Gary S. Ledley

Randomized Double-Blind Assessment of the ONSET and OFFSET of the Antiplatelet Effects of Ticagrelor Versus Clopidogrel in Patients With Stable Coronary Artery Disease The ONSET/OFFSET Study

Background— Ticagrelor is the first reversibly binding oral P2Y12 receptor antagonist. This is the first study to compare the onset and offset of platelet inhibition (IPA) with ticagrelor using the PLATO (PLATelet inhibition and patient Outcomes) trial loading dose (180 mg) with a high loading dose (600 mg) of clopidogrel. Methods and Results— In a multicenter, randomized, double-blind study, 123 patients with stable coronary artery disease who were taking aspirin therapy (75 to 100 mg/d) received ticagrelor (180-mg load, 90-mg BID maintenance dose [n=57]), clopidogrel (600-mg load, 75-mg/d maintenance dose [n=54]), or placebo (n=12) for 6 weeks. Greater IPA (20 &mgr;mol/L ADP, final extent) occurred with ticagrelor than with clopidogrel at 0.5, 1, 2, 4, 8, and 24 hours after loading and at 6 weeks (P<0.0001 for all); by 2 hours after loading, a greater proportion of patients achieved >50% IPA (98% versus 31%, P<0.0001) and >70% IPA (90% versus 16%, P<0.0001) in the ticagrelor group than in the clopidogrel group, respectively. A faster offset occurred with ticagrelor than with clopidogrel (4-to-72–hour slope [% IPA/h] −1.04 versus −0.48, P<0.0001). At 24 hours after the last dose, mean IPA was 58% for ticagrelor versus 52% for clopidogrel (P=NS). IPA for ticagrelor on day 3 after the last dose was comparable to clopidogrel at day 5; IPA on day 5 for ticagrelor was similar to clopidogrel on day 7 and did not differ from placebo (P=NS). Conclusions— Ticagrelor achieved more rapid and greater platelet inhibition than high-loading-dose clopidogrel; this was sustained during the maintenance phase and was faster in offset after drug discontinuation. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00528411.

Randomized Double-Blind Assessment of the ONSET and OFFSET of the Antiplatelet Effects of Ticagrelor Versus Clopidogrel in Patients With Stable Coronary Artery Disease Randomized Double-Blind Assessment of the ONSET and OFFSET of the Antiplatelet Effects of Ticagrelor Versus Clopidogrel in Patients With Stable Cornonary Disease: The ONSET/OFFSET Study

Background— Ticagrelor is the first reversibly binding oral P2Y12 receptor antagonist. This is the first study to compare the onset and offset of platelet inhibition (IPA) with ticagrelor using the PLATO (PLATelet inhibition and patient Outcomes) trial loading dose (180 mg) with a high loading dose (600 mg) of clopidogrel. Methods and Results— In a multicenter, randomized, double-blind study, 123 patients with stable coronary artery disease who were taking aspirin therapy (75 to 100 mg/d) received ticagrelor (180-mg load, 90-mg BID maintenance dose [n=57]), clopidogrel (600-mg load, 75-mg/d maintenance dose [n=54]), or placebo (n=12) for 6 weeks. Greater IPA (20 &mgr;mol/L ADP, final extent) occurred with ticagrelor than with clopidogrel at 0.5, 1, 2, 4, 8, and 24 hours after loading and at 6 weeks (P<0.0001 for all); by 2 hours after loading, a greater proportion of patients achieved >50% IPA (98% versus 31%, P<0.0001) and >70% IPA (90% versus 16%, P<0.0001) in the ticagrelor group than in the clopidogrel group, respectively. A faster offset occurred with ticagrelor than with clopidogrel (4-to-72–hour slope [% IPA/h] −1.04 versus −0.48, P<0.0001). At 24 hours after the last dose, mean IPA was 58% for ticagrelor versus 52% for clopidogrel (P=NS). IPA for ticagrelor on day 3 after the last dose was comparable to clopidogrel at day 5; IPA on day 5 for ticagrelor was similar to clopidogrel on day 7 and did not differ from placebo (P=NS). Conclusions— Ticagrelor achieved more rapid and greater platelet inhibition than high-loading-dose clopidogrel; this was sustained during the maintenance phase and was faster in offset after drug discontinuation. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00528411.

Health Resource Variability in the Achievement of Optimal Performance and Clinical Outcome in Ischemic Heart Disease

A disparity between evidence and practice in the management of ischemic heart disease is frequently observed. Guideline adherence and clinical outcomes are influenced by system, provider, and patient factors. Recently, performance improvement measures for cardiovascular disease have gained a lot of popularity worldwide. These measures may facilitate the uptake of evidence-based recommendations and improve patient outcomes. While apparently valid as quality metrics, their impacts on clinical outcomes remain limited and are areas of further research. Several methods for optimizing performance have been instituted and essentially involve three different approaches—improvement in the reporting of data on guideline adherence, providing infrastructure and tools, and providing incentives to improve guideline adherence. Public reporting of quality metrics and “pay-for-performance” are some novel performance improvement tools. The impact of these approaches on patient outcomes will be pivotal in improving cardiovascular outcomes in the future.

