Ising model partition-function computation as a weighted counting problem.

While the Ising model is most often used to understand physical phenomena, its natural connection to combinatorial reasoning also makes it one of the best models to probe complex systems in science and engineering. We bring a computational lens to the study of Ising models, where our computer-science perspective is twofold: On the one hand, we show that partition function computation (#Ising) can be reduced to weighted model counting (WMC). This enables us to take off-the-shelf model counters and apply them to #Ising. We show that one model counter (TensorOrder) outperforms state-of-the-art tools for #Ising on midsize and topologically unstructured instances, suggesting the tool would be a useful addition to a portfolio of partition function solvers. On the other hand, we consider the computational complexity of #Ising and relate it to the logic-based counting of constraint-satisfaction problems or #CSP. We show that known dichotomy results for #CSP give an easy proof of the hardness of #Ising and provide intuition on where the difficulty of #Ising comes from.

[EFFICACY, PHARMACOKINETICS, PHARMACODYNAMICS, AND SAFETY OF INTRAVENOUS C1 INHIBITOR FOR LONG-TERM PROPHYLAXIS AND TREATMENT OF BREAKTHROUGH ATTACKS IN JAPANESE SUBJECTS WITH HEREDITARY ANGIOEDEMA: A PHASE 3 OPEN-LABEL STUDY].

BACKGROUND: Hereditary angioedema (HAE) is associated with recurrent, painful, and potentially lifethreatening attacks characterized by swelling of subcutaneous or submucosal tissues. PURPOSE: To investigate the efficacy, safety, pharmacokinetics, and pharmacodynamics of repeat-use C1 inhibitor (C1-INH) replacement therapy for long-term prophylaxis and treatment of breakthrough attacks in the management of Japanese patients with HAE type I or II. METHODS: An open-label, single-arm, Phase 3 study was conducted in Japanese patients with HAE (NCT02865720). For patients 6 years of age or older, 1000U were administered biweekly (by a healthcare professional or self-administered) via intravenous infusion. RESULTS: In 8 enrolled patients, the mean number of attacks normalized per month was lower during C1-INH treatment than during the 3 months prior (1.826 vs. 3.375). Clinically meaningful mean change from baseline in the angioedema-quality of life (AE-QoL) total score was shown during treatment with C1-INH. Pharmacokinetic data showed markedly higher and enduring post-baseline plasma levels of C1-INH functional activity and C1-INH antigen concentration, starting from 0.5h after first dose of C1-INH and lasting up to 72 hours. C1-INH was well tolerated with no new safety signals identified in this population of Japanese patients with HAE. CONCLUSION: C1-INH was effective for long-term prophylaxis and treatment of breakthrough attacks with favourable safety profile in Japanese patients with HAE.

Long-term safety outcomes of prekallikrein (Fletcher factor) deficiency: A systematic literature review of case reports.

Background: Hereditary prekallikrein (Fletcher factor) deficiency is a rare condition characterized by a prolonged activated partial thromboplastin time. Inhibitors of plasma kallikrein have recently been approved for prophylaxis of hereditary angioedema and are under investigation for use in other indications. Objective: We attempted to conservatively assess the impact of long-term inhibition of this pathway by reviewing reported comorbidities in patients with hereditary prekallikrein deficiency. Methods: We searched several medical literature databases for publications that reported data from patients with hereditary prekallikrein deficiency (<10% of normal and/or shortening of activated partial thromboplastin time on increased incubation time). Data reporting of cardiovascular, bleeding, and autoimmune-related diseases were extracted. Results: Of 1966 publications screened, 45 publications (which represented 53 patients with prekallikrein deficiency) were included. Among 53 identified patients with prekallikrein deficiency, 25 were explicitly defined as asymptomatic, with no comorbidities mentioned in another three cases. Another 16 of the 53 patients were described as having undergone surgery or dental extractions with no complications. Cardiovascular comorbidities were reported in 19 patients, mainly hypertension (9 patients) and cerebrovascular ischemia or stroke (5 patients). Excessive bleeding episodes after surgery were reported in four patients. Autoimmune-related diseases were reported for three patients (two with Graves disease and one with systemic lupus erythematosus). Conclusion: This review identified patients with hereditary prekallikrein deficiency who reported a spectrum of health outcomes from asymptomatic to infrequent reports of cardiovascular, bleeding, and autoimmune comorbidities. The majority of the reports did not indicate any association between prekallikrein deficiency and comorbidities; however, additional observation is required to confirm the long-term safety of plasma kallikrein inhibition.

