Gerald Chi

Effect of intensive versus standard blood pressure control on major adverse cardiac events and serious adverse events: A bivariate analysis of randomized controlled trials.

ABSTRACT Background: Intensive blood pressure (BP) lowering may offer protective effects against major adverse cardiac event (MACE) but is also associated with a greater risk of a serious adverse event (SAE). The risk-benefit profile of intensive versus standard BP control has not been comprehensively assessed. Methods: Four studies were identified from a systematic literature search for randomized controlled trials comparing intensive versus standard BP lowering that reported both MACE and SAE endpoints. A previously described statistical approach was applied to characterize the efficacy-safety tradeoff of BP control. The bivariate outcome was computed to quantitatively assess the net clinical benefit (NCB) of intensive BP lowering as compared to standard treatment, with positive values indicating increased risks and negative values indicating decreased risks. Results: Data from the SPRINT trial demonstrated that intensive strategy was superior in MACE but inferior in SAE, thereby eroding the NCB (bivariate outcome: 0.33% [−0.50% to 1.21%]). Intensive strategy from the SPS3 trial fulfilled non-inferiority in both MACE and SAE but did not reach a favorable NCB (−1.31% [−2.25% to 0.01%]). The ACCORD trial suggested that intensive strategy was non-inferior in MACE but inferior in SAE (−0.19% [−0.79% to 1.37%]). Results from the VALISH trial were inconclusive for SAE but suggested non-inferiority in MACE (−1.19% [−3.24% to 0.68%]). Conclusions: Compared to the standard blood pressure target, pooled data from randomized controlled trials suggest that intensive strategy did not achieve a net clinical benefit when weighing the benefit of MACE reduction against the risk of SAE under the bivariate framework.Abbreviations: Blood pressure (BP), diastolic blood pressure (DBP), major adverse cardiac event (MACE), net clinical benefit (NCB), serious adverse event (SAE), systolic blood pressure (SBP).

Effect of Procedure and Coronary Lesion Characteristics on Clinical Outcomes Among Atrial Fibrillation Patients Undergoing Percutaneous Coronary Intervention: Insights From the PIONEER AF-PCI Trial

OBJECTIVESnThis study sought to assess whether there were significant interactions of procedural access strategies and lesion characteristics with bleeding and ischemic events among atrial fibrillation (AF) patients anticoagulated with rivaroxaban or warfarin following a percutaneous coronary intervention.nnnBACKGROUNDnAmong stented AF patients, the impact of procedural access strategies or lesion characteristics on antithrombotic safety and efficacy outcomes is unclear.nnnMETHODSnIn the PIONEER AF-PCI (An Open-label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention) trial, 2,124 patients were randomized to 3 groups and followed for 12 months: 1) rivaroxaban 15 mg once daily plus a P2Y12 inhibitor (nxa0= 709); 2) rivaroxaban 2.5 mg twice a day plus dual antiplatelet therapy (DAPT) (nxa0= 709); and 3) dose-adjusted warfarin plus DAPT (nxa0= 706). Kaplan-Meier rates of clinically significant bleeding and major adverse cardiovascular events were compared between treatments stratified by subgroups of procedure type and lesion characteristics.nnnRESULTSnCompared with warfarin, both rivaroxaban regimens consistently reduced clinically significant bleeding across subgroups of radial versus femoral arterial access and by vascular closure device use. Treatment effect of rivaroxaban on major adverse cardiovascular events did not vary when stratified by ischemia-driven revascularization, urgency of revascularization, location of culprit artery, presence of bifurcation lesion, presence of thrombus, type, and length of stent or number of stents (interaction p > 0.05 for all subgroups).nnnCONCLUSIONSnAmong stented AF patients requiring long-term oral anticoagulation, there was no effect modification by procedure or lesion characteristics of either clinically significant bleeding or major adverse cardiovascular events. Rivaroxaban-based therapy was superior to warfarin plus DAPT in bleeding outcomes regardless of the type of stent or arterial access during the index coronary revascularization. (A Study Exploring Two Strategies of Rivaroxaban [JNJ39039039; BAY-59-7939] and One of Oral Vitamin K Antagonist in Patients With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention [PIONEER AF-PCI]; NCT01830543).

Association of Anemia with Venous Thromboembolism in Acutely Ill Hospitalized Patients: An APEX Trial Substudy