A Pilot Study Examining the Initial Effectiveness of a Brief Acceptance-Based Behavior Therapy for Modifying Diet and Physical Activity among Cardiac Patients.

Approximately 90% of cardiac events are attributable to a small number of modifiable behavioral risk factors that, if changed, can greatly decrease morbidity and mortality. However, few at-risk individuals make recommended behavioral changes, including those who receive formal interventions designed to facilitate healthy behavior. Given evidence for the potential of specific psychological factors inherent in acceptance-based behavior therapy (ABBT; that is, intolerance of discomfort, mindfulness, and values clarity) to impact health behavior change, the authors evaluated the feasibility and initial effectiveness of an ABBT pilot program designed to increase adherence to behavioral recommendations among cardiac patients. Participants (N = 16) were enrolled in four, 90-min group sessions focused on developing mindfulness and distress tolerance skills, and strengthening commitment to health-related behavior change. Participants reported high treatment satisfaction and comprehension and made positive changes in diet and physical activity. This was the first evaluation of an ABBT program aimed at increasing heart-healthy behaviors among cardiac patients.

Intervention strategies for multi-vessel disease in patients with ST-segment elevation myocardial infarction: a meta-analysis of randomized trials.

a Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso, TX, USA b St Lukes-Roosevelt Hospital Center of the Mount Sinai Health System, New York, NY, USA c Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA d Cardiac Department, Hospital Universitario de La Princesa, IIS-IP, Universidad Autonoma de Madrid, c/ Diego de Leon 62, Madrid 28006, Madrid, Spain e College of Medicine, University of Cincinnati, 231 Albert Sabine Way, Cincinnati, OH, USA f Drexel University College of Medicine, Philadelphia, PA, USA g Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC, USA

Clinical Utility of Intravascular Ultrasound in the Assessment of Coronary Allograft Vasculopathy: A Review

Coronary artery vasculopathy (CAV) is one of the major factors that limit the long-term survival of heart transplant recipients. It is difficult to diagnose CAV, especially in the early stages. Traditional coronary angiography has been used for the diagnosis of CAV, but this method has limitations. Current literature suggests that intravascular ultrasound (IVUS) is a safe imaging technique that is beneficial for the early diagnosis of CAV; in comparison, IVUS with virtual histology (IVUS-VH) is an even more promising diagnostic utility. Despite its advantages, IVUS is currently not routinely utilized as the primary diagnostic modality for CAV in heart transplant recipients. In this review, we evaluate and summarize the clinical utility of IVUS in the early diagnosis of CAV, including its utility for assessing vessel remodeling, plaque composition, and prognostic value; morphometric analysis; and guiding therapy. After reviewing the relevant published literature, it is our recommendation that the use of IVUS be considered in all post-transplant CAV screening.

Revisiting transthyretin related cardiac amyloidosis: Case report and review of literature

Amyloidosis is a complex group of disorders that can involve many organs and cause their dysfunction. Cardiac involvement indicates worse prognosis and influences treatment strategies. Cardiac amyloidosis is an under-diagnosed entity and high index of clinical suspicion and careful interpretation of basic diagnostic tools such as electrocardiogram and echocardiography is needed for early detection. Congestive heart failure due to restrictive pattern and/or conduction system abnormality, in absence of coronary artery disease should raise suspicion. We present a case of transthyretin related cardiac amyloidosis and discuss the key clinical and diagnostic findings along with review of existing literature regarding its management and outcomes.

Hemodynamics and Heart Failure

Every year in the United States, there are approximately 550,000 newly diagnosed heart failure patients. Five million patients suffer from chronic heart failure. Acute heart failure exacerbation is the leading cause for hospitalization in Medicare patients over the age of 65. A fundamental understanding in the definition, etiology, pathophysiology and hemodynamics has led to advances in treatments.

Bivalirudin Use in the Elderly for Acute Coronary Syndrome

ABSTRACT Introduction: Bivalirudin has been approved for use in acute coronary syndromes as part of the anticoagulation regimen. Elderly patients are at a higher risk for bleeding because of their co morbidities, decreased body mass and their age. Hence, this article reviews the landmark published papers on bivalirudin therapy in this patient population with the goal of understanding the particular benefits and risks. Discussion: Several review articles suggest that the use of bivalirudin alone is associated with lower rates of major bleeding when compared with unfractionated heparin plus glycoprotein IIb/IIIa inhibitor in patients with acute coronary syndrome with invasive strategy planned. These beneficial effects span through the age ranges. Therefore, it is a good option for elderly patients. Decreased bleeding complications lead to better clinical outcomes in the elderly after percutaneous coronary intervention. It also leads to decreased length of stay in the hospital. Keywords: Anticoagulants; elderly; acute coronary syndrome; ST elevation myocardial infarction.