Economic evaluation of pharmacogenomic-guided antiplatelet treatment in Spanish patients suffering from acute coronary syndrome participating in the U-PGx PREPARE study.

BACKGROUND: Cardiovascular diseases and especially Acute Coronary Syndrome (ACS) constitute a major health issue impacting millions of patients worldwide. Being a leading cause of death and hospital admissions in many European countries including Spain, it accounts for enormous amounts of healthcare expenditures for its management. Clopidogrel is one of the oldest antiplatelet medications used as standard of care in ACS. METHODS: In this study, we performed an economic evaluation study to estimate whether a genome-guided clopidogrel treatment is cost-effective compared to conventional one in a large cohort of 243 individuals of Spanish origin suffering from ACS and treated with clopidogrel. Data were derived from the U-PGx PREPARE clinical trial. Effectiveness was measured as survival of individuals while study data on safety and efficacy, as well as on resource utilization associated with each adverse drug reaction were used to measure costs to treat these adverse drug reactions. A generalized linear regression model was used to estimate cost differences for both study groups. RESULTS: Based on our findings, PGx-guided treatment group is cost-effective. PGx-guided treatment demonstrated to have 50% less hospital admissions, reduced emergency visits and almost 13% less ADRs compared to the non-PGx approach with mean QALY 1.07 (95% CI, 1.04-1.10) versus 1.06 (95% CI, 1.03-1.09) for the control group, while life years for both groups were 1.24 (95% CI, 1.20-1.26) and 1.23 (95% CI, 1.19-1.26), respectively. The mean total cost of PGx-guided treatment was 50% less expensive than conventional therapy with clopidogrel [€883 (95% UI, €316-€1582), compared to €1,755 (95% UI, €765-€2949)]. CONCLUSION: These findings suggest that PGx-guided clopidogrel treatment represents a cost-effective option for patients suffering from ACS in the Spanish healthcare setting.

Implementation of pharmacogenomic clinical decision support for health systems: a cost-utility analysis.

We constructed a cost-effectiveness model to assess the clinical and economic value of a CDS alert program that provides pharmacogenomic (PGx) testing results, compared to no alert program in acute coronary syndrome (ACS) and atrial fibrillation (AF), from a health system perspective. We defaulted that 20% of 500,000 health-system members between the ages of 55 and 65 received PGx testing for CYP2C19 (ACS-clopidogrel) and CYP2C9, CYP4F2 and VKORC1 (AF-warfarin) annually. Clinical events, costs, and quality-adjusted life years (QALYs) were calculated over 20 years with an annual discount rate of 3%. In total, 3169 alerts would be fired. The CDS alert program would help avoid 16 major clinical events and 6 deaths for ACS; and 2 clinical events and 0.9 deaths for AF. The incremental cost-effectiveness ratio was $39,477/QALY. A PGx-CDS alert program was cost-effective, under a willingness-to-pay threshold of $100,000/QALY gained, compared to no alert program.

Cost-effectiveness of CYP2C19-guided antiplatelet therapy for acute coronary syndromes in Singapore.

We evaluated the cost-effectiveness of a genotype-guided strategy among patients with acute coronary syndromes using a decision-tree model based on the Singapore healthcare payer's perspective over a 1-year time horizon. Three dual antiplatelet strategies were considered: universal clopidogrel, genotype-guided, and universal ticagrelor. The prevalence of loss-of-function alleles was assumed to be 61.7% and model inputs were identified from the literature. Our primary outcome of interest was incremental cost-effectiveness ratio (ICER) compared to universal clopidogrel. Both genotype-guided (72,158 SGD/QALY) and universal ticagrelor (82,269 SGD/QALY) were considered cost-effective based on a willingness-to-pay (WTP) threshold of SGD 88,991. In our secondary analysis, the ICER for universal ticagrelor was 114,998 SGD/QALY when genotype-guided was taken as a reference. Probabilistic sensitivity analysis revealed that genotype-guided was the most cost-effective strategy when the WTP threshold was between SGD 70,000 to 100,000. Until more data are available, our study suggests that funding for a once-off CYP2C19 testing merits a consideration over 1 year of universal ticagrelor.

Cost-effectiveness of CYP2C19-guided antiplatelet therapy in patients with acute coronary syndrome and percutaneous coronary intervention informed by real-world data.

