By Brandon Kopceuch
A post hoc analysis of the ATHENA (A Placebo-controlled, Double-blind, Parallel Arm Trial to Assess the Efficacy of Dronedarone 400 mg BID for the Prevention of Cardiovascular Hospitalization or Death from Any Cause in Patients with Atrial Fibrillation/Atrial Flutter) trial presented at the 2008 American Heart Association Scientific Sessions found that dronedarone (Multaq) significantly reduced the occurrence of hospitalization and the length of hospital stays in patients with atrial fibrillation (AF). Compared with placebo, dronedarone reduced the total amount of hospital days by 28% (9995 vs 13,986 days) and decreased the amount of time spent in the hospital for heart-related conditions by 35% (5875 vs 9073 days). It also showed that dronedarone reduced the occurrence of AF-related hospitalization by 37%, while reducing initial non-AF cardiovascular hospitalization by 14%. Statistical analyses revealed that patients with normal heart rhythm at the start of the ATHENA trial had their time to a first recurrence of AF reduced by 25% when compared with placebo.
Multaq, which is to be marketed by sanofi-aventis, is currently being reviewed by health regulators in the United States and Europe. If approved, researchers say that it could be a safer option than amiodarone, which is commonly used for irregular heartbeats but associated with lung and thyroid gland toxicities. “Why would I consider prescribing amiodarone if I can give a drug like [dronedarone] that is effective, but does not have amiodarone’s toxicities?” said Richard Page, MD, a lead investigator of the study and head of the division of cardiology at the University of Washington School of Medicine. Dr Page noted, however, that a head-to-head trial directly comparing amiodarone with dronedarone has not yet been undertaken.
According to Christian Torp-Pederson, MD, from the Gentofte University Hospital in Copenhagen, and a member of the study’s steering committee, the incidence of AF-related hospital stays is increasing rapidly “and therapeutic solutions to reduce this burden are needed…These new data showed that, for the first time, an antiarrhythmic drug significantly and consistently reduced hospitalization incidence and duration, which led to a substantial reduction in total hospitalization burden in this patient population.”
When asked what he thought about this study, Suneet Mittal, MD, from St. Luke’s-Roosevelt Hospital Center in New York, and a member of the Cardiology Review editorial board, commented that “Dronedarone represents a potentially important addition to the armamentarium of anti-arrhythmic medications. Impressively, when used in elderly patients at moderate to high risk of developing AF, dronedarone reduced the likelihood of developing AF as compared with placebo.” Dr Mittal also noted that a major advantage of dronedarone is that it reduces cardiovascular hospitalizations and death. “However, more data are needed with respect to its safety in patients with underlying left ventricular dysfunction and congestive heart failure,” he cautioned.
The ATHENA trial is the largest, antiarrhythmic, morbidity-mortality study ever conducted in AF. The trial was done at more than 550 sites in 37 countries and consisted of 4628 patients who were either 75 years or older (with or without cardiovascular risk) or younger than 75 years and with at least 1 cardiovascular risk factor. It did not include individuals with decompensated heart failure. The patients were randomized to receive either dronedarone 400 mg twice daily or placebo, and they were then followed-up for a maximum of 30 months.
Home INR monitoring is alternative to monthly clinic visits
By Wayne Kuznar
Home monitoring of international normalized ratio (INR) values is a feasible alternative to monthly clinic visits in patients on chronic warfarin therapy, said David Matchar, MD, director of the Duke Center for Clinical Health Policy Research, Durham, NC. Patients who may find home INR testing attractive are those who are disabled or live far from clinics, making access to routine care difficult. “In typical clinical practice, warfarin is underutilized, with fewer than half of patients in some settings receiving anticoagulation,” said Dr Matchar. “The quality of management can be poor, with patients in the therapeutic range less than half the time.”
In the study conducted by Dr Matchar, which was funded by the US Department of Veterans Affairs, weekly patient self-testing was compared with monthly clinic testing of INR in 2922 patients who were on chronic warfarin therapy with indications for mechanical heart valves or atrial fibrillation (AF). Patients randomized to home testing were trained in its use. “The training took about a half hour. The patients were given the devices to take home, used them for 2 to 4 weeks, and then were retested [for competency],” Dr Matchar said.