BACKGROUNDnAnemia is a common finding and independent predictor for adverse outcomes in hospitalized patients with medical illness. It remains unclear whether anemia is a risk factor for venous thromboembolism and whether the presence of anemia can refine risk assessment for prediction of venous thromboembolism, thereby adding incremental utility to a validated model.nnnMETHODSnIn the Acute Medically Ill Venous Thromboembolism Prevention with Extended Duration Betrixaban trial (APEX), 7513 hospitalized medical patients were randomized to receive either betrixaban or standard-of-care enoxaparin for thromboprophylaxis. Baseline hemoglobin concentrations were obtained in 6861 patients, with a follow-up of 77 days. Symptomatic venous thromboembolism events, including symptomatic deep vein thrombosis, pulmonary embolism, and venous thromboembolism-related mortality, were compared between low-hemoglobin and normal-hemoglobin groups (normal range: 12.5-17.0xa0g/dL for males and 11.0-15.5xa0g/dL for females). The relationship between anemia and venous thromboembolism events was assessed by fitting a univariable and multivariable logistic regression model composed of thromboprophylaxis and risk factors. Venous thromboembolism risk refinement by hemoglobin measurement was evaluated in the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) risk assessment model.nnnRESULTSnLow hemoglobin at baseline was associated with a greater risk of symptomatic venous thromboembolism (relative risk [RR]xa01.94 [95% confidence interval, 1.27-2.98]; Pxa0=xa0.002), symptomatic deep vein thrombosis (RRxa02.29 [1.12-4.68]; Pxa0=xa0.019), and nonfatal pulmonary embolism (RRxa02.63 [1.22-5.65]; Pxa0=xa0.010) but not venous thromboembolism-related mortality (RRxa01.47 [0.71-3.04]; Pxa0=xa0.30). After adjusting for thromboprophylaxis, history of previous venous thromboembolism, intensive or coronary unit admission, and D-dimer, low hemoglobin (as a categorical or continuous variable) remained associated with an increased likelihood of venous thromboembolism (adjusted odds ratioxa01.71 [95% confidence interval, 1.09-2.69]; Pxa0=xa0.020). Low hemoglobin also improved risk discrimination and reclassification after inclusion in the IMPROVE model.nnnCONCLUSIONSnAnemia was independently associated with a greater risk of symptomatic venous thromboembolism among acutely ill medical patients despite the provision of thromboprophylaxis. Hemoglobin measurement also improved risk stratification by the IMPROVE venous thromboembolism risk score.

Association of D-dimer Levels with Clinical Event Rates and the Efficacy of Betrixaban versus Enoxaparin in the APEX Trial

Background u2003Elevated D-dimer concentrations are associated with an increased risk of venous thromboembolism (VTE). However, they may also provide prognostic value. The present analysis sought to study the association of D-dimer levels with VTE event rates and the efficacy of betrixaban versus enoxaparin in the APEX trial. Methods u2003Hospitalized acutely medically ill subjects ( n u2009=u20097,513) were randomized in a double-dummy double-blind fashion to either extended-duration oral betrixaban (80u2009mg once daily for 35–42 days) or standard dose subcutaneous enoxaparin (40u2009mg once daily for 10u2009±u20094 days) for venous thromboprophylaxis. D-dimer was assessed using a central core laboratory measurement. Results u2003For every 0.25 µg/mL increase in D-dimer concentration, there was a 2% increase in the relative risk of experiencing the primary efficacy endpoint (asymptomatic deep vein thrombosis [DVT], symptomatic DVT, nonfatal pulmonary embolism, or VTE-related death) in both the betrixaban ( p u2009<u20090.001) and enoxaparin ( p u2009<u20090.001) treatment arms. Among D-dimer-positive (≥ 2u2009×u2009upper limit of normal; corresponding to ≥ 1.00 µg/mL) subjects, extended-duration betrixaban reduced the risk of experiencing the primary efficacy outcome (5.4% [ n u2009=u2009124] vs. 7.6% [ n u2009=u2009170]; odds ratiou2009=u20090.69; 95% confidence interval: 0.55–0.88; absolute risk reductionu2009=u20092.2%, number needed to treatu2009=u200946, p u2009=u20090.003). There was no interaction between D-dimer and the treatment effect ( p int u2009=u20090.53). Conclusion u2003Extended-duration betrixaban was superior to standard-duration enoxaparin, irrespective of D-dimer level at baseline. To prevent one VTE event, 46 D-dimer-positive patients would need to be treated with betrixaban.

Dual Antithrombotic Plus Adjunctive Antiinflammatory Therapy to Improve Cardiovascular Outcome in Atrial Fibrillation Patients with Concurrent Acute Coronary Syndrome: A Triple-Pathway Strategy

The concurrence of atrial fibrillation and acute coronary syndrome poses a conundrum in the antithrombotic management as intensification of anticoagulation or antiplatelet therapy inevitably comes at the price of an increased bleeding risk. Various antithrombotic combinations have been attempted to prevent the recurrent cardiovascular events, however, there has been limited success in effective risk reduction for this high risk population. Given the overarching effect of interleukin 1β-driven inflammation on the arrhythmogenesis, thrombogenesis, and hypercoagulability, we hypothesize that the triple-pathway strategy (i.e., incorporating antiinflammatory therapy into anticoagulant and antiplatelet therapy) would grant incremental cardiovascular benefits for atrial fibrillation patients with coexisting acute coronary syndrome and stent placement.

Eosinophilic inflammation in spontaneous coronary artery dissection: A potential therapeutic target?