Efficacy, pharmacokinetics, and safety of icatibant for the treatment of Japanese patients with an acute attack of hereditary angioedema: A phase 3 open-label study.

BACKGROUND: Hereditary angioedema (HAE) is a genetic disease characterized by recurrent swelling episodes affecting the skin, gastrointestinal mucosa, and upper respiratory tract. METHODS: A phase 3, single-arm, open-label study was performed to evaluate a selective bradykinin B2 receptor antagonist, icatibant, for the treatment of acute attacks in Japanese patients with HAE Type I or II. After the onset of an acute attack, icatibant 30 mg was administered by the patient or a healthcare professional via subcutaneous injection in the abdomen. RESULTS: Eight patients who had an attack affecting the skin (n = 4), abdomen (n = 3), or larynx (n = 1) were treated with icatibant (3 of the injections were self-administered). The median time to onset of symptom relief was 1.75 h (95% confidence interval, 1.00-2.50), and all patients had symptom relief within 5 h after administration. The time to maximum plasma concentration of icatibant was 1.79 h, and the maximum plasma concentration was 405 ng/ml. Seven patients experienced an injection site reaction, and 3 patients had adverse events (2 patients had a worsening or repeat HAE attack 29.0 and 18.3 h after icatibant administration, respectively, and 1 had headache). CONCLUSIONS: Although the number of patients is small, the efficacy and tolerability of icatibant for acute attacks were demonstrated in Japanese patients with HAE, regardless of self-administration or administration by healthcare professional.

Long-term safety outcomes of prekillikrein (Fletcher factor) deficiency: A systematic literature review of case reports.

BACKGROUND: Hereditary prekallikrein (Fletcher factor) deficiency is a rare condition characterized by a prolonged activated partial thromboplastin time. Inhibitors of plasma kallikrein have recently been approved for prophylaxis of hereditary angioedema and are under investigation for use in other indications. OBJECTIVE: We attempted to conservatively assess the impact of long-term inhibition of this pathway by reviewing reportedcomorbidities in patients with hereditary prekallikrein deficiency. METHODS: We searched several medical literature databases for publications that reported data from patients with hereditaryprekallikrein deficiency (<10% of normal and/or shortening of activated partial thromboplastin time on increased incubationtime). Data reporting of cardiovascular, bleeding, and autoimmune-related diseases were extracted. RESULTS: Of 1966 publications screened, 45 publications (which represented 53 patients with prekallikrein deficiency) wereincluded. Among 53 identified patients with prekallikrein deficiency, 25 were explicitly defined as asymptomatic, with no comorbidities mentioned in another three cases. Another 16 of the 53 patients were described as having undergone surgery or dental extractions with no complications. Cardiovascular comorbidities were reported in 19 patients, mainly hypertension (9 patients) and cerebrovascular ischemia or stroke (5 patients). Excessive bleeding episodes after surgery were reported in four patients. Autoimmune-related diseases were reported for three patients (two with Graves disease and onewith systemic lupus erythematosus). CONCLUSION: This review identified patients with hereditary prekallikrein deficiency who reported a spectrum of health outcomes from asymptomatic to infrequent reports of cardiovascular, bleeding, and autoimmune comorbidities. The majority of the reports did not indicate any association between prekallikrein deficiency and comorbidities; however, additional observation is required to confirm the long-term safety of plasma kallikrein inhibition.

A randomized trial of human C1 inhibitor prophylaxis in children with hereditary angioedema.

