Joseph S. Rossi

Improvement in hyponatremia during hospitalization for worsening heart failure is associated with improved outcomes: insights from the Acute and Chronic Therapeutic Impact of a Vasopressin Antagonist in Chronic Heart Failure (ACTIV in CHF) trial

Background: Hyponatremia predicts poor outcome in patients with acute heart failure syndromes. This study evaluated the relationship between baseline serum sodium, change in serum sodium, and 60‐day mortality in hospitalized heart failure patients. Methods: A post‐hoc analysis of the ACTIV in CHF trial was performed. ACTIV in CHF randomized 319 patients hospitalized for worsening heart failure to placebo or one of three tolvaptan doses. Cox proportional hazards regression‐analysis was used to explore the relationship between baseline hyponatremia, sodium change during the hospitalization, and 60‐day mortality. Results: Hyponatremia was observed in 69 patients (21.6%). After covariate adjustment, baseline hyponatremia was a statistically significant predictor of 60‐day mortality (P = 0.0016). Follow‐up serum sodium data were available in 68 patients. At hospital discharge, 45 of 68 (66.2%) hyponatremic patients had improvements in serum sodium levels (⩾2 mmol/l). Hyponatremic patients with a serum sodium improvement had a mortality rate of 11.1% at 60 days post discharge, compared with a 21.7% mortality rate in those showing no improvement. After covariate adjustment, change in serum sodium was a statistically significant predictor of 60‐day mortality (HR: 0.736, 95% CI: 0.569–0.952 for each 1‐mmol/l increase in serum sodium from baseline). Conclusions: Serum sodium improvements during hospitalization for heart failure were associated with improved survival at 60 days.

Acute Heart Failure Syndromes in Patients With Coronary Artery Disease : Early Assessment and Treatment

Acute heart failure syndromes (AHFS) have emerged as a leading public health problem worldwide, accounting for a substantial number of hospitalizations and a high utilization of resources. Although in-hospital mortality rates are relatively low, patients with AHFS have very high early after-discharge mortality and rehospitalization rates. The majority of patients admitted with AHFS have coronary artery disease (CAD), which independently has an adverse impact on prognosis. The initial in-hospital and after-discharge management of AHFS may be dependent on clinical presentation: AHFS in patients with underlying CAD or acute coronary syndromes (ACS) complicated by heart failure. In addition, the extent and severity of CAD and the presence of ischemia and/or stunned/hibernating myocardium should be assessed for optimal management. Although the overall management of AHFS with CAD may be similar to that in patients with ACS complicated by heart failure, for which specific guidelines exist, management of the former is less well defined. Prospective studies of the assessment and treatment of CAD in patients with AHFS are urgently needed.

Predictive Value of Dobutamine Stress Echocardiography for Coronary Artery Disease Detection in Liver Transplant Candidates

Patients with obstructive coronary artery disease (CAD) undergoing orthotopic liver transplantation (OLT) are at increased risk of poor outcomes. The accuracy of dobutamine stress echocardiography (DSE) to detect obstructive CAD is not well established in this population. We retrospectively identified patients with end‐stage liver disease who underwent both DSE and coronary angiography as part of risk stratification prior to OLT. One hundred and five patients had both DSE and angiography, of whom 14 had known CAD and 27 failed to reach target heart rate during DSE. Among the remaining 64 patients (45 men; average age 61 ± 8 years) DSE had a low sensitivity (13%), high specificity (85%), low positive predictive value (PPV) (22%) and intermediate negative predictive value (NPV) (75%) for obstructive CAD. DSE as a screening test for obstructive CAD in OLT candidates has a poor sensitivity. The frequent chronotropic incompetence and low sensitivity in patients who achieve target heart rate, even in those with multiple cardiovascular disease risk factors, suggest that alternative or additional methods of risk stratification are necessary.

