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Drug Insight: If inhibitors as specific heart-rate-reducing agents

An Erratum to this article was published on 01 April 2006

Abstract

Heart rate is determined primarily by spontaneously repeating net inward current carried by sodium ions and potassium ions through hyperpolarization-activated cyclic-nucleotide-gated channels. Within the heart, these channels are found most abundantly in sinoatrial cardiomyocytes. The channels open in response to membrane hyperpolarization, modulated by local cAMP concentrations. They permit activation of the If current, which can be blocked specifically by molecules characterized by linked benzazepinone and benzocyclobutane rings, and which are devoid of effects on cardiac conduction, inotropy or peripheral vascular tone. The resulting heart-rate reduction has been effective in angina prevention in clinical trials involving 4,000 patients, using the prototype If inhibitor, ivabradine. No serious adverse events have been attributed to the treatment; the most prominent side-effect is dose-related, always reversible and often transient visual symptoms that seldom result in voluntary drug discontinuation.

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Figure 1: Main properties of f-channel inhibition by ivabradine
Figure 2: Effect of ivabradine on time to angina sufficient to limit continued bicycle exercise among 257 protocol-compliant patients with coronary artery disease
Figure 3: Changes in heart rate in the different treatment groups during double-blind dose-ranging

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Correspondence to Jeffrey S Borer.

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JS Borer serves as a paid consultant to Servier Laboratoires, Neuilly sur Seine, France.

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Borer, J. Drug Insight: If inhibitors as specific heart-rate-reducing agents. Nat Rev Cardiol 1, 103–109 (2004). https://doi.org/10.1038/ncpcardio0052

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