505diphosphate (ADP) P2Y12 receptor on platelets for their lifespan, thereby inhibit-
ing their activation and decreasing subsequent platelet aggregation. Hydrolysis by
intestinal carboxylesterases and oxidation by intestinal and hepatic cytochrome
P-450 enzymes convert prasugrel into its active metabolite. Prasugrel has a greater
antiplatelet effect than clopidogrel because it is metabolized more effi ciently.
Genetic polymorphisms affecting the cytochrome P450 system may explain some
of the differences in metabolism between prasugrel and clopidogrel.
Resistance to clopidogrel, an antiplatelet therapy, has been shown to be present
in 25–30 % of Caucasians and an even higher percentage in Asians. Part of this
resistance is because of the CYP2C192 allele. CYP2C19 variant alleles are inde-
pendent predictors of clopidogrel response variability and occurrence of major
adverse cardiovascular events in high-risk vascular patients on clopidogrel therapy.
Increasing evidence suggests a combination of platelet function testing with
CYP2C19 genetic testing may be more effective in identifying high-risk individuals
for alternative antiplatelet therapeutic strategies. A crucial point in evaluating the
use of these polymorphisms in clinical practice, besides test accuracy, is the cost of
the genetic test and rapid availability of the results. One study has genotyped 100
acute coronary syndrome patients for CYP2C192,3,4,5, and 17 polymor-
phisms with two platforms: Verigene® and the TaqMan® system (Saracini et al.
2012 ). Genotyping results obtained by the classical TaqMan approach and the rapid
Verigene approach showed a 100 % concordance for all the fi ve polymorphisms
investigated. The Verigene system had shorter turnaround time with respect to
TaqMan. The cost of reagents for TaqMan genotyping was lower than that for the
Verigene system, but the effective staff involvement and the relative cost resulted in
higher cost for TaqMan than for Verigene. In conclusion, Verigene system demon-
strated good performance in terms of turnaround time and cost for the evaluation of
the clopidogrel poor metabolizer status, giving genetic information in suitable time
(<2.5 h) for a therapeutic strategy decision.
Genetic testing for aspirin resistance is not yet recommended because of incom-
plete genetic data. Studies to determine the value of genetic testing before the
administration of warfarin are ongoing. Testing for SLCO1B1 allele in individuals
with muscle cramps who are taking statins could be very helpful but is not yet rec-
ommended as a routine.
Nanobiotechnology-Based Personalized Therapy
of Cardiovascular Diseases
The future of cardiovascular diagnosis already is being impacted by nanosystems
that can both diagnose pathology and treat it with targeted delivery systems. The
potential dual use of nanoparticles for both imaging and site-targeted delivery of
therapeutic agents to cardiovascular disease offers great promise for individualizing
therapeutics. Image-based therapeutics with site-selective agents should enable ver-
ifi cation that the drug is reaching the intended target and a molecular effect is occur-
ring. Experimental studies have shown that binding of paclitaxel to smooth muscle
Role of Diagnostics in Personalized Management of Cardiovascular Disease