Lisinopril tied to 19% drop in conduction system disease

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Exciting results merit further study

To our knowledge, this is the first report that incident conduction system disease may be prevented by drug therapy, in this case lisinopril. This important observation is consistent with established knowledge that angiotensin-converting enzyme inhibition has salutary effects on inflammation, hypertrophy, and fibrosis. We look forward to future studies to confirm that ECG conduction disease can indeed be prevented or progression slowed by relatively simple interventions, to define those individuals most likely to benefit, and to assess whether such preventive strategies can indeed ward off the need for invasive procedures such as pacemakers in selected patient subsets. This is indeed an exciting prospect!

Dr. Sanjiv M. Narayan, Dr. Tina Baykaner, and Dr. David J. Maron are at Falk Cardiovascular Research Center, Stanford University, Palo Alto, California. Dr. Narayan reported receiving research support from the National Institutes of Health; being coinventor of intellectual property owned by the University of California and licensed to Topera, in which he held equity; and receiving consulting fees from the American College of Cardiology and and speaking fees from St. Jude Medical and Medtronic. The other authors had no disclosures. These comments are from their editorial (JAMA Intern Med. 2016 Jun 27. doi: 10.1001 /jamainternmed.2016.2502).




Compared with chlorthalidone, the angiotensin-converting enzyme inhibitor lisinopril was associated with a 19% drop in new-onset conduction system disease among high-risk patients with hypertension, based on a secondary analysis of the randomized, double-blind Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).


Amlodipine besylate and pravastatin did not affect rates of conduction defects, added Dr. Thomas A. Dewland of Oregon Health and Science University, Portland, and his associates, who reported the findings online June 27 in JAMA Internal Medicine.

ALLHAT was a randomized, double-blind trial comparing chlorthalidone, amlodipine, lisinopril, or doxazosin mesylate in patients with hypertension and at least one other cardiac risk factor. Patients with elevated fasting low-density lipoprotein levels also were randomized to pravastatin sodium or usual care. Most (56%) patients were men, and the average age was about 67 years (standard deviation, 7.3 years). Twelve-lead electrocardiograms were obtained every 2 years, enabling the current analysis, the researchers said. In all, 21,004 patients without a baseline pacemaker or conduction system disease were followed for an average of 5 years (JAMA Intern Med. 2016 Jun 27. doi: 10.1001/jamainternmed.2016.250).

A total of 1,114 patients developed new-onset conduction system disease (3 events per 1,000 person-years), including 389 patients with left bundle branch block (4.5 events per 1,000 person-years), 570 patients with right bundle branch block (6.6 events per 1,000 person-years), and 155 patients with intraventricular conduction delay. The risk of conduction system disease was 19% lower with lisinopril than chlorthalidone (hazard ratio, 0.81; 95% confidence interval, 0.69-0.95; P = .01). Neither amlodipine nor pravastatin significantly affected the chances of conduction system disease, but patients who were older, white, or had diabetes or left ventricular hypertrophy were at significantly greater risk than the overall cohort.

“The antifibrotic effects of angiotensin-converting enzyme inhibitors may prevent or slow the development of conduction system disease, and future research is warranted to understand whether this treatment affects other conduction-related clinical outcomes,” including the need for pacemaker implantation, the researchers concluded.

The study was supported by the American Heart Association, the Joseph Drown Foundation, the National Heart, Lung, and Blood Institute of the National Institutes of Health, and by Pfizer. The investigators had no disclosures.

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