First Clinical Application of an Actively Reversible Direct Factor IXa Inhibitor as an Anticoagulation Strategy in Patients Undergoing Percutaneous Coronary Intervention

Background— The ideal anticoagulant should prevent ischemic complications without increasing the risk of bleeding. Controlled anticoagulation is possible with the REG1 system, an RNA aptamer pair comprising the direct factor IXa inhibitor RB006 and its active control agent RB007. Methods and Results— This phase 2a study included a roll-in group (n=2) treated with REG1 plus glycoprotein IIb/IIIa inhibitors followed by 2 groups randomized 5:1 to REG1 or unfractionated heparin. In group 1 (n=12), RB006 was partially reversed with RB007 after percutaneous coronary intervention and fully reversed 4 hours later. In group 2 (n=12), RB006 was fully reversed with RB007 immediately after percutaneous coronary intervention. Femoral sheaths were removed after complete reversal. Patients were pretreated with aspirin and clopidogrel. End points included major bleeding within 48 hours; composite of death, myocardial infarction, or urgent target vessel revascularization within 14 days; and pharmacodynamic measures. All cases were successful, with final Thrombolysis in Myocardial Infarction grade 3 flow and no angiographic thrombotic complications. There were 2 ischemic end points in the REG1 group and 1 in the unfractionated heparin group, with 1 major bleed in the unfractionated heparin group. Median activated clotting time values rose from 151 to 236 seconds after RB006. Administration of the partial RB007 dose reversed anticoagulation to an intermediate activated clotting time value of 186 seconds. Complete reversal with RB007 returned the median activated clotting time value to 144 seconds. Both reversal strategies enabled scheduled femoral sheath removal. Conclusions— This study demonstrates the clinical translation of a novel platform of anticoagulation targeting factor IXa and its active reversal to percutaneous coronary intervention and provides the basis for further investigation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00715455.

Influence of coronary artery disease and coronary revascularization status on outcomes in patients with acute heart failure syndromes: A report from OPTIMIZE‐HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure)*

Coronary artery disease (CAD) is frequent among patients hospitalized with acute heart failure syndromes (AHFS).

Ticagrelor versus Genotype-Driven Antiplatelet Therapy for Secondary Prevention after Acute Coronary Syndrome: A Cost-Effectiveness Analysis

BACKGROUND Clopidogrels effectiveness is likely reduced significantly for prevention of thrombotic events after acute coronary syndrome (ACS) in patients exhibiting a decreased ability to metabolize clopidogrel into its active form. A genetic mutation responsible for this reduced effectiveness is detectable by genotyping. Ticagrelor is not dependent on gene-based metabolic activation and demonstrated greater clinical efficacy than clopidogrel in a recent secondary prevention trial. In 2011, clopidogrel will lose its patent protection and likely will be substantially less expensive than ticagrelor. OBJECTIVE To determine the cost-effectiveness of ticagrelor compared with a genotype-driven selection of antiplatelet agents. METHODS A hybrid decision tree/Markov model was used to estimate the 5-year medical costs (in 2009 US

Three-Year Outcomes of Multivessel Revascularization in Very Elderly Acute Coronary Syndrome Patients

) and outcomes for a cohort of ACS patients enrolled in Medicare receiving either genotype-driven or ticagrelor-only treatment. Outcomes included life years and quality-adjusted life years (QALYs) gained. Data comparing the clinical performance of ticagrelor and clopidogrel were derived from the Platelet Inhibition and Patient Outcomes trial. RESULTS The incremental cost-effectiveness ratio (ICER) for universal ticagrelor was

Insights into the inhibition of platelet activation by omega-3 polyunsaturated fatty acids: Beyond aspirin and clopidogrel

10,059 per QALY compared to genotype-driven treatment, and was most sensitive to the price of ticagrelor and the hazard ratio for death for ticagrelor compared with clopidogrel. The ICER remained below

Pharmacological treatment of chronic heart failure

50,000 per QALY until a monthly ticagrelor price of

Bivalirudin versus Unfractionated Heparin during Percutaneous Coronary Intervention in Patients with Non‐ST‐Segment Elevation Acute Coronary Syndrome Initially Treated with Fondaparinux: Results from an International, Multicenter, Randomized Pilot Study (SWITCH III)

693 or a 0.93 hazard ratio for death for ticagrelor relative to clopidogrel. In probabilistic analyses, universal ticagrelor was below