Effect of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) on conduction system disease

Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Collaborative Research Group

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Importance: Cardiac conduction abnormalities are associated with an increased risk for morbidity and mortality, and understanding factors that accelerate or delay conduction system disease could help to identify preventive and therapeutic strategies. Antifibrotic and anti-inflammatory properties of angiotensin-converting enzyme inhibitors and treatment for hyperlipidemia may reduce the risk for incident conduction system disease. Objective: To identify the effect of pharmacologic therapy randomization and clinical risk factors on the incidence of conduction system disease. Design, Setting, and Participants: This secondary analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) investigation acquired data from 623 North American centers. A total of 21 004 ambulatory individuals 55 years or older with hypertension and at least 1 other cardiac risk factor were included in the analysis. Interventions: Participants were randomly assigned to receive amlodipine besylate, lisinopril, or chlorthalidone. Individuals with elevated fasting low-density lipoprotein cholesterol levels were also randomized to pravastatin sodium vs usual care. Main Outcomes and Measures: An electrocardiogram (ECG) was obtained at study enrollment and every 2 years of follow-up. The development of incident first-degree atrioventricular block, left anterior fascicular block, incomplete left bundle branch block (LBBB), LBBB, incomplete right bundle branch block (RBBB), RBBB, or intraventricular conduction delay was assessed by serial ECGs. Results: The 21 004 participants (11 758 men [56.0%]; 9246 women [44.0%]; mean [SD] age, 66.5 [7.3] years) underwent a mean (SD) follow-up of 5.0 (1.2) years. Among the 1114 participants who developed any conduction defect, 389 developed LBBB, 570 developed RBBB, and 155 developed intraventricular conduction delay. Compared with chlorthalidone, randomization to lisinopril was associated with a significant 19% reduction in conduction abnormalities (hazard ratio [HR], 0.81; 95%CI, 0.69-0.95; P = .01). Treatment with amlodipine, however, was not associated with a significant difference in conduction outcome events (HR, 0.94; 95%CI, 0.81-1.09; P = .42). Similarly, pravastatin treatment was not associated with a reduced adjusted risk for incident disease compared with usual hyperlipidemia treatment (HR, 1.13; 95%CI, 0.95-1.35; P = .18). Increased age (HR, 1.47; 95% CI, 1.34-1.63; P <.001), male sex (HR, 0.59; 95%CI, 0.50-0.73; P <.001), white race (HR, 0.59; 95%CI, 0.50-0.70; P <.001), diabetes (HR, 1.23; 95%CI, 1.07-1.42; P = .003), and left ventricular hypertrophy (HR, 3.20; 95%CI, 2.61-3.94; P <.001) were also independently associated with increased risk for conduction system disease. Conclusions and Relevance: Incident conduction system disease is significantly reduced by lisinopril therapy and is independently associated with multiple clinical factors. Further studies are warranted to determine whether pharmacologic treatment affects conduction abnormality outcomes, including pacemaker implantation.

Original languageEnglish (US)
Pages (from-to)1085-1092
Number of pages8
JournalJAMA Internal Medicine
Volume176
Issue number8
DOIs
StatePublished - Aug 1 2016

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Antihypertensive Agents
Bundle-Branch Block
Myocardial Infarction
Lipids
Lisinopril
Chlorthalidone
Pravastatin
Amlodipine
Therapeutics
Random Allocation
Hyperlipidemias
Electrocardiography
Atrioventricular Block
Sex Ratio
Left Ventricular Hypertrophy
Angiotensin-Converting Enzyme Inhibitors
LDL Cholesterol
Fasting
Anti-Inflammatory Agents
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Collaborative Research Group (2016). Effect of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) on conduction system disease. JAMA Internal Medicine, 176(8), 1085-1092. https://doi.org/10.1001/jamainternmed.2016.2502

Effect of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) on conduction system disease. / Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Collaborative Research Group.

In: JAMA Internal Medicine, Vol. 176, No. 8, 01.08.2016, p. 1085-1092.

