Antihypertensives and Incident Conduction System Disease: What’s the Link?

WASHINGTON, DC—At the ACC.17 Scientific Session, Peter M. Okin, from Weill Cornell Medicine, New York, NY, reported that incident intraventricular conduction delay (IVCD)—but not bundle branch block (BBB)—was significantly reduced by losartan-based treatment. 

Earlier research has shown lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, reduced the incidence of a composite conduction system disease endpoint and also left BBB when compared to amlodipine or chlorthalidone therapy. However, the association between incident conduction system disease and angiotensin receptor blocker (ARB) therapy has not been studied, Okin explained. 

Okin and study authors aimed to assess the relationship of incident LBBB, right BBB (RBBB), and non-specific IVCD to losartan- vs. atenolol-based therapy and to determine whether any potential relationship to the risk of new conduction system disease is independent of the prognostic value of other statistically significant predictors of incident conduction system disease in the subset of the LIFE (Losartan Intervention For Endpoint reduction in hypertension) study population,” described Okin. 

In the study, 8342 hypertensive patients without baseline RBBB or LBBB in relation to losartan- vs. atenolol-based treatment were examined. “Risk of incident IVCD, defined as new QRS duration ≥110ms was assessed in the patient subset who also had baseline QRS duration <110ms. QRS duration and BBB were determined on in-study ECGs done at 6 months, 1 year and then yearly.” 

Patients were followed up for median 4.8 years, in which 459 (5.5%) patients developed new LBBB, 184 (2.25%) developed new RBBB, and 1173 (15.2%) developed a new IVCD. Findings from the univariate Cox analyses showed that losartan-based treatment was not associated with a significantly reduced risk of either new LBBB (hazard ratio [HR] 0.95, 95% CI: 0.79–1.14; P=0.583) or RBBB (HR 1.02, 95% CI: 0.76–1.36; P=0.903). 

Findings from the multivariable Cox model that adjusted for statistically significant predictors of incident IVCD in this patient population showed that losartan-based treatment was associated with a 13% reduced risk of new IVCD (HR 0.87, 95% CI: 0.77–0.98; P=0.021). Predictors of incident IVCD included: age, sex, race, history of ischemic heart disease, MI, heart failure, diabetes or atrial fibrillation, prior antihypertensive treatment, baseline total and HDL cholesterol, serum glucose and creatinine and baseline QRS duration as standard covariates and incident MI and on-treatment systolic and diastolic pressure, body mass index, and Cornell voltage as time-dependent covariates.

In conclusion, losartan-based treatment was associated with a significant reduction in incident IVCD but not BBB. This risk of new IVCD development was “independent of other univariate predictors of QRS prolongation overtime, including baseline QRS duration and the impact of changing levels of systolic and diastolic blood pressure andCornell voltage LVH during treatment,” added Okin. “Further study is warranted to assess the potential differential impact of this therapy on QRS prolongation vs. development of more discrete conduction system block.”