aliskiren and Long-QT-Syndrome

To evaluate the effect of aliskiren compared to amlodipine on QT duration and dispersion in hypertensive patients with type 2 diabetes.. A total of 170 outpatients aged 50-75 years with mild to moderate hypertension (SBP >130 and <180 mmHg and DBP >80 and <100 mmHg) and type 2 diabetes were randomly treated with aliskiren 300 mg or amlodipine 10 mg, both given once daily for 24 weeks, according to a prospective, open label, blinded-end point, parallel group design. At the end of the placebo run-in, and after 12, and 24 weeks of treatment blood pressure (BP) measurements (by mercury sphygmomanometer, Korotkoff I and V), plasma biochemistry and a standard 12-lead surface ECG were evaluated.. Both aliskiren and amlodipine significantly reduced systolic blood pressure (SBP)/diastolic blood pressure (DBP) values (-27.2/-14.3 mmHg, p < 0.001 vs. placebo and -27.8/-14.2 mmHg, p < 0.001 vs. placebo, respectively), with no statistical difference between the two drugs. Aliskiren, but not amlodipine, significantly reduced maximum QT interval (QTmax) (-14 ms at 12 weeks and -17 ms at 24 weeks, both p < 0.05 vs. placebo) and corrected QT max (QTc max) (-26 ms and -31 ms, p < 0.01) as well as the dispersion of both QT (-11 ms and -13 ms, p < 0.01) and QTc (-18 ms and -19 ms, p < 0.01).. Despite similar BP lowering effect, aliskiren, but not amlodipine, reduced QT duration and dispersion, which might be related to the ability of aliskiren to interfere with mechanisms underlying myocardial electrical instability in the heart of diabetic hypertensive patients.

Topics: Aged; Amides; Amlodipine; Antihypertensive Agents; Blood Pressure; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Electrocardiography; Female; Fumarates; Heart Conduction System; Humans; Hypertension; Long QT Syndrome; Male; Middle Aged; Prospective Studies

Topics: Amides; Anti-Arrhythmia Agents; Antihypertensive Agents; Fumarates; Humans; Long QT Syndrome; Sotalol

Aliskiren gained FDA approval for the treatment of hypertension in 2007. It is the first approved pharmaceutical to manage hypertension by direct renin inhibition. With the introduction of novel drugs and mechanisms of action comes the challenge of monitoring for new unreported adverse events. The side effect profile for aliskiren has not yet been fully described. We describe the first apparent report of aliskiren-induced QT prolongation resulting in torsades de pointes.

Topics: Aged; Amides; Anti-Arrhythmia Agents; Antihypertensive Agents; Female; Fumarates; Humans; Long QT Syndrome; Sotalol