Conduction System Disease in the ALLHAT Trial

Study Questions:

When it comes to individuals ≥55 years old with hypertension and ≥1 other cardiac risk factor, does treatment with amlodipine, lisinopril, or chlorthalidone impact the risk of incident conduction system abnormalities?

Methods:

This was a secondary analysis of the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) study. Individuals ≥55 years old with hypertension and ≥1 other cardiac risk factor were randomized to receive amlodipine, lisinopril, or chlorthalidone. Individuals with elevated low-density lipoprotein levels were also randomized to pravastatin versus usual care. An electrocardiogram (ECG) was obtained at enrollment and every 2 years. The development of incident conduction system abnormalities was analyzed.

Results:

A total of 21,004 participants (56.0% men; mean age, 66.5 years) were followed for 5 years. Among the 1,114 patients who developed any conduction defect, 389 developed left bundle branch block, 570 developed right bundle branch block, and 155 developed intraventricular conduction delay. Compared with chlorthalidone, treatment with lisinopril was associated with a significant 19% reduction in conduction abnormalities. Treatment with amlodipine, however, was not associated with a significant difference in conduction outcome events. Similarly, pravastatin treatment was not associated with reduction in adjusted risk for incident conduction system disease compared with usual hyperlipidemia treatment. Increasing age, male sex, and left ventricular hypertrophy were among predictors of incident conduction system disease, whereas black individuals had significantly less conduction system disease compared with white individuals.

Conclusions:

Treatment with lisinopril reduces incident conduction system disease. It remains unknown whether pharmacologic treatment affects conduction abnormality outcomes, including pacemaker implantation.

Perspective:

This is the first study to suggest that a pharmacologic treatment may reduce the incidence of conduction system disease. The significant reduction in conduction system disease with lisinopril cannot be fully explained by its antihypertensive effects. Blood pressures were actually higher in the lisinopril treatment group compared with the chlorthalidone or amlodipine group. Perhaps the angiotensin-converting enzyme inhibitor’s anti-inflammatory and anti-fibrotic properties, or its effect on left ventricular hypertrophy, play a key role in reducing the risk of conduction system disease.

Clinical Topics: Arrhythmias and Clinical EP, Clinical Topic Collection: Dyslipidemia, Prevention, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Lipid Metabolism, Statins, Hypertension

Keywords: Amlodipine, Angiotensin-Converting Enzyme Inhibitors, Antihypertensive Agents, Arrhythmias, Cardiac, Anti-Arrhythmia Agents, Bundle-Branch Block, Chlorthalidone, Electrocardiography, Heart Conduction System, Hyperlipidemias, Hypertension, Hypertrophy, Left Ventricular, Lipoproteins, LDL, Lisinopril, Myocardial Infarction, Pacemaker, Artificial, Pravastatin, Primary Prevention, Risk Factors


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