Clinical Pharmacodynamics of Cardiovascular Agents: Focus on Sudden Cardiac Death

  • Dan M. Roden

Abstract

Sudden death due to ventricular tachyarrhythmias is common in patients with advanced coronary artery disease. Three strategies might be useful: slowing progression of coronary atherosclerosis (e.g. antihypertensive or lipid-lowering agents); antiarrhythmic therapy; or elimination of transient factors which trigger fatal arrhythmias (e.g. antiplatelet drugs or ß-blockers). For each of these classes of compounds, an easily measured response variable, such as heart rate, blood pressure, ECG interval, frequency of ambient arrhythmia, or bleeding time, is available and the links between drug concentrations and response are readily determined. However, the common extrapolation that these responses are necessarily accompanied by a decrease in sudden death is unfounded. In addition, patients who are at risk for sudden death have an underlying cardiac substrate which can fluctuate over seconds to years, resulting in both loss of drug efficacy and increased drug toxicity. Thus evaluation of interventions designed to reduce sudden death must be performed in patients at risk, using death as the study end-point. This approach also permits assessment of compounds whose only therapeutic action might be to reduce sudden death.

Keywords

Sudden Death Parent Drug Antiarrhythmic Drug Poor Metabolizers Antiarrhythmic Therapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Dan M. Roden
    • 1
  1. 1.Departments of Medicine and PharmacologyVanderbilt University School of MedicineNashvilleUSA

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