Current guidelines recommend dual antiplatelet therapy (DAPT) consisting of aspirin and a P2Y12 inhibitors following percutaneous coronary intervention (PCI). CYP2C19 genotype can guide DAPT selection, prescribing ticagrelor or prasugrel for loss-of-function (LOF) allele carriers (genotype-guided escalation). Cost-effectiveness analyses (CEA) are traditionally grounded in clinical trial data. We conduct a CEA using real-world data using a 1-year decision-analytic model comparing primary strategies: universal empiric clopidogrel (base case), universal ticagrelor, and genotype-guided escalation. We also explore secondary strategies commonly implemented in practice, wherein all patients are prescribed ticagrelor for 30 days post PCI. After 30 days, all patients are switched to clopidogrel irrespective of genotype (nonguided de-escalation) or to clopidogrel only if patients do not harbor an LOF allele (genotype-guided de-escalation). Compared with universal clopidogrel, both universal ticagrelor and genotype-guided escalation were superior with improvement in quality-adjusted life years (QALY's). Only genotype-guided escalation was cost-effective ($42,365/QALY) and demonstrated the highest probability of being cost-effective across conventional willingness-to-pay thresholds. In the secondary analysis, compared with the nonguided de-escalation strategy, although genotype-guided de-escalation and universal ticagrelor were more effective, with ICER of $188,680/QALY and $678,215/QALY, respectively, they were not cost-effective. CYP2C19 genotype-guided antiplatelet prescribing is cost-effective compared with either universal clopidogrel or universal ticagrelor using real-world implementation data. The secondary analysis suggests genotype-guided and nonguided de-escalation may be viable strategies, needing further evaluation.

Cost-effectiveness of CYP2C19 LOF-guided antiplatelet therapy in Chinese patients with acute coronary syndrome.

Aim: This study aimed to evaluate the cost-effectiveness of CYP2C19 loss-of-function(LOF) allele-guided antiplatelet therapy compared with the universal use of clopidogrel or ticagrelor among Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention. Methods: A two-part cost-effectiveness model comprising of a 1-year decision tree and a long-term Markov model was utilized to simulate outcomes of three treatment strategies: universal use of clopidogrel (75 mg daily) or universal use of ticagrelor 90 mg twice daily for all patients and CYP2C19 LOF-guided therapy (LOF allele carriers receiving ticagrelor, LOF allele noncarriers receiving clopidogrel). Model outcomes included quality-adjusted life years (QALYs) gained, direct medical costs and incremental cost-effectiveness ratios (ICERs). ICERs less than one-time gross domestic product per capita in China 59,660 yuan/QALY were considered cost-effective. Results: Base-case analysis showed 'universal ticagrelor use' was cost-effective for an ICER of 33,875 yuan per QALY gained compared with 'universal clopidogrel use' of which gained a 1.6932 QALYs at lowest life-long cost of 2450 yuan. CYP2C19 LOF-guided therapy had an effectiveness of 1.6975 QALYs at a cost of 2812 yuan, for an ICER of 84,118 yuan per QALY gained relative to 'universal clopidogrel use'. Sensitivity analysis demonstrated that base-case results were significantly affected by five factors: the risk ratio of 'non-fatal myocardial infarction', 'non-fatal stroke' and 'cardiovascular death' in ticagrelor versus clopidogrel and the annual costs of clopidogrel and ticagrelor. According to the results of Monte Carlo simulation, when willing to pay is about 32,000 yuan, patients willing to receive clopidogrel or ticagrelor are approximately equal. Conclusion: Optimal antiplatelet treatment is affected by lots of factors. The results of our study demonstrated that 'universal ticagrelor use' was cost-effective compared with 'universal clopidogrel use' for Chinese acute coronary syndrome patients with percutaneous coronary intervention.

An Evaluation of the Cost-effectiveness of Comprehensive MTM Integrated with Point-of-Care Phenotypic and Genetic Testing for U.S. Elderly Patients After Percutaneous Coronary Intervention.

