Stroke risk and vitamin D, everyone was wrong about nesiritide, Rx omega-3 is useless, anacetrapib puts new focus on HDL -- what else did we learn?
The American Heart Association Scientific Sessions 2010, held November 13-17 in Chicago, IL, featured a variety of exciting announcements from key studies focusing on the diagnosis, treatment and prevention of cardiovascular disease and stroke. Below, we summarize the results from 10 of the most interesting studies.
Analysis of data from the Third National Health and Nutrition Examination Survey of Americans (NHANES-III) revealed that although vitamin D deficiency nearly doubled the risk of fatal stroke among Caucasians, there was no corresponding relationship between fatal strokes and vitamin D deficiency among African Americans. Lead researcher Erin Michos, MD, MHS, assistant professor of medicine at Johns Hopkins University School of Medicine, said that the results were surprising because not only were African Americans in the study much more likely to be vitamin D deficient compared to their Caucasian counterparts (32% vs. 7%), African Americans in the study also had a 60% higher risk of dying from stroke compared to Caucasians. “We thought maybe the lower vitamin D levels might actually explain why blacks have higher risks for stroke… But we did not find the same relationship between vitamin D and stroke in blacks,” he said.
Results from the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial presented at the American Heart Association Scientific Sessions 2010 revealed that the although use of nesiritide in patients with decompensated heart failure did not increase the risk of death or renal failure, it was also not much better than placebo in improving breathing function. Robert M. Califf, MD, study chair and vice chancellor for clinical research at Duke University School of Medicine, said that ““Now that we finally have a proper clinical trial we know that both perceptions [about the risks and benefits of nesiritide] were incorrect; nesiritide is safe but has only a modest effect on dyspnea. This is a major signal that we must do a better job defining the biological effects of drugs early in development and conduct adequately powered outcomes trials much earlier to give doctors and patients the necessary information to enable appropriate use of the treatment in practice.”
Results from the Eplerenone in Mild Patients Hospitalization And Survival Study in Heart Failure (EMPHASIS-HF) trial confirmed that patients with New York Heart Association class II heart failure and an ejection fraction of no more than 35% who received treatment with the aldosterone antagonist eplerenone had a 37% reduced combined risk of death and hospitalization compared to patients who received placebo. Lead author Faiez Zannad, MD, PhD, professor of therapeutics and director of the Clinical Investigation Center at the Nancy University Hospital Center in Nancy, France, said he thinks that “This treatment is certainly going to change the guidelines for mild heart failure. Now patients with all kinds of severity of systolic heart failure, whether it is post-myocardial infarction, with mild or severe symptoms, are potentially eligible for some kind of aldosterone blockade, and, certainly, for eplerenone.”
Analysis of data from the Efficacy and Safety of Prescription Omega-3 Acid Ethyl Esters (P-OM3) for the Prevention of Recurrent Symptomatic Atrial Fibrillation trial found that patients with paroxysmal atrial fibrillation (AF) treated with prescription omega-3 experienced no significant reduction in time to first recurrence of symptoms compared to patients who received placebo. Researchers also reported no significant difference between treated persistent AF and the placebo group. Lead author Peter R. Kowey, MD, chief of cardiology at Main Line Health Hospital System near Philadelphia, PA, said that “The trial’s major implication is that using prescription omega-3 in the vast majority of paroxysmal atrial fibrillation patients who do not have significant heart disease is fruitless… In the absence of any data that it works, it is probably better not to take prescription omega-3.” However, Kowey and his fellow researchers were careful to point out that these findings should not be applied to omega-3 ingested from fish; “This was not a dietary study; this was a product manufactured from fish oil,” Kowey said.
Rivaroxaban is just as effective as warfarin in preventing stroke and embolism in patients with atrial fibrillation, without increasing their risk of bleeding. Robert M. Califf, MD, vice chancellor for clinical research at Duke University School of Medicine and co-principal investigator of the Stroke Prevention Using the Oral Direct Factor Xa Inhibitor Rivaroxaban Compared With Warfarin in Patients with Nonvalvular Atrial Fibrillation (ROCKET-AF) trial said that the availability of an alternative to warfarin that doesn’t raise bleeding risk means that “we have a drug you can take once a day, without monitoring, which is at least as good as warfarin and causes no additional risk.”
Results from the Gauging Responsiveness With A VerifyNow Assay — Impact on Thrombosis and Safety (GRAVITAS) trial showed that giving patients with high residual platelet reactivity implanted with drug-coated stents (who face a higher risk of major post-stent cardiovascular events) double the dose of the blood-thinner clopidogrel does not reduce the incidence of death, heart attack, or blood clots. Lead investigator Matthew Price, MD, director of the Cardiac Catheterization Laboratory at the Scripps Clinic and assistant professor at the Scripps Translational Science Institute in La Jolla, CA, said “The high dose of clopidogrel doesn’t appear to improve outcomes, so alternative treatment strategies should be tested.”
In one of the most anticipated presentations of this year’s conference, researchers from the Determining the EFficacy and Tolerability of CETP INhibition with AnacEtrapib (DEFINE) reported that the experimental cholesterol drug anacetrapib reduced LDL by 40% and more than doubled HDL without raising blood pressure in patients who were already taking statins or other lipid-lowering agents. Christopher Cannon, MD, senior investigator of the TIMI Study Group in the cardiovascular division of Brigham and Women’s Hospital, said that “Anacetrapib has a knock-your-socks-off effect on HDL and a jaw-dropping effect on LDL.” Cannon also said that “These changes are striking because virtually all the patients in the study were already taking cholesterol-lowering drugs and achieved previously unattainable levels of good and bad cholesterol… If the cardiovascular effects are borne out by future research, it would be a very promising approach to reducing cardiovascular events in patients with or prone to atherosclerosis.”
Quick Hits from AHA 2010
Although determining whether a patient is truly statin-intolerant can be difficult, clinicians who treat these patients do have several alternative medications from which to choose. However, researchers are divided on the merits of some of these options.
Studies show that nearly one in four patients does not fill their initial prescription, and even if they do, adherence often decreases over time. Part of the problem is that non-adherence is under-recognized among providers and therefore undertreated. Effective interventions incorporate tailored instruction, frequent communication and counseling, and input from clinicians along the continuum of care, especially pharmacists. One particularly successful strategy is the ACE-ME model, which emphasizes the collaborative approach to adherence.
Results from the Multi-Ethnic Study of Atherosclerosis (MESA) show that adherence to the AHA’s “Life’s Simple 7” approaches to cardiovascular health (which include not smoking, keeping BMI below 25, keeping cholesterol below 200 mg/dL, and keeping blood pressure below 120/80 mm Hg) is associated with lower incidence of cardiovascular disease.