Effect of antihypertensive therapy on development of incident conduction system disease in hypertensive patients

Previous work has demonstrated that treatment of hypertensive patients with the angiotensin-converting enzyme inhibitor lisinopril was associated with a reduced incidence of a composite conduction system disease endpoint and also left bundle branch block (LBBB) compared with chlorthalidone therapy. The relationship of incident conduction system disease to angiotensin receptor blocker therapy has not been examined.

Risk of new right (RBBB) or LBBB in relation to losartan-based vs. atenolol-based treatment was assessed in 8342 hypertensive patients without baseline RBBB or LBBB. Risk of incident intraventricular conduction delay (IVCD), defined as new QRS duration at least 110 ms was assessed in the 7110 patient subset who also had baseline QRS duration less than 110 ms. QRS duration and BBB were determined on in-study ECGs done at 6 months, 1 year and then yearly.

During 4.8 ± 1.0 years follow-up, 459 patients developed new LBBB (5.5%), 184 (2.2) new RBBB and 1173 (16.5%) a new IVCD. In univariate Cox analyses, losartan-based treatment was not associated with a significantly reduced risk of either new LBBB (hazard ratio 0.95, 95% CI 0.79-1.14, P = 0.583) or RBBB (hazard ratio 1.02, 95% CI 0.76-1.36, P = 0.903), but resulted in a 15% lower risk of new IVCD (hazard ratio 0.85, 95% CI 0.76-0.95, P = 0.005). In a multivariable Cox model that adjusted for other statistically significant predictors of incident IVCD in this population (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, BMI and Cornell voltage as time-dependent covariates), losartan treatment remained associated with a 13% lower risk of new IVCD (hazard ratio 0.87, 95% CI 0.77-0.98, P = 0.021).

Incident IVCD, but not BBB, is significantly reduced by losartan-based treatment. Further study is warranted to assess the potential differential impact of this therapy on QRS prolongation vs. development of more discrete conduction system block.

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