BACKGROUND: Patients with hereditary angioedema with C1 inhibitor deficiency or dysfunction have burdensome recurrent angioedema attacks. The safety, efficacy, and health-related quality of life (HRQoL) outcomes of C1 inhibitor (C1-INH) prophylaxis (intravenously administered) in patients aged 6-11 years were investigated. METHODS: Eligible patients were enrolled in a randomized, single-blind, crossover, phase 3 trial. After a 12-week baseline observation period (BOP), patients received 500 or 1000 U C1-INH, twice weekly, for 12 weeks before crossing over to the alternate dose for 12 weeks. The primary efficacy end-point was the monthly normalized number of angioedema attacks (NNA). HRQoL was assessed using the EuroQoL 5-dimensional descriptive system youth version and visual analog scale (EQ-VAS). RESULTS: Twelve randomized patients had a median (range) age of 10.0 (7-11) years. Mean (SD) percentage reduction in monthly NNA from BOP was 71.1% (27.1%) with 500 U and 84.5% (20.0%) with 1000 U C1-INH. Mean (SD) within-patient difference (-0.4 [0.58]) for monthly NNA with both doses was significant (P = 0.035 [90% CI, -0.706 to -0.102]). Cumulative attack severity, cumulative daily severity, and number of acute attacks treated were reduced. No serious adverse events or discontinuations occurred. Mean EQ-VAS change from BOP to week 9 of treatment (500 U C1-INH, 10.4; 1000 U C1-INH, 21.6) was greater than the minimal important difference, indicating a meaningful HRQoL change. CONCLUSIONS: C1-INH prophylaxis was effective, safe, and well tolerated in children aged 6-11 years experiencing recurrent angioedema attacks. A post hoc analysis indicated a meaningful improvement in HRQoL with C1-INH. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02052141.

Fixed-Dose Subcutaneous C1-Inhibitor Liquid for Prophylactic Treatment of C1-INH-HAE: SAHARA Randomized Study.

BACKGROUND: Hereditary angioedema (HAE) with C1 inhibitor deficiency (C1-INH) is characterized by swelling of subcutaneous and/or submucosal tissues. OBJECTIVE: To evaluate efficacy/safety of fixed-dose subcutaneous plasma-derived C1-INH (pdC1-INH) liquid for HAE attack prevention (NCT02584959). METHODS: Eligible patients were ≥12 years with ≥2 monthly attacks prescreening or pre-long-term prophylaxis. In a partial crossover design, 80% of patients were randomized to placebo or pdC1-INH liquid for 14 weeks and crossed over from active to placebo or vice versa for another 14 weeks. The remainder were randomized to pdC1-INH liquid for 28 weeks. The primary efficacy endpoint was normalized number of attacks (NNA) versus placebo. Key additional endpoints were the proportion of patients achieving NNA reduction ≥50%, attack severity, number of attack-free days, and safety. RESULTS: Seventy-five patients were randomized and 58 (77%) completed the study. Mean age 41 years; 88% HAE type I. Least-squares means of NNA were reduced from 3.9 with placebo to 1.6 with pdC1-INH (from day 1; P < .0001). Most patients had ≥50% NNA reduction with pdC1-INH (from day 1, 78%). A total of 8.8% of placebo-treated patients were attack-free and 5.3%, 22.8%, and 63.2% had mild, moderate, and severe attacks, respectively; 37.5% of pdC1-INH-treated patients were attack-free and 8.9%, 26.8%, and 26.8% had mild, moderate, and severe attacks, respectively. Treatment-emergent adverse event rates were similar between groups (52% vs 56% for pdC1-INH crossover vs placebo, respectively). CONCLUSIONS: Fixed-dose subcutaneous pdC1-INH liquid was superior to placebo in preventing HAE attacks and demonstrated a favorable safety profile.

[EFFICACY, PHARMACOKINETICS, AND SAFETY OF ICATIBANT FOR THE TREATMENT OF JAPANESE PATIENTS WITH AN ACUTE ATTACK OF HEREDITARY ANGIOEDEMA: A PHASE 3 OPEN-LABEL STUDY].

