American College of Cardiology 61st Annual Scientific Session and Expo

Cardiology Review® Online, April 2012, Volume 28, Issue 2

American College of Cardiology 61st Annual Scientific Session and Expo

Over 13,000 cardiovascular professionals attended the 2012 American College of Cardiology’s 61st Annual Scientific Session in Chicago from March 24 through March 27, 2012. Each day brought exciting presentations about new research in cardiovascular health. Cardiology Review is zeroing in on 6 presentations from ACC.12: FOCUS-CCTRN, BRIDGE-ACS, EINSTEIN-PE, STAMPEDE, IMMEDIATE, and the ACCF-STS Database Collaboration.

FOCUS-CCTRN: Findings Negative, But They Point to Future Cell Therapy in HF

Treatment of patients with ischemic heart disease with autologous bone marrow mononuclear cells (BMCs) has been shown to be safe and feasible in preliminary studies, but the small number of patients followed did not allow a definitive assessment of efficacy.

FOCUS-CCTRN tested BMC therapy in 92 patients with chronic ischemic heart failure (HF), the largest study to date of this therapy. Patients had coronary artery disease, left ventricular ejection fraction (LVEF) <45%, limiting angina and/or congestive HF, a perfusion defect by single photon emission computed tomography (SPECT), and no revascularization options while receiving guideline-based medical therapy. Patients were randomized to receive bone marrow aspiration and transendocardial injection of 100 million bone marrow cells or placebo.

At 6 months, BMD therapy had no significant effect on the prespecified end points of left ventricular end-systolic volume (LVESV), maximal oxygen consumption,

or reversibility on SPECT. There were also no differences found in any secondary outcomes, including myocardial defect percentage, total defect size, fixed defect size, regional wall motion, and clinical improvement.

However, researchers saw a silver lining in the results of an exploratory analysis that showed significant improvement in LVEF (improved 2.7% in the cell therapy group versus placebo), and an improvement in ejection fraction that correlated with the number of progenitor cells in the bone marrow.

Lead author Emerson C. Perin, MD, PhD, of the Texas Heart Institute in Houston, said the findings may seem negative, but, to the contrary, were very exciting. The results of the study provide evidence for further studies to determine the relationship between the composition and function of bone-marrow product and clinical end points. The study’s results are very important because they have informed cell therapy researchers how to better treat this high-risk patient population, so that they can enter the next generation of stem cell therapy armed with more data.

Perin EC, Willerson JT, Pepine CJ, et al. Effect of transendocardial delivery of autologous bone marrow mononuclear

cells on functional capacity, left ventricular function, and perfusion in chronic heart failure: the FOCUS-CCTRN

trial [published online ahead of print March 24, 2012]. JAMA. 2012;307(16). doi:10.1001/jama.2012.418.

Use of Evidence-Based Therapies Improved by Multifaceted Intervention

Despite evidence establishing the efficacy of therapies such as antiplatelet therapy and anticoagulation for patients with acute coronary syndromes (ACS), as well as for secondary prevention treatments, it has been shown that translating research findings into established medical practice is less than optimal—particularly in low- and middle-income countries, which bear more than 80% of the global burden of cardiovascular disease. Brazilian researchers have shown it is possible to improve

adherence to evidencebased practices with a multifaceted quality improvement (QI) intervention among ACS patients. The Brazilian Intervention to Increase Evidence Usage in Acute Coronary Syndromes (BRIDGE-ACS) randomized 34 public hospitals in Brazil with a total of 1150 ACS patients treated in late 2011. About 80% of the hospitals were teaching hospitals in major urban areas and 41% had 24-hour PCI capabilities; 36% of patients had non-ST-segment elevation myocardial

infarctions (non-STEMIs), 40% presented with STEMI, and almost 24% presented with unstable angina.

Although the in-hospital cardiovascular event rates were 5.5% in the QI group versus 7.0% in the control group, the study was not large enough to show a statistically significant difference in outcomes. However, 67.9% of patients in the QI interventions got all recommended acute interventionscompared with only 49.5% of the controls. Patients in the QI group were also more likely than controls to receive all eligible and discharge medications (50.9% versus 31.9%). BRIDGE-ACS showed that QI initiatives are effective even in challenging settings that are overcrowded and have heavier individual clinical workloads. The QI program used simple components that did not rely on expensive information technology or complex human interventions. Lead author Otávio Berwanger, MD, of the Hospital do Coracão, São Paolo, Brazil, said the interventions remind physicians of what to do when decisions are about to be made, “because the reasons for the gap between the guidelines and what physicians do in practice are complex.” For example, in the QI initiative triage nurses put yellow stickers on charts of patients with chest pain to remind treating physicians to review the checklist of recommended steps for these patients. Patients also wear colored wristbands indicating risk of STEMI. Tasking nurses to be case coordinators was considered one of the most important components of the QI program because the coordinators ensured that evidence-based decisions made at the beginning of patients’ care carried through their entire hospitalization.