BACKGROUND: Poor health outcomes after percutaneous coronary intervention (PCI) in elderly patients is an area of concern among policymakers and administrators. In an effort to determine the best strategy to improve outcomes among elderly patients who underwent PCI, several studies have evaluated the cost-effectiveness of genotype-guided antiplatelet therapy compared with universal use of any one of the antiplatelet drugs indicated for patients with acute coronary syndrome (ACS) who underwent PCI. The results have either been in favor of genotype-guided antiplatelet therapy or universal use of ticagrelor. However, no study has yet evaluated the cost-effectiveness of pharmacist-provided face-to-face medication therapy management (MTM) combined with point-of-care genotype-guided antiplatelet therapy (POCP) when compared with universal use of ticagrelor or clopidogrel for the elderly after PCI. OBJECTIVE: To evaluate the cost-effectiveness of a pharmacist integration of MTM with POCP (MTM-POCP) when compared with universal use of ticagrelor or clopidogrel combined with MTM (MTM-ticagrelor or MTM-clopidogrel). METHODS: We conducted a cost-effectiveness analysis from the perspective of the U.S. health care system. A hybrid model, consisting of a 1-year decision tree and a 20-year Markov model, was used to simulate a cohort of elderly patients (aged at least 65 years) with ACS who underwent PCI. Treatment strategies available to patients were POCP, POCP-MTM, MTM-clopidogrel, or MTM-ticagrelor. Data used to populate the model were obtained from the PLATO trial and other published studies. Outcome measures were costs, quality-adjusted life-years (QALYs) and incremental cost per QALY gained. A deterministic and probabilistic sensitivity analysis was conducted to account for the joint uncertainty around the key parameters of the model. Finally, a benchmark willingness to pay of $50,000-200,000 was considered. RESULTS: The use of PCOP (with dual antiplatelet therapy) resulted in 5.29 QALYs, at a cost of $50,207. MTM-clopidogrel resulted in 5.34 QALYs, at a cost of $50,011. The use of POCP-MTM resulted in 5.36 QALYs, at a cost of $50,270. Finally, MTM-ticagrelor resulted in 5.42 QALYs, at a cost of $53,346. MTM-ticagrelor was found to be cost-effective compared with MTM-clopidogrel or MTM-POCP, irrespective of the willingness to pay. The deterministic and probabilistic sensitivity analyses confirmed the robustness of the base-case analysis. CONCLUSIONS: The combination of MTM-ticagrelor was cost-effective when compared with MTM-POCP or MTM-clopidogrel. The transitional probabilities, however, were mostly based on published studies. Analysis based on a prospective randomized clinical study, comparing all the treatment strategies included in this study, is warranted to confirm our findings. DISCLOSURES: No outside funding supported this study. The authors have no conflicts of interest to declare. Study concept and design were contributed by Okere and Diaby. Ezendu took the lead in data collection, along with Okere. Data interpretation was performed by all the authors. The manuscript was written by Okere, Diaby, and Berthe and revised by Okere and Diaby.

Cost-effectiveness of cytochrome P450 2C19 *2 genotype-guided selection of clopidogrel or ticagrelor in Chinese patients with acute coronary syndrome.

The choice of antiplatelet therapy among Asian populations for the treatment of acute coronary syndrome (ACS) is complicated owing to the high prevalence of cytochrome P450 2C19 (CYP2C19) genetic polymorphism that has been associated with reduced efficacy of clopidogrel. Ticagrelor is a potent but more expensive alternative antiplatelet agent that is not affected by CYP2C19 polymorphism. This study aimed to evaluate the cost-effectiveness, from the Hong Kong health-care provider's perspective, of CYP2C19*2 genotype-guided selection of antiplatelet therapy compared with the universal use of clopidogrel or ticagrelor among ACS patients who undergo percutaneous coronary intervention (PCI). In the present study, a two-part model consisting of a 1-year decision tree and a lifetime Markov model was built to simulate the progress of a typical cohort of 60-year-old Chinese patients until age 85 years and compare three treatment strategies: (i) generic clopidogrel or ticagrelor based on CYP2C19*2 genotype, (ii) universal use of generic clopidogrel or (iii) universal use of ticagrelor for all patients. Incremental cost-effectiveness ratios (ICERs) of <1 gross domestic product per capita locally (US dollar (USD)42 423/quality-adjusted life year (QALY)) were considered cost-effective. Base-case results showed universal ticagrelor use was cost-effective compared with universal clopidogrel, but was dominated by genotype-guided treatment. Genotype-guided treatment was cost-effective compared with universal clopidogrel use (ICER of USD2560/QALY). Sensitivity analysis demonstrated that with the cost of genotype testing up to USD400, CYP2C19*2 genotype-guided antiplatelet treatment remained a cost-effective strategy compared with either universal use of generic clopidogrel or ticagrelor in post-PCI ACS patients in Hong Kong.