BACKGROUND: Hereditary angioedema (HAE) is characterized by paroxysmal edema of the skin, gastrointestinal mucosa, and upper respiratory tract. PURPOSE: This study investigated icatibant, a selective bradykinin B2 receptor antagonist, as treatment for Japanese patients with an acute HAE attack. METHODS: This was an open-label, single-arm, Phase 3 study of Japanese adults with HAE type I or II. Icatibant (30 mg) was administered (by a healthcare professional [HCP] or self-administered) as a subcutaneous injection in the abdomen. RESULTS: Eight patients (4 cutaneous, 3 abdominal, 1 laryngeal) were treated with icatibant (all single injection; 3 self-administered, 5 HCP-administered). The median time to onset of symptom relief was 1.75 hours (95% confidence interval, 1.00 to 2.50); all patients had onset of relief within 5 hours. The estimated time to maximum icatibant concentration in the circulation was 1.79 hours and the maximum concentration was 405 ng/mL. There were 3 patients who experienced 3 adverse events (2 HAE attacks and 1 headache); 7 patients experienced an injection site reaction. CONCLUSION: Although our study was limited by the small number of patients, we found that icatibant was an effective and well-tolerated treatment for Japanese patients with acute HAE attacks, regardless of whether it was administered by a HCP or self-administered.

Hemoglobin levels and blood transfusion in patients with sepsis in Internal Medicine Departments.

BACKGROUND: Acute reduction in hemoglobin levels is frequently seen during sepsis. Previous studies have focused on the management of anemia in patients with septic shock admitted to intensive care units (ICU's), including aggressive blood transfusion aiming to enhance tissue oxygenation. AIM: To study the changes in hemoglobin concentrations during the first week of sepsis in the setting of Internal Medicine (IM) units, and their correlation to survival. DESIGN: Observational prospective study. METHODS: We recorded hemoglobin values upon admission and throughout the first week of hospital stay in a consecutive cohort of septic patients admitted to IM units at a community hospital, the patients were enrolled into a prospective registry. Data on blood transfusions was also collected, we examined the correlation between hemoglobin concentrations during the first week of sepsis and survival, the effect of blood transfusion was also assessed. RESULTS: Eight hundred and fifteen patients (815) with sepsis were enrolled between February 2008 to January 2009. More than 20 % of them had hemoglobin levels less than 10g/dL on admission, a rate that was doubled during the first week of sepsis. Overall, 68 (8.3 %) received blood transfusions, 14 of them (20.6 %) due to bleeding. Typically, blood transfusion was given to older patients with a higher rate of malignancy and lower hemoglobin levels. While hemoglobin concentration on admission had strong correlation with in-hospital mortality (O.R-0.83 [95 % C.I. 0.74-0.92], blood transfusion was not found to be an independent predicting factor for mortality. CONCLUSION: Anemia is very common in sepsis. While hemoglobin level on admission exhibit independent correlation with survival, blood transfusion do not.

The accuracy of clinical prediction of prognosis for patients admitted with sepsis to internal medicine departments.

INTRODUCTION: Prognosis estimation offered by physicians for patients inflicted by sepsis on their admission to Internal Medicine (IM) departments is considered a challenge. Early prognosis estimation is critical and determines the intensity of treatment offered. The accuracy of prognosis estimation made by physicians has previously been investigated mainly among intensive care physicians and oncologists. OBJECTIVE: To ascertain the accuracy of prognosis prediction made by internists for septic patients on admission to IM departments. METHODS: Physicians were asked to estimate the prognosis of every patient identified to have sepsis on admission. Their intuitive assessment of prognosis was incorporated into the patients' electronic medical record. Survival follow-up was recorded until death or for at least 2 years. Later we compared survival with physicians' prognosis estimations. RESULTS: Prognosis estimation was recorded for 1,073 consecutive septic patients admitted throughout the years 2008-2009 to IM departments. The mean age of patients was 74.7 ± 16.1 years. A total of 42.4% were suspected to have pneumonia, and 65.4% died during a mean follow-up time of 661.1 ± 612.3 days. Almost half of the patients classified to have good prognosis survived compared to 14.9% and 4.9% of those with intermediate and bad prognosis estimation, respectively (P < 0.001). CONCLUSION: Internists can discriminate well between septic patients with good, intermediate, and bad prognosis.