This study was funded by the Brazilian Ministry of Health in partnership with the Hospital do Coracão-Programa Hospitals de Excelencia a Servico do SUS. Berwanger O, Guimaraes H, Laranjeira L, et al. Effect of a multifaceted intervention on use of evidence-based therapies in patients with acute coronary syndromes in Brazil: the BRIDGEACS randomized trial. [published online ahead of print March 25, 2012]. JAMA. 2012;307(19). doi:10.1001/ jama.2012.4130.

Rivaroxaban Monotherapy Treats PE With Less Risk of Bleeding

A simple fixed-dose regimen of the oral factor Xa inhibitor rivaroxaban treats pulmonary embolism (PE) as well as injected low-molecular-weight heparin and warfarin does, but halved the risk of major bleeding, particularly in major intracranial hemorrhage and retroperitoneal bleeds, according to results of the EINSTEIN-PE trial. EINSTEIN-PE was a randomized, openlabel, event-driven noninferiority trial of 4832 patients with acute symptomatic PE with or without deep vein thrombosis (DVT)

that compared rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with standard therapy with enoxaparin followed by an adjusted-dose vitamin K antagonist for 3, 6, or 12 months. The trial’s primary efficacy outcome was symptomatic recurrent venous thromboembolism; the principal safety outcome was major or clinically relevant nonmajor bleeding.

Rivaroxaban was noninferior to enoxaparin followed by a vitamin K antagonist (rate of recurrent symptomatic venous thromboembolism, 2.1% versus 1.8%; P = 0.003 for noninferiority), with 50 events in the rivaroxaban group (2.1%) versus 44 in the standard therapy group (1.8%) [hazard ratio (HR), 1.12; 95% confidence interval (CI), 0.75-1.68]. The principal safety outcome occurred in 10.3% of patients in the rivaroxaban group and 11.4% of those in the standard therapy group [HR, 0.90; 95% CI, 0.76-1.07; P = 0.23]. Major bleeding occurred in 26 patients (1.1%) in the rivaroxaban group and 52 patients (2.2%) in the standard therapy group [HR, 0.49; 95% CI,

0.31-0.79; P = 0.003).

“We want to make life easier,” said EINSTEIN-PE lead author Henry R. Büller, MD, of the University of Amsterdam Academic Medical Center, The Netherlands. He noted

that many patients and physicians dislike the monitoring required with warfarin and similar agents. “Having a strategy with a pill and no monitoring is, I believe, a small revolution,” he concluded. He also said that patients aged over 75 years particularly benefited from rivaroxaban with regard to major bleeding.

Rivaroxaban is not currently approved for treatment of DVT or PE; it is approved for DVT prophylaxis after knee or hip replacement surgery and for stroke prevention in patients with AF.

This study was funded by Bayer HealthCare and Janssen Pharmaceuticals. EINSTEIN-PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism [published online ahead of print March 26, 2012]. N Engl J Med. 10.1056/NEJMoa1113572.

Bariatric Surgery Improves Standard Treatment in Obese Type 2 Diabetics

In obese patients with type 2 diabetes, bariatric surgery performed better than traditional medical therapy, independent of weight loss, according to the results of the Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) study.

Dr Philip R. Shauer, MD, of the Bariatric and Metabolic Clinic at Cleveland Clinic, and colleagues enrolled 150 obese patients (body mass index [BMI] = 27-43 kg/m2) with uncontrolled type 2 diabetes and randomly assigned them to medical therapy, Roux-en-Y gastric bypass (RYGB), or sleeve gastrectomy.

Patients’ mean age was 49 years and mean HbA1c was 9.2%.

After 12 months of treatment, the main study outcome of HBA1c <6.0% was met by 12% of the medical-therapy group, 42% of the RYGB group (P = 0.002 versus medical therapy), and 37% of the sleeve gastrectomy group (P = 0.008 versus medical therapy). Glycemic control improved in all 3 groups but was significantly greater in the surgical groups. Weight loss was better in the surgical groups than in the medical therapy group, and the use of medications to lower glucose, lipid, and blood pressure levels decreased significantly after both surgical procedures but increased in patients receiving medical therapy only. Measures of insulin resistance improved

significantly after bariatric surgery.