Assessment of the rs4340 ACE gene polymorphism in acute coronary syndrome in a Western Mexican population.

Acute coronary syndrome (ACS) is considered one of the main causes of death worldwide. Contradictory findings concerning the impact of the angiotensin-converting enzyme (ACE) gene on cardiovascular diseases have been reported. Previous conclusions point out that the variability in results depends on ethnicity and genetic polymorphisms to determine the association of rs4340 polymorphisms of the ACE gene and ACE circulating levels in ACS. Genotyping of rs4340 polymorphisms was performed in a total of 600 individuals from Western Mexico divided into two groups: the ACS and the control group (CG). The polymorphisms were identified by polymerase chain reaction. Serum ACE concentration was determined by enzyme-linked immunosorbent assay. D/D carriers had higher ACE levels than I/I carriers (3.6 vs 2.8 ng/mL, P < 0.0021) in the CG. The D/D genotype of the rs4340 polymorphism is associated with higher ACE concentration levels; however, the polymorphism was not associated with ACS.

CYP2C19 LOF and GOF-Guided Antiplatelet Therapy in Patients with Acute Coronary Syndrome: A Cost-Effectiveness Analysis.

PURPOSE: This study aimed to examine the cost-effectiveness of CYP2C19 loss-of-function and gain-of-function allele guided (LOF/GOF-guided) antiplatelet therapy in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). METHODS: A life-long decision-analytic model was designed to simulate outcomes of three strategies: universal clopidogrel (75 mg daily), universal alternative P2Y12 inhibitor (prasugrel 10 mg daily or ticagrelor 90 mg twice daily), and LOF/GOF-guided therapy (LOF/GOF allele carriers receiving alternative P2Y12 inhibitor, wild-type patients receiving clopidogrel). Model outcomes included clinical event rates, quality-adjusted life-years (QALYs) gained and direct medical costs from perspective of US healthcare provider. RESULTS: Base-case analysis found nonfatal myocardial infarction (5.62%) and stent thrombosis (1.2%) to be the lowest in universal alternative P2Y12 inhibitor arm, whereas nonfatal stroke (0.72%), cardiovascular death (2.42%), and major bleeding (2.73%) were lowest in LOF/GOF-guided group. LOF/GOF-guided arm gained the highest QALYs (7.5301 QALYs) at lowest life-long cost (USD 76,450). One-way sensitivity analysis showed base-case results were subject to the hazard ratio of cardiovascular death in carriers versus non-carriers of LOF allele and hazard ratio of cardiovascular death in non-carriers of LOF allele versus general patients. In probabilistic sensitivity analysis of 10,000 Monte Carlo simulations, LOF/GOF-guided therapy, universal alternative P2Y12 inhibitor, and universal clopidogrel were the preferred strategy (willingness-to-pay threshold = 50,000 USD/QALY) in 99.07%, 0.04%, and 0.89% of time, respectively. CONCLUSIONS: Using both CYP2C19 GOF and LOF alleles to select antiplatelet therapy appears to be the preferred antiplatelet strategy over universal clopidogrel and universal alternative P2Y12 inhibitor therapy for ACS patients with PCI.

Cost-effectiveness analysis of personalized antiplatelet therapy in patients with acute coronary syndrome.

AIM: This study aimed to compare the clinical and economic outcomes of pharmacogenetic-guided (PG-guided) and platelet reactivity testing-guided antiplatelet therapy for patients with acute coronary syndrome undergoing percutaneous coronary intervention. METHODS: A decision-analytic model was simulated including four antiplatelet strategies: universal clopidogrel 75 mg daily, universal alternative P2Y12 inhibitor (prasugrel or ticagrelor), PG-guided therapy, and platelet reactivity testing-guided therapy. RESULTS: PG-guided therapy was the preferred option with lowest cost (US$75,208) and highest quality-adjusted life years gained (7.6249 quality-adjusted life years). The base-case results were robust in sensitivity analysis. CONCLUSION: PG-guided antiplatelet therapy showed the highest probability to be preferred antiplatelet strategy for acute coronary syndrome patients with percutaneous coronary intervention.

CYP2C19 genotype plus platelet reactivity-guided antiplatelet therapy in acute coronary syndrome patients: a decision analysis.