Drug target optimization in chronic myeloid leukemia using innovative computational platform.

Chronic Myeloid Leukemia (CML) represents a paradigm for the wider cancer field. Despite the fact that tyrosine kinase inhibitors have established targeted molecular therapy in CML, patients often face the risk of developing drug resistance, caused by mutations and/or activation of alternative cellular pathways. To optimize drug development, one needs to systematically test all possible combinations of drug targets within the genetic network that regulates the disease. The BioModelAnalyzer (BMA) is a user-friendly computational tool that allows us to do exactly that. We used BMA to build a CML network-model composed of 54 nodes linked by 104 interactions that encapsulates experimental data collected from 160 publications. While previous studies were limited by their focus on a single pathway or cellular process, our executable model allowed us to probe dynamic interactions between multiple pathways and cellular outcomes, suggest new combinatorial therapeutic targets, and highlight previously unexplored sensitivities to Interleukin-3.

Pharmacogenomic interaction between the Haptoglobin genotype and vitamin E on atherosclerotic plaque progression and stability.

OBJECTIVE: Homozygosity for a 1.7 kb intragenic duplication of the Haptoglobin (Hp) gene (Hp 2-2 genotype), present in 36% of the population, has been associated with a 2-3 fold increased incidence of atherothrombosis in individuals with Diabetes (DM) in 10 longitudinal studies compared to DM individuals not homozygous for this duplication (Hp 1-1/2-1). The increased CVD risk associated with the Hp 2-2 genotype has been shown to be prevented with vitamin E supplementation in man. We sought to determine if there was an interaction between the Hp genotype and vitamin E on atherosclerotic plaque growth and stability in a transgenic model of the Hp polymorphism. METHODS AND RESULTS: Brachiocephalic artery atherosclerotic plaque volume was serially assessed by high resolution ultrasound in 28 Hp 1-1 and 26 Hp 2-2 mice in a C57Bl/6 ApoE(-/-) background. Hp 2-2 mice had more rapid plaque growth and an increased incidence of plaque hemorrhage and rupture. Vitamin E significantly reduced plaque growth in Hp 2-2 but not in Hp 1-1 mice with a significant pharmacogenomic interaction between the Hp genotype and vitamin E on plaque growth. CONCLUSIONS: These results may help explain why vitamin E supplementation in man can prevent CVD in Hp 2-2 DM but not in non Hp 2-2 DM individuals.

Variability in freedom from loss of primary patency results in trials assessing stent implantation in the superficial femoral artery.

BACKGROUND: Primary patency (PP) in trials assessing superficial femoral artery (SFA) stenting is defined as a combination of vessel patency assessed by duplex ultrasound (DUS) at the 12-month follow-up exam and freedom from revascularization of the index vessel through 12 months of follow-up. Loss of PP is thus more likely to be identified during the mandated DUS assessment. Moreover, DUS is performed within a prespecified allowed window of time for the visit that exceeds 12 months (typically by 30 days). Therefore, the time frame for detecting patency with DUS exceeds the time frame in which revascularization is captured. Survival analyses are often applied to present estimates of freedom from loss of PP, but there are no clear guidelines as to the correct method for presenting these analyses in reports from clinical trials. We aimed to analyze the implications of applying different methods in assessing freedom from loss of PP in studies assessing stenting for diseased SFA. METHODS: Data were simulated based on existing available results from SFA bare-metal nitinol stent trials published between 2009 and 2013 and summarized in a previous analysis (STROLL, SUPERB, RESILIENT, DURABILITY I, DURABILTY II, COMPLETE SFA). Six different approaches to Kaplan Meier (KM) analyses were applied based on entry criteria into and time frame of the KM model. RESULTS: Six KM estimates of PP were generated for each of the 10,000 simulated datasets. The average exact PP rate was 70.6%, while the average estimated KM rates using the six different methods ranged between 68.0% and 81.9%. CONCLUSION: KM estimates of PP vary substantially according to the methods employed. These may lead to misrepresentation of results from clinical trials. The development of a unified approach is advocated.

Predictors of recurrent events in patients with cryptogenic stroke and patent foramen ovale within the CLOSURE I (Evaluation of the STARFlex Septal Closure System in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale) trial.