Research output: Contribution to journalArticle

Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Collaborative Research Group 2016, 'Effect of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) on conduction system disease', JAMA Internal Medicine, vol. 176, no. 8, pp. 1085-1092. https://doi.org/10.1001/jamainternmed.2016.2502
Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Collaborative Research Group. Effect of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) on conduction system disease. JAMA Internal Medicine. 2016 Aug 1;176(8):1085-1092. https://doi.org/10.1001/jamainternmed.2016.2502
Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Collaborative Research Group. / Effect of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) on conduction system disease. In: JAMA Internal Medicine. 2016 ; Vol. 176, No. 8. pp. 1085-1092.
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abstract = "Importance: Cardiac conduction abnormalities are associated with an increased risk for morbidity and mortality, and understanding factors that accelerate or delay conduction system disease could help to identify preventive and therapeutic strategies. Antifibrotic and anti-inflammatory properties of angiotensin-converting enzyme inhibitors and treatment for hyperlipidemia may reduce the risk for incident conduction system disease. Objective: To identify the effect of pharmacologic therapy randomization and clinical risk factors on the incidence of conduction system disease. Design, Setting, and Participants: This secondary analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) investigation acquired data from 623 North American centers. A total of 21 004 ambulatory individuals 55 years or older with hypertension and at least 1 other cardiac risk factor were included in the analysis. Interventions: Participants were randomly assigned to receive amlodipine besylate, lisinopril, or chlorthalidone. Individuals with elevated fasting low-density lipoprotein cholesterol levels were also randomized to pravastatin sodium vs usual care. Main Outcomes and Measures: An electrocardiogram (ECG) was obtained at study enrollment and every 2 years of follow-up. The development of incident first-degree atrioventricular block, left anterior fascicular block, incomplete left bundle branch block (LBBB), LBBB, incomplete right bundle branch block (RBBB), RBBB, or intraventricular conduction delay was assessed by serial ECGs. Results: The 21 004 participants (11 758 men [56.0{\%}]; 9246 women [44.0{\%}]; mean [SD] age, 66.5 [7.3] years) underwent a mean (SD) follow-up of 5.0 (1.2) years. Among the 1114 participants who developed any conduction defect, 389 developed LBBB, 570 developed RBBB, and 155 developed intraventricular conduction delay. Compared with chlorthalidone, randomization to lisinopril was associated with a significant 19{\%} reduction in conduction abnormalities (hazard ratio [HR], 0.81; 95{\%}CI, 0.69-0.95; P = .01). Treatment with amlodipine, however, was not associated with a significant difference in conduction outcome events (HR, 0.94; 95{\%}CI, 0.81-1.09; P = .42). Similarly, pravastatin treatment was not associated with a reduced adjusted risk for incident disease compared with usual hyperlipidemia treatment (HR, 1.13; 95{\%}CI, 0.95-1.35; P = .18). Increased age (HR, 1.47; 95{\%} CI, 1.34-1.63; P <.001), male sex (HR, 0.59; 95{\%}CI, 0.50-0.73; P <.001), white race (HR, 0.59; 95{\%}CI, 0.50-0.70; P <.001), diabetes (HR, 1.23; 95{\%}CI, 1.07-1.42; P = .003), and left ventricular hypertrophy (HR, 3.20; 95{\%}CI, 2.61-3.94; P <.001) were also independently associated with increased risk for conduction system disease. Conclusions and Relevance: Incident conduction system disease is significantly reduced by lisinopril therapy and is independently associated with multiple clinical factors. Further studies are warranted to determine whether pharmacologic treatment affects conduction abnormality outcomes, including pacemaker implantation.",
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T1 - Effect of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) on conduction system disease

AU - Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Collaborative Research Group

AU - Dewland, Thomas

AU - Soliman, Elsayed Z.

AU - Davis, Barry R.

AU - Magnani, Jared W.

AU - Yamal, Jose Miguel

AU - Piller, Linda B.

AU - Haywood, L. Julian

AU - Alonso, Alvaro

AU - Albert, Christine M.

AU - Marcus, Gregory M.