OBJECTIVES: We examined the cost-effectiveness of CYP2C19 genotype plus platelet reactivity-guided antiplatelet therapy (PG-PRT) from the perspective of US healthcare providers. METHODS: A decision-analytic model was used to simulate life-long medical costs and quality-adjusted life-years (QALYs) of three antiplatelet strategies in a hypothetical cohort of 60-year-old patients with acute coronary syndrome after a percutaneous coronary intervention: (a) universal clopidogrel (75 mg daily), (b) universal alternative antiplatelet therapy (prasugrel or ticagrelor), and (c) all PG-PRT patients were genotyped. Noncarriers of the CYP2C19 loss-of-function (LOF) allele received clopidogrel 75 mg daily. CYP2C19 LOF allele(s) carriers who were poor metabolizers received prasugrel or ticagrelor. CYP2C19 LOF allele(s) carriers who were intermediate metabolizers (IM) received high-dose clopidogrel (225 mg daily) and were tested for high on-treatment platelet reactivity (HTPR). IM patients with HTPR were switched to prasugrel or ticagrelor. Model inputs were derived from the literature. RESULTS: In base-case analysis, PG-PRT was the least costly (USD 71,887) strategy with highest QALYs gained (7.886 QALYs). Sensitivity analyses found universal clopidogrel to be the preferred strategy if the prevalence of the CYP2C19 LOF allele was less than 2.6% or the incidence of HTPR in IM patients was greater than 82.8%. In 10,000 Monte Carlo simulations, PG-PRT was less costly than universal clopidogrel by USD 91 [95% confidence interval (CI) 83-99; P=0.0499], with higher QALYs by 0.0257 (95% CI: 0.0256-0.0258; P<0.001). Compared with universal alternative antiplatelet therapy, PG-PRT was less costly by USD 2208 (95% CI: 2195-2221; P<0.001) and gained 0.0085 QALYs (95% CI: 0.0083-0.0087; P=0.0260). CONCLUSION: PG-PRT seems to be cost-saving and effective for guiding selection of antiplatelet therapy in acute coronary syndrome patients undergoing percutaneous coronary intervention.

Assessment and diagnostic relevance of novel serum biomarkers for early decision of ST-elevation myocardial infarction.

Blood transcriptome reflects the status of diseases, and characteristic molecular signature provides a novel window on gene expression preceding acute coronary events. We aim to determine blood transcriptome-based molecular signature of acute coronary syndrome (ACS), and to identify novel serum biomarkers for early stage ST-segment-elevation myocardial infarction (STEMI). We obtained peripheral blood from the patients with ACS who visited emergency department within 4 hours after the onset of chest pain: STEMI (n = 10), Non-ST-segment-elevation MI (NSTEMI, n = 10) and unstable angina (UA, n = 11). Blood transcriptome scans revealed that a characteristic gene expression change exists in STEMI, resulting in 531 outlier genes as STEMI molecular signature (Welch's t test, P < 0.05). Another analysis with a set of blood samples of patients with STEMI (n = 7) before and 7 days after the primary percutaneous coronary intervention (n = 7) and normal control (n = 10) evidenced that STEMI molecular signature directly reflects the onset of STEMI pathogenesis. From the two sets of transcriptome-based STEMI signatures, we identified 10 genes encoding transmembrane or secretory proteins that are highly expressed in STEMI. We validated blood protein expression levels of these 10 putative biomarkers in 40 STEMI and 32 healthy subjects by ELISA. Data suggested that PGLYRP1, IRAK3 and VNN3 are more specific and sensitive diagnostic biomarkers for STEMI than traditional CK-MB or troponin.Blood transcriptome scans of ACS evidenced early stage molecular markers for STEMI. Here, we report novel biomarkers to diagnose STEMI at emergency department in hospitals by a simple ELISA method.

Assessment of the E-selectin rs5361 (561A>C) polymorphism and soluble protein concentration in acute coronary syndrome: association with circulating levels.