The authors concluded that bariatric surgery represents a potentially useful strategy for management of uncontrolled diabetes “since it has been shown to eliminate the need for diabetes medications in some patients, and to markedly reduce the need for drug treatment in others.” Further study will be needed to assess how long the results are sustained.

This study was funded by Ethicon Endo-Surgery. Schauer PR, Kashyap SR, Wolski K, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes [published online ahead of print March 26, 2012]. N Engl J Med. 10.1056/NEJMoa1200225.

Glucose-Insulin-Potassium Given by EMS Fails to Show Clinical Benefit

IV administration of glucose-insulin-potassium (GIK) by emergency medical services (EMS) personnel in patients suspected of having an acute coronary syndrome (ACS)

failed to provide clinical benefit when compared with patients who received a glucose placebo, according to results of the IMMEDIATE (Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care) trial. The study was designed so that GIK was administered by paramedics in the out-ofhospital setting, aided by computerized ECG-based decision support, rather than having to wait for a hospital-based diagnosis of MI. IV GIK was given to 411 patients and 460 patients got 5% glucose placebo administered by EMS in the out-of-hospital setting and continued for 12 hours. The primary end point was progression of ACS to MI. In the first hours of a suspected ACS event, there was no significant difference in the rate of progression of MI in the 2 treatment groups (48.7% versus 52.6% in the GIK- and placebo- treated groups, respectively; P = 0.28) and no difference in 30-day mortality rates (4.4% versus 6.1%, respectively; P = 0.27). There was a statistically significant 52% reduction in the composite end point of cardiac arrest or in-hospital mortality (odds ratio, 0.48; P = 0.01). The rate of cardiac arrest or in-hospital mortality was 4.4% in the GIK-treated patients and 8.7% in the placebo arm. Results were similar when researchers examined STEMI patients alone.

In a relatively small cohort of 110 ACS patients who underwent imaging at 30 days, infarct size was reduced in the GIK-treated patients compared with those who had placebo. Lead author Harry P. Selker, MD, MSPH, of Tufts Medical Center in Boston, MA, said it was possible that infarct size may better capture a myocardial preservation effect of GIK in this setting, consistent with the metabolic support model of infarct limitation seen in experimental studies. Further studies of that hypothesis are needed.

Selker HP, Beshansky JR, Sheehan PR, et al. Out-of-hospital administration of intravenous-insulin-potassium in patients with suspected acute coronary syndromes [published online ahead of print March 27, 2012]. JAMA. 2012;307(18). doi:10.1001/jama.2012.426.

Lower Mortality After CABG Than After PCI in ACCF and STS Database

A large observational study of nearly 190,000 high-risk, stable patients 65 years or older who underwent nonemergent revascularization for 2- and 3-vessel coronary disease found that adjusted 4-year all-cause mortality was about 20% lower after coronarycoronary- artery bypass grafting (CABG) surgery than after percutaneous

coronary intervention (PCI). One-year mortality was similar for the 2 procedures.

The ASCERT (ACCF and STS Database Collaboration on the Comparative Effectiveness of Revascularization Strategies) trial combined data from the American College of Cardiology Foundation (ACCF) CathPCI registry, the Society of Thoracic Surgeons (STS) CABG database, and Medicare claims. William S. Weintraub, MD, of the Christiana Care Health System in Newark, Delaware, and colleagues said the study showed that the long-term advantage of CABG was independent of age,

sex, diabetes, renal function, and lung disease, and was evident even among patients whose propensity scores were most consistent with selection for PCI. The researchers had expected to find subsets of patients who would benefit from surgery and others who would benefit from PCI. “To our surprise, all of the subsets showed a survival advantage for surgery,” noted study co-author Fred H. Edwards, MD, of the University of Florida, Jacksonville.

The researchers acknowledge that the study is limited by their inability to adjust for all potential confounders. Unmeasured confounders such as patient preference, angiogram, bleeding risk, and compliance with therapy were cited during a panel discussion as variables that are not easily measured but which go into clinical decision making about which treatment is best for a particular patient. Such variables and more nuanced factors were not collected in this database. Dr Edwards noted that a major takeaway message of the study is that cardiologists and surgeons need to be talking to each other more and taking a true team approach to treatment.

“Hopefully, ASCERT will prompt more than just lip service,” he said.

This study is supported by a grant from the National Heart, Lung, and Blood Institute. Weintraub WS, Grau-Sepulveda MN, Weiss JM, et al. Comparative effectiveness of revascularization strategies [published online ahead of print March 27, 2012]. N Engl J Med. doi:10.1056/NEJMoa1110717.