PY - 2016/8/1

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N2 - Importance: Cardiac conduction abnormalities are associated with an increased risk for morbidity and mortality, and understanding factors that accelerate or delay conduction system disease could help to identify preventive and therapeutic strategies. Antifibrotic and anti-inflammatory properties of angiotensin-converting enzyme inhibitors and treatment for hyperlipidemia may reduce the risk for incident conduction system disease. Objective: To identify the effect of pharmacologic therapy randomization and clinical risk factors on the incidence of conduction system disease. Design, Setting, and Participants: This secondary analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) investigation acquired data from 623 North American centers. A total of 21 004 ambulatory individuals 55 years or older with hypertension and at least 1 other cardiac risk factor were included in the analysis. Interventions: Participants were randomly assigned to receive amlodipine besylate, lisinopril, or chlorthalidone. Individuals with elevated fasting low-density lipoprotein cholesterol levels were also randomized to pravastatin sodium vs usual care. Main Outcomes and Measures: An electrocardiogram (ECG) was obtained at study enrollment and every 2 years of follow-up. The development of incident first-degree atrioventricular block, left anterior fascicular block, incomplete left bundle branch block (LBBB), LBBB, incomplete right bundle branch block (RBBB), RBBB, or intraventricular conduction delay was assessed by serial ECGs. Results: The 21 004 participants (11 758 men [56.0%]; 9246 women [44.0%]; mean [SD] age, 66.5 [7.3] years) underwent a mean (SD) follow-up of 5.0 (1.2) years. Among the 1114 participants who developed any conduction defect, 389 developed LBBB, 570 developed RBBB, and 155 developed intraventricular conduction delay. Compared with chlorthalidone, randomization to lisinopril was associated with a significant 19% reduction in conduction abnormalities (hazard ratio [HR], 0.81; 95%CI, 0.69-0.95; P = .01). Treatment with amlodipine, however, was not associated with a significant difference in conduction outcome events (HR, 0.94; 95%CI, 0.81-1.09; P = .42). Similarly, pravastatin treatment was not associated with a reduced adjusted risk for incident disease compared with usual hyperlipidemia treatment (HR, 1.13; 95%CI, 0.95-1.35; P = .18). Increased age (HR, 1.47; 95% CI, 1.34-1.63; P <.001), male sex (HR, 0.59; 95%CI, 0.50-0.73; P <.001), white race (HR, 0.59; 95%CI, 0.50-0.70; P <.001), diabetes (HR, 1.23; 95%CI, 1.07-1.42; P = .003), and left ventricular hypertrophy (HR, 3.20; 95%CI, 2.61-3.94; P <.001) were also independently associated with increased risk for conduction system disease. Conclusions and Relevance: Incident conduction system disease is significantly reduced by lisinopril therapy and is independently associated with multiple clinical factors. Further studies are warranted to determine whether pharmacologic treatment affects conduction abnormality outcomes, including pacemaker implantation.

AB - Importance: Cardiac conduction abnormalities are associated with an increased risk for morbidity and mortality, and understanding factors that accelerate or delay conduction system disease could help to identify preventive and therapeutic strategies. Antifibrotic and anti-inflammatory properties of angiotensin-converting enzyme inhibitors and treatment for hyperlipidemia may reduce the risk for incident conduction system disease. Objective: To identify the effect of pharmacologic therapy randomization and clinical risk factors on the incidence of conduction system disease. Design, Setting, and Participants: This secondary analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) investigation acquired data from 623 North American centers. A total of 21 004 ambulatory individuals 55 years or older with hypertension and at least 1 other cardiac risk factor were included in the analysis. Interventions: Participants were randomly assigned to receive amlodipine besylate, lisinopril, or chlorthalidone. Individuals with elevated fasting low-density lipoprotein cholesterol levels were also randomized to pravastatin sodium vs usual care. Main Outcomes and Measures: An electrocardiogram (ECG) was obtained at study enrollment and every 2 years of follow-up. The development of incident first-degree atrioventricular block, left anterior fascicular block, incomplete left bundle branch block (LBBB), LBBB, incomplete right bundle branch block (RBBB), RBBB, or intraventricular conduction delay was assessed by serial ECGs. Results: The 21 004 participants (11 758 men [56.0%]; 9246 women [44.0%]; mean [SD] age, 66.5 [7.3] years) underwent a mean (SD) follow-up of 5.0 (1.2) years. Among the 1114 participants who developed any conduction defect, 389 developed LBBB, 570 developed RBBB, and 155 developed intraventricular conduction delay. Compared with chlorthalidone, randomization to lisinopril was associated with a significant 19% reduction in conduction abnormalities (hazard ratio [HR], 0.81; 95%CI, 0.69-0.95; P = .01). Treatment with amlodipine, however, was not associated with a significant difference in conduction outcome events (HR, 0.94; 95%CI, 0.81-1.09; P = .42). Similarly, pravastatin treatment was not associated with a reduced adjusted risk for incident disease compared with usual hyperlipidemia treatment (HR, 1.13; 95%CI, 0.95-1.35; P = .18). Increased age (HR, 1.47; 95% CI, 1.34-1.63; P <.001), male sex (HR, 0.59; 95%CI, 0.50-0.73; P <.001), white race (HR, 0.59; 95%CI, 0.50-0.70; P <.001), diabetes (HR, 1.23; 95%CI, 1.07-1.42; P = .003), and left ventricular hypertrophy (HR, 3.20; 95%CI, 2.61-3.94; P <.001) were also independently associated with increased risk for conduction system disease. Conclusions and Relevance: Incident conduction system disease is significantly reduced by lisinopril therapy and is independently associated with multiple clinical factors. Further studies are warranted to determine whether pharmacologic treatment affects conduction abnormality outcomes, including pacemaker implantation.

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