the cusp of a new era in global health policy that could transform the lives of millions worldwide. Whether cardiovascular health is part of this transformation will be largely determined within the next few months, when the United Nations will debate and decide upon Sustainable
TL;DR: The ENGAGE AF-TIMI 48 trial showed that both the high (HD) and low dose (LD) regimens of the once daily oral factor Xa inhibitor edoxaban were non-inferior to well-managed warfarin in preventing stroke and systemic embolic events (SEE) while reducing major bleeding.
Abstract: Background: Elderly patients with atrial fibrillation (AF) treated with anticoagulants are at higher risk of both ischemic and bleeding events compared to younger patients. Intracranial bleeding (ICH) remains one of the most concerning complications of anticoagulation therapy, and risk is strongly related to age. The ENGAGE AF-TIMI 48 trial showed that both the high (HD) and low dose (LD) regimens of the once daily oral factor Xa inhibitor edoxaban were non-inferior to well-managed warfarin (TTR 68.4%) in preventing stroke and systemic embolic events (SEE) while reducing major bleeding. Methods: 21,105 patients were enrolled in ENGAGE-TIMI 48 trial and stratified into pre-specified age categories: Results: Regardless of treatment, the risk of major bleeding and stroke/SEE increased with age (p Conclusion: The efficacy and safety of edoxaban compared to well-managed warfarin are consistent regardless of age in patients with AF. Due to the higher risk of bleeding with increasing age, the absolute benefits of edoxaban are greater in the elderly.
TL;DR: 2 new versions of clinical practice guidelines (CPGs) on perioperative cardiovascular evaluation from the American College of Cardiology, the American Heart Association, and the European Society of cardiology are announced.
Abstract: The American College of Cardiology (ACC), the American Heart Association (AHA), and the European Society of Cardiology (ESC) are pleased to announce the publication of 2 new versions of clinical practice guidelines (CPGs) on perioperative cardiovascular evaluation from our respective organizations.1–3
These revisions were begun independently, dictated both by emerging, new information regarding the topic and the controversy regarding the legitimacy of data from previously published pivotal trials. Accordingly, the leadership of these international organizations recognized the importance of scientific collaboration and writing committee coordination for the benefit of the worldwide cardiology community. A joint statement was therefore posted in August 20134–6 to indicate that the respective CPGs were under revision and to provide some guidance regarding perioperative …
TL;DR: January 11, 2014, marks the 50th anniversary of a significant milestone in the authors' nation's public health, when the first Surgeon General's Report on Smoking and Health was released.
Abstract: January 11, 2014, marks the 50th anniversary of a significant milestone in our nation's public health. It was on this date in 1964 that US Surgeon General, Dr. Luther Terry, courageously released the first Surgeon General's Report on Smoking and Health.[1][1] This landmark report transformed the way
TL;DR: The cycle of research begins with identification of an idea, design of the study to answer the scientific question that is posed, conducting and analyzing the findings, and publishing the results.
Abstract: The cycle of research begins with identification of an idea, design of the study to answer the scientific question that is posed, conducting and analyzing the findings, and publishing the results. Figure 1 shows the position of the open source, open data, and open access components of the open science concept superimposed on the cycle of research.⇓ One can readily advocate, in principle, for open data to provide doctors and their patients all the data needed for optimum decision-making (figure 2).⇓ 1
Figure 1 Research cycle. JAHA— Journal of the American Heart Association is an example of an open access publication
Figure 2 Advantages of open data
To illustrate the issues involved, however, consider the flow of data when a clinical trial is completed (figure 3).⇓ A series of raw databases are created. They are populated from the case report forms, and contain patient level information on such topics as baseline demographics, concomitant medications, study drug compliance, suspected endpoint events, clinical laboratory data, and adverse events. Other raw databases might include the final adjudication by the blinded endpoint committee as to whether an endpoint occurred, genetic data, quality of life survey results, and core laboratory data. A data dictionary is developed to link the information from the raw databases to several derived databases that cover items such as endpoints, time to event, and allocation to treatment arm. The derived databases are the source from which data tables are generated for preparation of manuscripts that ultimately appear in the medical …
TL;DR: The United Nations will debate and decide upon sustainable sustainable health policies that could transform the lives of millions worldwide as discussed by the authors, and cardiovascular health is part of this transformation will be largely determined within the next few months.
