Keeping the Heart’s Electrical System Running

By Scott Maier

illustratin of a heart EKGA drug commonly used to treat high blood pressure has been shown to significantly reduce the risk of blocked electrical impulses to the heart and could be an effective treatment for certain types of heart disease known as conduction disease, in which the progression of electrical impulses through the heart is impeded, according to researchers at UCSF and Oregon Health & Science University (OHSU).

Their study, which compared the effectiveness of the drug lisinopril against two other blood pressure medications, as well as a cholesterol drug and a control, appeared online June 27 in JAMA Internal Medicine.

“Despite our success in preventing coronary heart disease, we have yet to rigorously identify potential strategies to prevent conduction disease of the heart, a common cause of pacemaker implantation and likely an important contributor to heart failure,” said senior author Gregory Marcus, MD, MAS, a UCSF Health cardiologist and director of clinical research in the UCSF Division of Cardiology. “Because these patients were randomly assigned to lisinopril therapy, these findings favor a causal relationship between the drug and a reduced risk of conduction disease.”

In the JAMA Internal Medicine study, Marcus and his colleagues utilized electrocardiograms at enrollment and every two years of follow up for eight years from the National Institutes of Health-funded ALLHAT (Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial).

Of 42,418 overall ALLHAT study participants age 55 or older with hypertension and at least one other cardiac risk factor, 21,004 individuals were enrolled and randomly assigned to receive one of three drugs commonly prescribed to treat high blood pressure and other symptoms: amlodipine, lisinopril or chlorthalidone. In addition, 10,355 study participants with elevated cholesterol levels were randomized to either the high cholesterol drug pravastatin or standard care.

The researchers hypothesized that the drug lisinopril, an angiotensin converting enzyme (ACE) inhibitor purported to have anti-fibrotic activities, would be associated with a lower risk of conduction disease. Indeed, compared to chlorthalidone, those on lisinopril had a 19 percent reduction in conduction abnormalities.

The study found that amlodipine was not associated with a significant reduction in conduction disease, and that pravastatin was no better than standard care.

Over an average five-year period, 1,114 of the 21,004 participants (5.3 percent) still developed conduction disease, including 389 with a delay or blockage of electrical impulses to the left side of the heart, 570 to the right side of the heart and 155 in the ventricles themselves.

The authors said further studies are needed to determine whether the pharmacologic treatments have an impact on patient outcomes due to conduction abnormalities, including the need for pacemaker implants.

“Our analysis also allowed us to identify certain patient characteristics, including increased age, male gender, white race and diabetes, that were associated with heightened risk of conduction system disease,” said lead author Thomas Dewland, MD, OHSU assistant professor and former UCSF resident and cardiology electrophysiology fellow. “These results may help guide future studies aimed at preventing conduction abnormalities in high-risk patients.”

Other contributors to the JAMA Internal Medicine study were Elsayed Soliman, MD, MSc, MS, Wake Forest School of Medicine; Barry Davis, MD, Jose-Miguel Yamal, PhD, and Linda Piller, MD, MPH, The University of Texas School of Public Health at Houston; Jared Magnani, MD, MSc, Boston University School of Medicine; L. Julian Haywood, MD, University of Southern California; Alvaro Alonso, MD, PhD, University of Minnesota School of Public Health; and Christine Albert, MD, MPH, Brigham and Women’s Hospital and Harvard Medical School.

Financial support was provided by grant number 12POST11810036 from the American Heart Association and the Joseph Drown Foundation and contracts NO1-HC-35130 and HHSN268201100036C with the National Heart, Lung, and Blood Institute. The ALLHAT investigators acknowledge contributions of study medications by Pfizer Inc. (amlodipine), AstraZeneca (lisinopril) and Bristol-Myers Squibb (pravastatin), with financial support by Pfizer Inc.

UC San Francisco (UCSF) is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy; a graduate division with nationally renowned programs in basic, biomedical, translational and population sciences; and a preeminent biomedical research enterprise. It also includes UCSF Health, which comprises two top-ranked hospitals, UCSF Medical Center and UCSF Benioff Children’s Hospital San Francisco, and other partner and affiliated hospitals and healthcare providers throughout the Bay Area.