These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.

CYP2C19 genotype-guided antiplatelet therapy following percutaneous coronary intervention is increasingly implemented in clinical practice. However, challenges such as selecting a testing platform, communicating test results, building clinical decision support processes, providing patient and provider education, and integrating methods to support the translation of emerging evidence to clinical practice are barriers to broad adoption. In this report, we compare and contrast implementation strategies of 12 early adopters, describing solutions to common problems and initial performance metrics for each program. Key differences between programs included the test result turnaround time and timing of therapy changes, which are both related to the CYP2C19 testing model and platform used. Sites reported the need for new informatics infrastructure, expert clinicians such as pharmacists to interpret results, physician champions, and ongoing education. Consensus lessons learned are presented to provide a path forward for those seeking to implement similar clinical pharmacogenomics programs within their institutions.

This paper summarizes the pharmacologic properties of vasoactive medications used in the treatment of shock, including the inotropes and vasopressors. The clinical application of these therapies is discussed and recent studies describing their use and associated outcomes are also reported. Comprehension of hemodynamic principles and adrenergic and non-adrenergic receptor mechanisms are salient to the appropriate therapeutic utility of vasoactive medications for shock. Vasoactive medications can be classified based on their direct effects on vascular tone (vasoconstriction or vasodilation) and on the heart (presence or absence of positive inotropic effects). This classification highlights key similarities and differences with respect to pharmacology and hemodynamic effects. Vasopressors include pure vasoconstrictors (phenylephrine and vasopressin) and inoconstrictors (dopamine, norepinephrine, and epinephrine). Each of these medications acts as vasopressors to increase mean arterial pressure by augmenting vascular tone. Inotropes include inodilators (dobutamine and milrinone) and the aforementioned inoconstrictors. These medications act as inotropes by enhancing cardiac output through enhanced contractility. The inodilators also reduce afterload from systemic vasodilation. The relative hemodynamic effect of each agent varies depending on the dose administered, but is particularly apparent with dopamine. Recent large-scale clinical trials have evaluated vasopressors and determined that norepinephrine may be preferred as a first-line therapy for a broad range of shock states, most notably septic shock. Consequently, careful selection of vasoactive medications based on desired pharmacologic effects that are matched to the patient's underlying pathophysiology of shock may optimize hemodynamics while reducing the potential for adverse effects.