INTRODUCTION: The acute coronary syndrome (ACS) is a complex disease where genetic and environmental factors are involved. E-selectin gene is a candidate for ACS progression due to its contribution in the inflammatory process and endothelial function. The rs5361 (561A>C) polymorphism in the E-selectin gene has been linked to changes in gene expression, affinity for its receptor, and plasmatic levels; therefore it is associated with an increased risk of cardiovascular disease. The aim of this study was to determine the association of the rs5361 polymorphism with ACS and to measure serum levels of soluble E-selectin (sE-selectin). MATERIALS AND METHODS: 283 ACS patients and 205 healthy subjects (HS) from Western Mexico were included. The polymerase chain reaction-restriction fragment length polymorphism was used to determine the rs5361 polymorphism. The sE-selectin levels were measured by enzyme-linked immunosorbent assay. RESULTS: Neither genotype nor allele frequencies of the rs5361 polymorphism showed statistical differences between groups. The sE-selectin levels were significantly higher in ACS patients compared to HS (54.58 versus 40.41 ng/ml, P = 0.02). The C allele had no effect on sE-selectin levels. CONCLUSIONS: The rs5361 E-selectin gene polymorphism is not a susceptibility marker for ACS in Western Mexico population. However, sE-selectin may be a biological marker of ACS.

Cost-effectiveness of using CYP2C19 genotype to guide selection of clopidogrel or ticagrelor in Australia.

AIMS: This study aims to assess the cost-effectiveness in Australia of screening CYP2C19 loss-of-function (LoF) alleles to guide selection of clopidogrel or ticagrelor for individuals with acute coronary syndrome who are likely to undergo coronary stenting. METHODS: Three treatment strategies were compared: universal clopidogrel therapy, universal ticagrelor therapy and genotyping CYP2C19 with use of ticagrelor for individuals with a LoF allele and clopidogrel for individuals without a LoF allele. Lifetime costs and quality-adjusted life years for each treatment strategy were estimated using a Markov model. The risks of events were primarily derived from the genetic substudy of the pivotal randomized controlled trial. RESULTS: CYP2C19 genotyping resulted in greater effectiveness and was cost-effective when compared with universal use of clopidogrel. However, universal use of ticagrelor was the most effective strategy overall and the incremental cost-effectiveness compared with the genotyping strategy was generally within what is considered acceptable. CONCLUSION: Ticagrelor is likely to be cost-effective even for individuals not carrying a CYP2C19 LoF allele.

Cost effectiveness of targeted high-dose atorvastatin therapy following genotype testing in patients with acute coronary syndrome.

BACKGROUND: Results from the PROVE IT trial suggest that patients with acute coronary syndrome (ACS) treated with atorvastatin 80 mg/day (A80) have significantly lower rates of cardiovascular events compared with patients treated with pravastatin 40 mg/day (P40). In a genetic post hoc substudy of the PROVE IT trial, the rate of event reduction was greater in carriers of the Trp719Arg variant in kinesin family member 6 protein (KIF6) than in noncarriers. We assessed the cost effectiveness of testing for the KIF6 variant followed by targeted statin therapy (KIF6 Testing) versus not testing patients (No Test) and treating them with P40 or A80 in the USA from a payer perspective. METHODS: A Markov model was developed in which 2-year event rates from PROVE IT were extrapolated over a lifetime horizon. Costs and utilities were derived from published literature. All costs were in 2010 US dollars except the cost of A80, which was in 2012 US dollars because the generic formulation was available in 2012. Expected costs and quality-adjusted life-years (QALYs) were estimated for each strategy over a lifetime horizon. RESULTS: Lifetime costs were US$31,700; US$37,100 and US$41,300 for No Test P40, KIF6 Testing and No Test A80 strategies, respectively. The No Test A80 strategy was associated with more QALYs (9.71) than the KIF6 Testing (9.69) and No Test P40 (9.57) strategies. No Test A80 had an incremental cost-effectiveness ratio (ICER) of US$232,100 per QALY gained compared with KIF6 Testing. KIF6 Testing had an ICER of US$45,300 per QALY compared with No Test P40. CONCLUSIONS: Testing ACS patients for KIF6 carrier status may be a cost-effective strategy at commonly accepted thresholds. Treating all patients with A80 is more expensive than treating patients on the basis of KIF6 results, but the modest gain in QALYs is achieved at a cost/QALY that is generally considered unacceptable compared with the KIF6 Testing strategy. Compared with treating all patients with P40, the KIF6 Testing strategy had an ICER below US$50,000 per QALY. The conclusions from this study are sensitive to the price of generic A80 and the effect on adherence of knowing KIF6 carrier status. The results were based on a post hoc substudy of the PROVE IT trial, which was not designed to test the effectiveness of KIF6 testing.