TL;DR: The meta-analysis compared outcomes in patients aged 75 years or older with those younger than 75 years and found that the effi cacy and safety of new oral anticoagulants was consistent irrespective of age, and disagreed with Opstelten and colleagues’ broad recommendation to only prescribe new oral anti-cancerants to patients younger than 80 years.
TL;DR: This is a PDF file of an unedited manuscript that has been accepted for publication and will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form.
TL;DR: Clinicians want to provide their patients with the best possible advice with respect to the management of cardiovascular risk, often implementing evidence-based clinical practice guidelines designed to improve health outcomes.
Abstract: The World Health Organization lists ischemic heart disease and stroke as the top 2 leading causes of death worldwide in 2011, responsible for 7 million and 6.2 million deaths, respectively.1 The concept of risk factors for atherosclerotic cardiovascular disease (CVD) was introduced in 1961, based on epidemiologic observations from the Framingham Heart Study. Hypertension and abnormal blood lipid levels were key risk factors shown to be associated with an increased risk of angina pectoris, myocardial infarction, and sudden cardiac death; later, stroke was identified as an important outcome as well, especially in women and racial/ethnic subgroups. Accordingly, clinicians want to provide their patients with the best possible advice with respect to the management of cardiovascular risk, often implementing evidence-based clinical practice guidelines designed to improve health outcomes.
Journal Article•
TL;DR: The safety profile of Edox may be particularly attractive in patients with AF who receive a combination of AP and anticoagulant therapy because of higher absolute risk of bleeding.
Abstract: BACKGROUND: Patients with atrial fibrillation (AF) who receive both antiplatelet (AP) and anticoagulant therapy are at markedly higher risk of bleeding. The ENGAGE AF-TIMI 48 trial showed that both the high- (HD) and low-dose (LD) regimens of the once-daily factor Xa inhibitor edoxaban (Edox) were as effective as well-managed warfarin (Warf) (median TTR 68.4%) in preventing stroke or systemic embolism (SEE) with significant reductions in major bleeding and cardiovascular mortality. In this study, we assessed the relative efficacy and safety of Edox as compared with Warf in patients with and without concomitant use of AP therapy.
METHODS: This was a randomized, double-blind, double-dummy trial comparing HD (60 mg daily, reduced to 30mg in patients with anticipated increased drug exposure) and LD (30 mg daily, reduced to 15mg) Edox with Warf. Dual AP therapy was prohibited while receiving study drug. Cox proportional hazards models were performed stratified by AP use at 3 months with treatment as a covariate.
RESULTS: Of the 21,105 patients, 4,912 (23%) were receiving AP therapy at 3 months (92% aspirin). Patients who received concomitant AP therapy had higher rates of major bleeding compared to patients who did not (Fig). Both Edox regimens had similar relative efficacy in preventing stroke or SEE compared with Warf regardless of concomitant AP use (Pint>0.10 for both) with consistent reductions in major bleeding (HD Edox vs. Warf: Pint=0.91; LD Edox vs. Warf: Pint=0.59). In patients randomized to LD Edox, AP therapy was associated with a further reduction in the net clinical outcome of death, stroke, SEE, or major bleeding (Pint=0.02) compared with Warf.
CONCLUSIONS: Regardless of concomitant AP therapy, both doses of Edox significantly reduced bleeding compared to well-managed Warf. The safety profile of Edox may be particularly attractive in patients with AF who receive a combination of AP and anticoagulant therapy because of higher absolute risk of bleeding.
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TL;DR: Two new versions of Clinical Practice Guidelines (CPGs) on Perioperative Cardiovascular Evaluation from the American College of Cardiology, the American Heart Association, and the European Society of Cardiological Evaluation are pleased to announce.
Abstract: This editorial refers to ‘2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management’[†][1], by The Joint Task Force on non-cardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA), on page 2383.
The American College of Cardiology (ACC), the American Heart Association (AHA), and the European Society of Cardiology (ESC) are pleased to announce the publication of two new versions of Clinical Practice Guidelines (CPGs) on Perioperative Cardiovascular Evaluation from our respective organizations.1–3
These revisions were begun independently, dictated both by emerging, new information regarding the topic and the controversy …
[1]: #fn-2
TL;DR: The optimal duration of dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) is not known and factors influencing DAPT duration are not well described.