OBJECTIVES: This study sought to identify predictors of recurrent ischemic neurologic events within the CLOSURE I (Evaluation of the STARFlex Septal Closure System in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale) trial. BACKGROUND: The CLOSURE I trial found that transcatheter patent foramen ovale (PFO) closure using the STARFlex device was not superior to medical therapy in patients with cryptogenic stroke or transient ischemic attack (TIA) and PFO. METHODS: The CLOSURE I trial is a multicenter, randomized trial of transcatheter PFO closure compared with medical therapy in patients who presented with cryptogenic stroke or TIA and had a PFO. We identified clinical predictors of recurrent ischemic stroke or TIA during 2 years of follow-up using Cox proportional hazards regression within the pooled intention-to-treat cohort. RESULTS: In 909 patients, the incidence of recurrent events was 5.7% with 25 patients suffering a recurrent stroke and 30 a TIA. Patients who had a recurrent event had higher body mass index (30.2 ± 6.2 vs. 28.3 ± 5.8%; p = 0.03) and more frequently had diabetes (19.2% vs. 7.1%; p = 0.0016), hypertension (46.2% vs. 30.1%; p = 0.015), and ischemic heart disease (3.8% vs. 0.9%; p = 0.05). Diabetes (hazard ratio [HR]: 3.39; 95% confidence interval [CI]: 1.69 to 6.84; p = 0.0007), index TIA (HR vs. stroke: 2.13; 95% CI: 1.20 to 3.80; p = 0.01), and the detection of atrial fibrillation after study enrollment (HR: 4.85; 95% CI: 2.05 to 11.47; p = 0.0003) independently predicted recurrent ischemic neurologic events. Recurrent neurologic events were more frequent in subjects with RoPE (Risk of Paradoxical Embolism) score ≤5 than those with >5 (14.5% vs. 4.2%; p < 0.0001). CONCLUSIONS: These findings suggest an alternative etiology to paradoxical embolism was frequently responsible for recurrent events within the CLOSURE I trial. (Evaluation of the STARFlex Septal Closure System in Patients With a Stroke or TIA Due to the Possible Passage of a Clot of Unknown Origin Through a Patent Foramen Ovale (PFO) [CLOSURE I]; NCT00201461).

Usefulness of postmarket studies to evaluate long-term safety of coronary eluting stents (from the ENDEAVOR and PROTECT Programs).

Differences in enrollment criteria and protocol requirements are believed to affect patient representation and outcomes from premarket and postmarket surveillance (PMS) trials. These differences have not been assessed in studies evaluating coronary stenting. We aimed to assess differences in clinical profile and long-term outcomes in patients enrolled into premarket versus PMS trials assessing the Endeavor zotarolimus-eluting stent (E-ZES). We pooled patient-level data for 2,132 and 4,357 E-ZES-treated subjects enrolled into the ENDEAVOR program (premarket) and Patient Related OuTcomes with Endeavor versus Cypher stenting Trial (PMS), respectively. Follow-up data were available through 3 years. Baseline characteristics and outcomes of patients enrolled in the 2 groups were compared. Propensity score-adjusted Cox proportional hazards models were used to assess the effect of differences in baseline characteristics. We also adjusted for protocol-mandated repeat angiography to account for differences in follow-up requirements. Despite significant differences in baseline characteristics, the unadjusted 3-year rates of major adverse cardiac events, major adverse cardiac and cerebrovascular events, and target vessel failure were similar (premarket vs PMS: 11.9% vs 12.7%, p = 0.369; 12.7% vs 13.9%, p = 0.191; and 13.8% vs 13.4%, p = 0.667, respectively). However, PMS trials had significantly higher rates of myocardial infarctions (p = 0.005) and definite or probable stent thrombosis (p = 0.016). After propensity score adjustment, myocardial infarction rates remained significantly different (hazard ratio 0.53, 95% confidence interval 0.30 to 0.91). To conclude, premarket and PMS trials assessing E-ZES implantation enrolled different patients. PMS trials were shown to be essential for the detection of safety signals.