With an average of 3 years of follow-up, there was no significant difference between the 2 groups on the primary composite end point of stroke, major bleeds, or death; this end point occurred in 7.9% of patients assigned to home INR monitoring and 8.9% of the clinically tested patients.
Home INR testing did show significant superiority to high-quality clinic monitoring on the secondary end point, which was time that INR was in the therapeutic range. The cumulative amount of time in the therapeutic range exceeded 60% in both groups; the time in the target range was improved by about 7% in the home INR monitoring group, said Dr Matchar. By the end of the study, the time in the target range was nearly 70% in the home INR monitoring group and about 60% in the monthly monitoring group. Furthermore, satisfaction scales revealed higher satisfaction with home INR monitoring.
Anticoagulation clinics “require patients to come to a centralized location, which limits the potential to perform high-frequency testing, and, in some cases, may limit access to anticoagulation treatment because of difficulties with travel for testing and management,” he said. Although this study showed no difference in clinical outcomes between the 2 strategies, a previous study of more than 13,000 patients with AF demonstrated that as time in the therapeutic INR range increased, the number of thromboembolic events prevented also increased and the number of intracranial hemorrhages decreased, noted Alan Go, MD, from Kaiser Permanente of Northern California.
Dr Go said that “regardless of the approach, high-quality management of anticoagulation leads to low rates of ischemic stroke and intracranial hemorrhage in patients with AF or mechanical heart valves.” He noted, however, that the resource utilization and cost implications of home INR monitoring should be assessed.
Microalbuminuria linked with coronary calcium
By Wayne Kuznar
In asymptomatic persons, microalbuminuria predicts the presence of coronary artery calcium and its progression, said Andrew P. DeFilippis, MD, Johns Hopkins Ciccarone Preventive Cardiology Center, Baltimore, MD. This finding comes from a subset of the MESA (Multi-Ethnic Study of Atherosclerosis) study, a project initiated in 2000 to investigate the prevalence, correlates, and progression of subclinical cardiovascular disease in a population-based sample of 6500 middle-aged and older adults. MESA included white, black, Chinese American, and Hispanic ethnicities.
Data on urinary albumin:creatinine ratio (UACR) were available for 5666 of the subjects. The association between microalbuminuria, defined as UACR of 30 to 300 mg/g, and incident coronary artery calcium and progression of coronary artery calcium was assessed. Of the subjects with microalbuminuria, 62% had coronary artery calcium at baseline compared with 48% without microalbuminuria (P <.001). At a median follow-up of 2.4 years, microalbuminuria increased the odds of developing coronary artery calcium over the course of the study by 76% (P = .005). As a continuous variable, the presence of microalbuminuria remained significant as a predictor of the development of coronary artery calcium (P = .016). Among those with coronary artery calcium at baseline, the risk of progression of the disease was 9-fold higher among those with microalbuminuria (P = .009). When microalbuminuria was examined as a continuous variable, those with microalbuminuria were 3 times as likely to have progression of their coronary calcium (P = .009).
Americans’ LDL cholesterol is falling but triglycerides are up; obesity is the culprit
By Wayne Kuznar
A new 30-year analysis of the National Health and Nutrition Examination Surveys (NHANES) shows a favorable downward trend in levels of low-density lipoprotein (LDL) cholesterol in the US population, but an increase in nonoptimal levels of triglycerides, reports Jerome D. Cohen, MD, of the National Lipid Association, and professor emeritus, St. Louis University. The increase in triglyceride levels strongly correlates with obesity over the 3 surveys, he noted.
Lipid values in adults aged 20 to 74 years were compared between NHANES conducted between 1976 and 1980 (NHANES II), 1988 and 1994 (NHANES III), and NHANES 1999-2006 (NHANES). The presence of abnormal LDL cholesterol as a single abnormality fell from 43.48% to 40.13% from NHANES II to the most recent NHANES. At the same time, the presence of abnormal triglycerides as a single abnormality increased from 2.42% to 5.53%, and the prevalence of abnormal triglycerides plus abnormal high-density lipoprotein (HDL) cholesterol doubled from 2.1% to 4.0%.
