Background CYP2C19 loss-of-function (LOF) alleles impair clopidogrel effectiveness after percutaneous coronary intervention (PCI). The feasibility, sustainability and clinical impact of using CYP2C19 genotype-guided dual antiplatelet therapy (DAPT) selection in practice remains unclear. Methods and Results A single-center observational study was conducted in 1193 patients who underwent PCI and received DAPT following implementation of an algorithm that recommends CYP2C19 testing in high-risk patients and alternative DAPT (prasugrel or ticagrelor) in LOF allele carriers. The frequency of genotype testing and alternative DAPT selection were the primary implementation endpoints. Risk of major adverse cardiovascular or cerebrovascular (MACCE) and clinically significant bleeding events over 12 months were compared across genotype and DAPT groups by proportional hazards regression. CYP2C19 genotype was obtained in 868 (72.8%) patients. Alternative DAPT was prescribed in 186 (70.7%) LOF allele carriers. CYP2C19 testing (P<0.001) and alternative DAPT use in LOF allele carriers (P=0.001) varied over time. Risk for MACCE was significantly higher in LOF carriers prescribed clopidogrel versus alternative DAPT (adjusted hazard ratio [HR] 4.65, 95% confidence interval [CI] 2.22–10.0, P<0.001), whereas no significant difference was observed in those without a LOF allele (adjusted HR 1.37, 95% CI 0.72–2.85, P=0.347). Bleeding event rates were similar across groups (log-rank P=0.816). Conclusions Implementing CYP2C19 genotype-guided DAPT is feasible and sustainable in a real-world setting, but challenging to maintain at a consistently high level of fidelity. The higher risk of MACCE associated with clopidogrel use in CYP2C19 LOF allele carriers suggests that use of genotype-guided DAPT in practice may improve clinical outcomes.

Purpose-To evaluate the frequency and clinical impact of switches in antiplatelet therapy following implementation of CYP2C19 genotyping after percutaneous coronary intervention (PCI). Methods-The frequency of escalation (clopidogrel switched to prasugrel/ticagrelor) and deescalation (prasugrel/ticagrelor switched to clopidogrel) was evaluated in 1063 PCI patients who underwent CYP2C19 genotyping. Risk of major adverse cardiovascular or cerebrovascular (MACCE) and bleeding events over one-year was evaluated. Results-Antiplatelet therapy switches were common (19%), with escalation (101/115: 88%) and de-escalation (77/84: 92%) occurring predominantly in patients with and without a CYP2C19 nonfunctional allele, respectively. Nonfunctional allele carriers initiated and continued on clopidogrel had a significantly higher risk of experiencing either a MACCE or bleeding event Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Cyclooxygenase (COX)-derived prostanoids contribute to angiotensin II (ANG II) hypertension (HTN). However, the specific mechanisms by which prostanoids act are unclear. ANG II-induced HTN is caused partly by increased sympathetic nervous system activity, especially in a setting of high dietary salt intake. This study tested the hypothesis that COX-derived prostanoids cause ANG II-salt sympathoexcitation and HTN. Experiments were conducted in conscious rats. Infusion of ANG II (150 ng·kg(-1)·min(-1) sc) caused a marked HTN in rats on 2% salt diet, but a much smaller increase in blood pressure in rats on 0.4% salt diet. The nonselective COX inhibitor ketoprofen (2 mg/kg sc) given throughout the ANG-II infusion period attenuated HTN development in rats on 2% NaCl diet, but not in rats on 0.4% NaCl diet. The acute depressor response to ganglion blockade was used to assess neurogenic pressor activity in rats on 2% NaCl diet. Ketoprofen-treated rats showed a smaller fall in arterial pressure in response to ganglion blockade during ANG-II infusion than did nontreated controls. In additional experiments, ketoprofen-treated rats exhibited smaller increases in plasma norepinephrine levels and whole body norepinephrine spillover than we previously reported in ANG II-salt HTN. Finally, the effects of the selective COX-1 inhibitor SC560 (10 mg·kg(-1)·day(-1) ip) and the selective COX-2 inhibitor nimesulide (10 mg·kg(-1)·day(-1) ip) were investigated. Treatment with SC560 but not nimesulide significantly reduced blood pressure and the depressor response to ganglion blockade in ANG II-salt HTN rats. The results suggest that COX-1 products are critical for sympathoexcitation and the full development of ANG II-salt HTN in rats.

New oral anticoagulants (NOAC) serve as alternatives for patients currently using warfarin for the prevention and treatment of venous thromboembolic (VTE) disease. This article provides a brief summary of the clinical use of these drugs as well as a review of the landmark clinical trials which evaluated described their safety and efficacy. As more data becomes available, a fundamental understanding of these medications will be vital to cardiovascular practitioners managing patients with VTE.

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