Abstract: Background
The optimal duration of dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) is not known. Factors influencing DAPT duration are not well described.
Hypothesis
We hypothesized that continued DAPT 12 months beyond ACS would be associated with patient factors such as stent type and that it may be associated with lower rates of ischemic events.
Methods
The TIMI 38 Coronary Stent Registry (CSR) followed patients who completed the TRITON-TIMI 38 trial, received a stent, and were alive and event free. Continuation of DAPT was determined by the treating physician.
Results
The CSR enrolled 2110 patients (1679>12 months from index ACS) and followed for a median of 2.1 additional years. DAPT was continued in 554 (26%) and was more likely to be continued in patients with drug-eluting stents (DES; 54%) and in North America. The rate of cardiovascular death, MI, or stroke was 2.35% per year, and 13 patients (0.6%) experienced Academic Research Consortium definite or probable ST. Recurrent ischemic events were similar between patients who continued thienopyridine therapy and those who stopped at registry entry (P = 0.74 for cardiovascular death/MI/stroke; P = 0.72 for definite or probable ST). After propensity score adjustment, there was no significant difference in cardiovascular death/MI/stroke (P = 0.55) or bleeding (P = 0.51) with prolonged DAPT.
Conclusions
Patients stabilized for a year after ACS and stenting have low rates of ST relative to overall cardiovascular events. The decision to continue DAPT maybe associated with stent type (DES vs bare-metal stent) and region.
TL;DR: Focusing on disruptive innovations for development of medical therapeutics has the potential to bring us closer to the goal of precision medicine where safer, more effective treatments are discovered in a more efficient system.
Abstract: Clinical research plays a central role in the development of medical therapeutics, but the current system is estimated to take 10-15 years from initial discovery to regulatory approval, at a cost of approximately US$1 billion Contrast the paths by which 2 anticoagulant options for atrial fibrillation were discovered and ultimately established as treatment options in clinical medicine Warfarin was discovered by serendipity and compared with placebo in relatively small trials; this was associated with a low cost of development The new oral anticoagulants were synthesized to provide highly specific, targeted inhibition of critical steps in the coagulation system They were compared with warfarin for prevention of stroke and systemic embolic events in large, phase 3 trials; this resulted in very expensive development programs Neither of these paths is desirable for future development of therapeutics We need to focus on innovative approaches at the preclinical level (systems approach, greater use of inducible pluripotent stem cells, use of novel bioengineering platforms) and clinical trial level (adaptive design, greater use of new and emerging technology) Focusing on disruptive innovations for development of medical therapeutics has the potential to bring us closer to the goal of precision medicine where safer, more effective treatments are discovered in a more efficient system
Journal Article•
TL;DR: It is suggested that HD E is a high economic value therapeutic alternative relative to W for the prevention of stroke and SE in patients with AF and low dose E is likely to offer intermediate value from an economic perspective.
Abstract: Background: The ENGAGE AF-TIMI 48 trial demonstrated that both high dose (HD, 60 mg) and low dose (LD, 30 mg) once-daily regimens of edoxaban (E) were non-inferior to warfarin (W) for the prevention of stroke or systemic embolism (SE) in 21,105 patients with atrial fibrillation (AF), with significantly lower rates of bleeding and cardiovascular death. This study evaluated the economic value of E vs. W. Method: We assessed the cost-effectiveness of HD and LD E vs. W in US$ over the lifetime of AF patients using a Markov model based on data from the ENGAGE AF-TIMI 48 trial, US life-tables, and published literature on costs and long-term outcomes of non-fatal events in AF patients. ENGAGE AF-TIMI 48 trial data were used to derive age-adjusted event rates for W and hazard ratios for the relative impact of HD and LD E vs. W on embolic and bleeding complications. 2013 wholesale acquisition costs were used for W ($11/month) and E ($269.18/month, assumed as mean cost of marketed novel oral anticoagulants). Incremental cost-effectiveness ratio (ICER) thresholds of $150K per QALY gained proposed by AHA/ACC were used to differentiate between high, intermediate, and low value treatment options. Probabilistic sensitivity analyses evaluated the impact of model parameter uncertainty on ICERs. Results: For HD E vs. W, lifetime costs were $42,846 vs. $27,094, and QALYs were 7.249 vs. 6.910, respectively, yielding an ICER of $46,393/QALY gained. The ICER for LD E vs. W was $67,320/QALY. ICERS were lower for patients with no prior W use. For HD E, ICERs differed minimally by CHADS 2 score; for LD E ICER was considerably higher for the CHADS 2 4-6 subgroup due to increased risk of ischemic stroke with LD E. (Table). Conclusion: Despite higher acquisition costs, these results suggest that HD E is a high economic value therapeutic alternative relative to W for the prevention of stroke and SE in patients with AF. Low dose E is likely to offer intermediate value from an economic perspective.