Evolving antithrombotic strategies in patients with atrial fibrillation undergoing percutaneous coronary intervention: results from a survey among US cardiologists.

BACKGROUND: Many patients treated with oral anticoagulants for atrial fibrillation undergo percutaneous stent implantation, where dual antiplatelet therapy (DAPT) is also recommended. The current evidence to support triple oral antithrombotic therapy (TOAT) in these patients is limited, and new strategies are being discussed to optimize outcomes. HYPOTHESIS: There will be variation in antithrombotic strategies in patients with atrial fibrillation needing stenting. METHODS: We surveyed US-based cardiologists serving as clinical investigators in academic sites and posted an online "question of the month" on cardiosource.org. RESULTS: Seventy-five (10.7%) responses were received to the email survey and 119 to the online question. Bare-metal stenting (BMS) was a priori preferred over drug-eluting stenting (DES) for 50.6% of patients. Only 8.8% of the responders chose newer anticoagulants in addition to DAPT as the preferred oral anticoagulant. For duration of TOAT, 79.4% of physicians recommended stopping DAPT at 1 month when BMS was used in patients presenting without acute coronary syndrome (ACS) vs 57.4% in patients with ACS. In patients implanted with a DES, 73.5% and 76.5% preferred stopping DAPT at 6 to 12 months (no ACS vs ACS, respectively). When asked which of the 2 antiplatelet agents they would recommend stopping after the above durations, 50% chose to quit aspirin. CONCLUSIONS: The survey highlights an interest in the new strategy of dropping aspirin, but the lack of concrete evidence triggers undesired diversity in clinical approaches. High-quality data on the efficacy and safety of such interventions are needed to further consolidate these approaches.

Risk assessment to predict arterial and venous events in patients undergoing percutaneous coronary intervention.

Atherosclerosis and venous thromboembolism (VTE) share common risk factors. We set to assess the strength of the association between atherosclerosis risk factors and disease manifestation, and VTE, in patients with coronary artery disease undergoing percutaneous coronary intervention. We pooled data from 6 global randomized controlled trials assessing coronary stenting (ENDEAVOR and SIRIUS programs), developed separate risk scores to predict major adverse cardiac and cerebrovascular events (MACCEs: cardiac death, myocardial infarction, and stroke) and VTE, and compared their performance. The 5-year rates of MACCE and VTE were 10.8% and 2.04%, respectively. Selected predictors for MACCE performed equally well in predicting VTE (area under the receiver-operating characteristic curve [AUC] 0.651 vs 0.672), and selected predictors for VTE performed equally well in predicting MACCE (AUC 0.699 vs 0.620). Ejection fraction and age were associated with both MACCE and VTE. These findings support the concept of overlapping pathophysiology of VTE and atherothrombosis.

Safety and efficacy metrics for primary nitinol stenting in femoropopliteal occlusive disease: a meta-analysis and critical examination of current methodologies.

BACKGROUND: The efficacy and safety of primary stenting for superficial femoral artery (SFA) disease have been benchmarked against historically derived performance goals. However, contemporary evidence evaluating SFA stenting is accumulating. The objective of this systematic review and meta-analysis was to quantitatively assess outcomes after primary SFA stenting with nitinol stents in contemporary practice, to compare these rates with commonly used efficacy and safety goals, and to discuss the clinical and regulatory implications of these findings. METHODS AND RESULTS: We searched MEDLINE, the US Food and Drug Administration (FDA) website, reference lists of qualifying articles, and conference proceedings until October 2012. Studies prospectively assessing primary nitinol stenting for diseased SFA were sought. Data from 11 prospective clinical trials were included. The twelve-month primary patency (PP) rate was reported in five trials. The meta-analytic 12-month PP rate was 71.6% (95% confidence interval [CI] 66.4-76.7%). The meta-analytic rate of 30-day freedom from a composite of death, target limb amputation, and reintervention was 99.9% (95% CI 100.0-90.0%). CONCLUSION: Contemporary nitinol-based bare-metal stents performed well in controlled settings. Occurrence of the 1-month composite safety endpoint was extremely uncommon.