Abstract
In cardiovascular disease, drugs are targeted toward normalizing a single risk factor, the on-target effect. The ultimate goal of drug treatment is to provide long-term cardiovascular organ protection. In recent years, several trials have shown that drugs with promising effects on the on-target risk factor failed to improve long-term cardiovascular protection. One explanation for these failures is that a drug does not only affect the risk factor to which it is targeted but also other parameters, off-target effects, which may also affect long-term cardiovascular outcomes. The drug effect on these off-target effects may be as large or even larger than the on-target effect. The off-target drug effects may consequently have an important impact on the drug effect on cardiovascular outcomes.
This chapter provides an overview of on-target and off-target effects of drugs used in cardiovascular risk management. Keynote in this chapter is that ignoring off-target effects of a drug may lead to severe misinterpretations about the long-term cardiovascular protective effect, with major consequences for society and individual patients. To solve this problem, all effects of a drug should be incorporated into a risk algorithm to obtain a more accurate estimation of the drug effect on long-term cardiovascular outcome.
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Abbreviations
- ACEi:
-
Angiotensin-converting-enzyme inhibitor
- ADVANCE:
-
Action in diabetes and vascular disease: preterax and diamicron MR-controlled evaluation
- ALTITUDE:
-
Aliskiren trial in type 2 diabetes using cardiorenal end points
- ARB:
-
Angiotensin receptor blocker
- DRI:
-
Direct renin inhibitor
- HDL-C:
-
High-density lipoprotein cholesterol
- hs-CRP:
-
High-sensitivity C-reactive protein
- IDNT:
-
Irbesartan diabetic nephropathy trial
- LDL-C:
-
Low-density lipoprotein cholesterol
- NT-proBNP:
-
N-terminal pro-braintype natriuretic peptide
- PRE score:
-
Parameter response efficacy score
- RAAS:
-
Renin-angiotensin-aldosterone system
- RENAAL:
-
Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan study
- UKPDS:
-
UK Prospective Diabetes Study
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Smink, P.A., Heerspink, H.L.J. (2016). Use of Multiple Biomarkers to Estimate Cardiovascular Drug Efficacy: Advantage of a PRE Score. In: Patel, V., Preedy, V. (eds) Biomarkers in Cardiovascular Disease. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7678-4_47
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DOI: https://doi.org/10.1007/978-94-007-7678-4_47
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