TL;DR: High (HD) and low doses (LD) of the FXa inhibitor edoxaban (edox) were noninferior to warfarin in preventing stroke/systemic embolism (stroke/SEE) with less bleeding in the ENGAGE-AF trial.
TL;DR: A prespecified analysis of data from the 21,105 patients with AF enrolled into ENGAGE AF-TIMI 48, a randomized trial comparing two once-daily regimens of edoxaban (high- and low-dose) with warfarin for the prevention of stroke and systemic embolism found that 67 patients who met the primary endpoint had a systemic embolic event, of which 13% were fatal.
Abstract: Background: Atrial fibrillation (AF) is widely recognized as a major risk factor for stroke and systemic embolism. Multiple trials comparing warfarin with factor specific oral anticoagulants have demonstrated that the newer agents are at least as effective as and generally safer than warfarin. However, none of these studies has provided a detailed analyses regarding systemic embolism, the less frequent component of the primary endpoint. Methods and Results: We did a prespecified analysis of data from the 21,105 patients with AF enrolled into ENGAGE AF-TIMI 48, a randomized trial comparing two once-daily regimens of edoxaban (high- and low-dose) with warfarin for the prevention of stroke and systemic embolism. Of the 1,016 patients who met the primary endpoint, 67 (6.6%) had a systemic embolic event (SEE) of which 13% were fatal. Risk factors for systemic embolism versus stroke include age (78 versus 74 years; P=0.005), permanent atrial fibrillation (72% versus 54%; P=0.009), and creatinine clearance ≤ 50 ...
TL;DR: A 58-year-old man, JB, schedules a visit with his primary care physician to explore what he could do to prevent a heart attack or stroke, prompted by his best friend having a heart heart attack and the recollection that his father suffered a massive heart attack at age 59.
Abstract: A 58-year-old man, JB, schedules a visit with his primary care physician to explore what he could do to prevent a heart attack or stroke. He previously considered himself in good health and is not aware of any medical problems or symptoms. His visit is prompted by his best friend having a heart attack and the recollection that his father suffered a massive heart attack at age 59.
JB continues to smoke ≈10 cigarettes a day. He plays an occasional game of pick-up basketball with friends but has a sedentary job. Over the past 20 years, he acknowledges that he has accumulated ≈25 pounds of excess weight. JB cautions his physician that he does not want to take a lot of pills, but is not clear how best to improve his chances of avoiding his father’s fate.
On physical examination, JB’s weight is 230 pounds, height 72 inches, corresponding to a body mass index of 31.2 kg/m2, classified as obese. His blood pressure is 160/95 mm Hg, heart rate 78 beat/min and regular. Apart from his truncal obesity, the remainder of his physical examination is normal. His physician orders blood work, a cholesterol panel, and a blood sugar. After the results are available, he begins a discussion with JB.
Approximately every 34 seconds, someone in the US has a heart attack. Research has shown that there are major risk factors which significantly increase the risk of angina pectoris, heart attack, stroke, and sudden cardiac death—all part of the cardiovascular disease (CVD) spectrum. The modifiable risk factors—factors that can be influenced by healthy behaviors—include hypertension, smoking, elevated blood cholesterol (lipids), and diabetes mellitus. The more risk factors a person has, the greater the chances of developing some form of CVD. Also, the greater the level of each risk factor, …