What is the clinical evidence from this study?

Study design: Other. Intervention: Ivabradine vs. Atenolol and saline. Primary outcome: Rate and extent of LV relaxation (time constant tau(BF), pressure asymptote P(BF)).

February 1, 2002

Differential effects of heart rate reduction and β-blockade on left ventricular relaxation during exercise

Key Result

Ivabradine, in contrast with atenolol, did not impede the shortening of left ventricular relaxation time during exercise (15 +/- 2 ms vs 23 +/- 2 ms) for a similar heart rate reduction.

Structured PICO

Does ivabradine compared to atenolol affect left ventricular relaxation during exercise in dogs?

Population

Eight chronically instrumented dogs evaluated at rest and during exercise to compare the effects of ivabradine and atenolol on left ventricular relaxation.

Intervention

Increasing doses of ivabradine

Comparator

Atenolol and saline

Outcome

Rate and extent of left ventricular relaxation (time constant tau(BF), pressure asymptote P(BF)) at rest and during exercisesurrogate

In a canine model, ivabradine reduces heart rate without the negative lusitropic effects on left ventricular relaxation seen with atenolol during exercise.

Main Result

Absolute Event Rate: 15% vs 23%

Abstract

Left ventricular (LV) relaxation is crucial for LV function, especially during exercise. We compared the effects of increasing doses of ivabradine, a selective inward hyperpolarization-activated current inhibitor, and atenolol on the rate and extent of LV relaxation (best fit method: time constant tau(BF), pressure asymptote P(BF)) at rest and during exercise. Eight dogs were chronically instrumented to measure LV pressure and LV wall stresses. During exercise under saline, heart rate increased from 108 +/- 5 to 220 +/- 6 beats/min and tau(BF) was significantly reduced from 22 +/- 1 to 14 +/- 2 ms. At rest, atenolol but not ivabradine increased tau(BF). For similar heart rate reductions during exercise, atenolol impeded the shortening of tau(BF) (23 +/- 2 ms) whereas ivabradine had no effect (15 +/- 2 ms). The extent of the relaxation process (P(BF)) at peak exercise was increased by ivabradine, and to a greater extent by atenolol, compared with saline. Thus, for a similar reduction in heart rate at rest and during exercise, ivabradine, in contrast with atenolol, does not exert any negative lusitropic effect.

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