Cardiac and Cardiovascular Safety Assessments



The prospective exclusion of unacceptable cardiac and cardiovascular risk has become a critical component of drug safety evaluation in new drug development. At the end of Chapter 4 we discussed the cardiac safety evaluations conducted in a nonclinical research program that are specifically focused on assessing if the drug molecule may impact the hERG current flowing through hERG ion channels and hence lead to QT interval prolongation (or shortening). In this chapter discussions focus on analogous evaluations in humans if a sponsor decides to move the drug molecule into clinical trials. At this point, the term investigational drug can be adopted.


Major Adverse Cardiovascular Event Investigational Drug Regulatory Interest Unacceptable Risk Regulatory Concern 
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Further Readings

  1. Beasley CM Jr, Dmitrienko A, Mitchell MI, 2008, Design and analysis considerations for thorough QT studies employing conventional (10s, 12-lead) ECG recordings, Expert Review in Clinical Pharmacology, 1:815–839.CrossRefGoogle Scholar
  2. Caveney E, Turner JR, 2010, Regulatory landscapes for future antidiabetic drug development (Part I): FDA guidance on assessment of cardiovascular risk. Journal for Clinical Studies, January issue, 34–36.Google Scholar
  3. Turner JR, Durham, 2009, Integrated Cardiac Safety: Assessment Methodologies for Non-cardiac Drugs in Discovery, Development, and Postmarketing Surveillance. Hoboken, NJ: Wiley.Google Scholar
  4. Vaibhav S, Karnard DR, Panicker GP, Kothari S, 2009, Update on the evaluation of a new drug for effects on cardiac repolarization in humans: Issues in early drug development. British Journal of Pharmacology, 159:34–38.Google Scholar
  5. Turner JR, Durham TA, 2009, Integrated Cardiac Safety: Assessment Methodologies for Noncardiac Drugs in Discovery, Development, and Postmarketing Surveillance. Hoboken, NJ: Wiley.Google Scholar
  6. Nissen SE, Wolski K, 2007, Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. New England Journal of Medicine, 356: 2,457–2,471.CrossRefGoogle Scholar
  7. Rock EP, Finkle J, Fingert HJ, et al., 2009, Assessing proarrhythmic potential of drugs when optimal studies are infeasible. American Heart Journal, 157:827–836.PubMedCrossRefGoogle Scholar
  8. Borer JS, Pouleur H, Abadie E, et al., 2007, Cardiovascular safety of drugs not intended for cardiovascular use: Need for a new conceptual basis for assessment and approval. European Heart Journal, 28:1904–1909.PubMedCrossRefGoogle Scholar
  9. Whitehead A, 2002, Meta-analysis of Controlled Clinical Trials. Hoboken, NJ: Wiley.CrossRefGoogle Scholar
  10. Brass EP, Lewis RJ, Lipicky R, Murphy J, Hiatt WR, 2006, Risk assessment in drug development for symptomatic indications: A framework for the prospective exclusion of unacceptable cardiovascular risk. Clinical Pharmacology and Therapeutics, 75:165–172.Google Scholar
  11. De Ponti F, 2008, Pharmacological and regulatory aspects of QT prolongation. In Vaz RJ, Klabunde T (Eds), Antitargets: Prediction and Prevention of Drug Side Effects. Weinheim, Germany: Wiley-VCH.Google Scholar
  12. Morganroth J, Brozovich FV, McDonald JT, Jacobs RA, 1991, Variability of the QT measurement in health men: With implications for selection of an abnormal QT value to predict drug toxicity and proarrhythmia. American Journal of Cardiology, 67:774–776.PubMedCrossRefGoogle Scholar
  13. Diamond GA, Bax L, Kaul S, 2007, Perspective: Uncertain effects of rosiglitazone on the risk for myocardial infarction and cardiovascular death. Annals of Internal Medicine, 147:578–581.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Cardiac Safety Services QuintilesDurhamUSA

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