“It’s a good news, bad news, situation,” said Dr Cohen. “We are achieving the Healthy People Initiative 2010 goal of a total cholesterol less than 200 mg/dL. The average cholesterol in the latest survey was about 200 mg/dL. What’s driving this reduction is a lowering of LDL. As more people are taking statins, the average cholesterol has come down. The increase in triglycerides is the bad news, and this increase was not surprising given the increase in body mass index (BMI) and the growing prevalence of obesity,” he noted. In the most recent survey, about one third of subjects qualified as obese based on their BMI (>30 kg/m2), compared with only 15% in the earliest survey.
The study also revealed a strong increase in elevated triglyceride levels among people older than 60 years, with the likelihood of having unhealthy triglycerides increasing nearly 5-fold from 1.8% in 1976-1980 to 8.7% in 1999-2006. Researchers involved with the study concluded that patients’ triglyceride levels require more vigilant monitoring in an effort to improve preventive care.
Lifestyle changes (ie, weight loss through healthier eating and exercise) should be encouraged in patients with elevated triglycerides, including those with metabolic syndrome and type 2 diabetes, who often exhibit high triglycerides in addition to low levels of HDL cholesterol, said Dr Cohen.
Patients and physicians need to understand the importance and role of all 3 lipids in cardiovascular risk. Motivating patients to make lifestyle changes may require education and the use of dieticians in practice; patients often aren’t motivated to make such changes until they experience chest pain and require angiography, noted Dr Cohen. Pharmacologic options, such as fish oil, niacin, and fibrates (fenofibrate and clofibrate) are useful in reducing triglyceride levels as an option beyond diet and exercise, he said. There may be some resistance to niacin because of flushing, although a long-acting formulation reduces this problem.
Fibrates can reduce triglyceride levels by approximately 50%. Some fibrates interact with statins to increase the risk of myopathy. In using a fibrate and statin together, “I’ll start with a nonmaximal dose of a statin and see how the patient tolerates it before increasing the dose,” said Dr Cohen.
Patients misperceive reasons for elective PCI
By Wayne Kuznar
Patients misperceive the benefits of elective percutaneous coronary intervention (PCI), said John H. Lee, MD, fellow in preventive cardiology at the Mid America Heart Institute, Kansas City, MO.
About 1 million PCIs are performed annually in the United States, with the majority being elective. When performed for acute coronary syndromes, PCI has been shown to reduce the incidence of death, myocardial infarction (MI), and hospitalization. “In the elective setting, the benefits are less clear,” said Dr Lee, pointing to the results of the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) study, in which medical therapy was equivalent to PCI on the end point of ischemic events in patients with stable coronary artery disease. The only definitive benefit to PCI in the elective setting is relief of angina and improvement in quality of life, he said.
To assess patients’ perceptions of the benefits of elective PCI, 498 consecutive patients who received an elective PCI between January 2006 and October 2007 were mailed 1-page questionnaires, of which 350 responded. The questionnaires sought to elicit the patients’ beliefs about the benefits from their elective PCI in the preceding year. The mean age of the respondents was 67.8 years and 76% were men.
The respondents’ beliefs were as follows:
71% said that they thought the PCI would prevent a future MI
66% thought that it extended their life
42% responded that it saved their life
42% indicated that it was done to improve an abnormality on their stress test
31% responded that PCI was performed for angina relief
33% thought that their PCI was emergent
According to the patients, 18% were offered medical therapy, 13% were offered coronary artery bypass graft surgery, and 68% were offered no alternative. The results were not significantly different when comparing responses before and after the release of the COURAGE study in 2007. Better education of patients is needed prior to elective PCI to facilitate informed consent, said Dr Lee.
ATHENA trial post hoc analysis shows dronedarone significantly reduced hospitalization incidence and duration