Spontaneous coronary artery dissection (SCAD), defined as non-traumatic, non-iatrogenic dissociation of coronary vessel wall resulting from intimal disruption or intramural hemorrhage, represents an important cause of sudden death and myocardial infarction among young or middle-aged women without conventional risk factors for atherosclerosis. On histopathological examination, SCAD is featured by prominent eosinophilic infiltration of the adventitia or periadventitial layer of coronary artery. It has been estimated that approximately 15-30% of SCAD patients experience recurrent episodes of dissection despite medical therapy. Preliminary evidence suggests that injury to the vascular endothelium and myocytes in the arterial wall may be explained by cytotoxic products released from eosinophils in response to inflammatory mediators. In addition, neovascularization of vasa vasorum and dilatation of intimal capillaries may be stimulated by localized eosinophils. Newly formed fragile vasa vasorum may disrupt due to high intraluminal pressure from the interconnected capillary network, leading to the expansion of intramural hemorrhage. It is hypothesized that anti-inflammatory therapy targeting eosinophilic coronary periarteritis would be effective in preventing the recurrence of SCAD by promoting the healing of dissection. The article delineates the biological plausibility, empirical data, and future perspective regarding eosinophilic inflammation as a potential therapeutic target for SCAD.

Comparative Efficacy and Safety of Rivaroxaban-Based Dual-Pathway Antithrombotic Therapy Versus Dual Antiplatelet Therapy: A Pooled Analysis of Contemporary Randomized Controlled Trials

Dual antiplatelet therapy (DAPT) has been the mainstay of antithrombotic management for acute coronary syndrome (ACS). Approximately 5-10% of patients experience recurrent events despite standard treatment, and there is an unmet demand for secondary cardiovascular prevention in the post-ACS setting

Scleral exposure alterations following Le Fort I osteotomy (with and without maxillary impaction) in skeletal class III patients: A before-and-after clinical trial

PURPOSEnExposure of sclera below the iris in natural head positions is aesthetically undesirable. Studies on post-surgical changes in inferior scleral exposure following orthognathic surgery are scarce and mostly retrospective. The aim of this clinical trial is to examine the effect of Le Fort I osteotomy, a procedure for correction of malocclusion and maxillo-mandibular deformities, on the inferior scleral exposure and overall scleral surface area in skeletal class III patients.nnnMATERIALS AND METHODSnThis trial was performed on 40 eyes of 20 skeletal class III patients undergoing Le Fort I osteotomy without impaction (nxa0=xa020 eyes) and with impaction (nxa0=xa020 eyes). Standard true-size frontal photography was performed pre-operatively and post-operatively at 6 months. After measuring the overall eye height and the height of visible inferior sclera, the ratio of inferior sclera to overall eye height (S:E) was calculated three times. Also, overall surface area of the sclera was measured three times. The average of three attempts was considered the main measurement. Changes in the sclera after the surgery and between both methods were compared.nnnRESULTSnThe average age of patients (9 men, 11 women) was 24.5 years. Age and gender were balanced between the two groups (Pxa0>xa00.05). S:E ratios decreased in both groups after surgery (Pxa0<xa00.05, Wilcoxon test). The decrease was greater in the impaction group (Pxa0<xa00.05, Mann-Whitney test). Similar results were observed for overall sclera surface areas.nnnCONCLUSIONnMaxillary advancement, with or without impaction, reduced the inferior scleral exposure and overall scleral surface area. The effect was more pronounced in the impaction group.

Inverse relationship of serum albumin to the risk of venous thromboembolism among acutely ill hospitalized patients: Analysis from the APEX trial

Hypoalbuminemia is a common finding and independent predictor for unfavorable prognosis. The prognostic value of albumin measurement for short‐term VTE prediction in hospitalized patients remains unclear. In the APEX trial (ClinicalTrials.gov identifier: NCT01583218), medical inpatients were randomized to receive either extended‐duration betrixaban or shorter‐duration enoxaparin and followed for 77u2009days. Baseline albumin concentrations were obtained in 7266 subjects with evaluable VTE endpoints. The association of baseline albumin to VTE was assessed, with adjustment for patient characteristics, thromboprophylaxis, and biomarkers for fibrinolysis and inflammation (ie, D‐dimer and C‐reactive protein [CRP]). VTE risk refinement was evaluated by incorporation of albumin to well‐validated risk assessment models. A stepwise increase in the risk of VTE (Pu2009<u2009.0001) was observed with lower levels of albumin. Patients at the bottom albumin quartile (<35u2009g/L) had a two‐fold greater odds for developing VTE compared with the top quartile (≥42u2009g/L) (ORu2009=u20092.119 [95% CI, 1.592‐2.820]; adjusted ORu2009=u20092.079 [1.485‐2.911]). The odds for VTE increased by 1.368 (95% CI, 1.240‐1.509) times per SD decrement of albumin (5.24u2009g/L). Compared with the propensity score‐matched pairs of patients with albumin ≥35u2009g/L, patients with albumin <35u2009g/L had a greater risk of VTE (ORu2009=u20091.623 [1.260‐2.090]; adjusted ORu2009=u20091.658 [1.209‐2.272]). Albumin measurement also refined VTE risk discrimination and reclassification after inclusion in the risk assessment models. In conclusion, acutely ill hospitalized patients with low serum albumin had an increased VTE risk through 77u2009days. VTE risk assessment models for medical inpatients should consider incorporation of baseline albumin measurement.