Genetic testing in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a cost-effectiveness analysis.

BACKGROUND: The CYP2C19 genotype is a predictor of adverse cardiovascular events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) treated with clopidogrel. OBJECTIVES: We aimed to evaluate the cost-effectiveness of a CYP2C19*2 genotype-guided strategy of antiplatelet therapy in ACS patients undergoing PCI, compared with two 'no testing' strategies (empiric clopidogrel or prasugrel). METHODS: We developed a Markov model to compare three strategies. The model captured adverse cardiovascular events and antiplatelet-related complications. Costs were expressed in 2010 US dollars and estimated using diagnosis-related group codes and Medicare reimbursement rates. The net wholesale price for prasugrel was estimated as $5.45 per day. A generic estimate for clopidogrel of $1.00 per day was used and genetic testing was assumed to cost $500. RESULTS: Base case analyses demonstrated little difference between treatment strategies. The genetic testing-guided strategy yielded the most QALYs and was the least costly. Over 15 months, total costs were $18 lower with a gain of 0.004 QALY in the genotype-guided strategy compared with empiric clopidogrel, and $899 lower with a gain of 0.0005 QALY compared with empiric prasugrel. The strongest predictor of the preferred strategy was the relative risk of thrombotic events in carriers compared with wild-type individuals treated with clopidogrel. Above a 47% increased risk, a genotype-guided strategy was the dominant strategy. Above a clopidogrel cost of $3.96 per day, genetic testing was no longer dominant but remained cost-effective. CONCLUSIONS: Among ACS patients undergoing PCI, a genotype-guided strategy yields similar outcomes to empiric approaches to treatment, but is marginally less costly and more effective.

Pharmacogenetics of clopidogrel: comparison between a standard and a rapid genetic testing.

AIMS: CYP2C19 variant alleles are independent 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 hundred acute coronary syndrome patients were genotyped for CYP2C19*2,*3,*4,*5, and *17 polymorphisms with two platforms: Verigene(®) and the TaqMan(®) system. RESULTS: Genotyping results obtained by the classical TaqMan approach and the rapid Verigene approach showed a 100% concordance for all the five 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 manual staff involvement and the relative cost resulted in higher cost for TaqMan than for Verigene. CONCLUSIONS: The Verigene system demonstrated good performance in terms of turnaround time and cost for the evaluation of the clopidogrel poor metabolizer status, giving genetic information in suitable time (206 min) for a therapeutic strategy decision.

Evaluating the risk-benefit profile of the direct-acting P2Y(12) inhibitor ticagrelor in acute coronary syndromes.

Ticagrelor is a direct-acting, oral, reversibly binding P2Y(12) receptor antagonist. As a cyclopentyltriazolopyrimidine, ticagrelor represents a new chemical class of agents that do not require metabolic activation and have consistent ability to inhibit platelet aggregation. The phase 3 PLATelet Inhibition and Patient Outcomes (PLATO) trial (NCT00391872) evaluated ticagrelor compared with clopidogrel in 18 624 patients with acute coronary syndromes (ACS), and demonstrated a significant reduction in the risk of death from vascular causes/myocardial infarction (MI)/stroke with ticagrelor (9.8% vs 11.7% with clopidogrel [hazard ratio, 0.84; 95% confidence interval, 0.77-0.92]; P < 0.001) without a significant increase in PLATO-defined major bleeding (11.6% vs 11.2%, respectively; P = 0.43). Myocardial infarction and death from vascular causes were separately significantly reduced, and death from any cause and stent thrombosis reductions achieved nominal statistical significance. Ticagrelor showed benefit over clopidogrel in almost all patient subgroups, including patients who had previously received clopidogrel, patients with both planned invasive or noninvasive treatment, patients with ST-segment elevation MI (STEMI) referred for primary percutaneous coronary intervention, patients with non-STEMI, and patients who underwent bypass surgery. Hence, the PLATO population reflected specifically those patients who would ordinarily receive thienopyridine-based antiplatelet therapy in a clinical setting. Although there are limitations in directly translating trial findings to clinical practice, the findings of PLATO suggest that for every 1000 ACS patients admitted to hospital, using ticagrelor instead of clopidogrel for 12 months would result in 14 fewer deaths or 11 fewer MIs. This review places the PLATO data in context, and assesses the role that ticagrelor may play in treating patients with ACS.