trials 2,3 and a meta-analysis 4 have shown that treatment with clopidogrel in CYP2C19 LOF carriers results in an increase in ischemic events after PCI compared with those treated with drugs that are less susceptible to CYP2C19, including prasugrel or ticagrelor. In this context, the US Food and Drug Administration has suggested an alternative P2Y12-I to clopidogrel for patients who are CYP2C19 poor metabolizers. 5 Recently, some populations receiving PCI have comprised patients with high bleeding risk (HBR). The Academic A P2Y12 inhibitor (P2Y12-I) in addition to aspirin is the cornerstone of treatment to reduce subsequent ischemic events in patients undergoing percutaneous coronary intervention (PCI). Clopidogrel, a conventional P2Y12-I, is a prodrug that undergoes metabolic transformation in the liver by cytochrome P450 (CYP) 2C19 to elicit its antiplatelet effect. A CYP2C19 loss-offunction (LOF) allele leads to a lower plasma concentration of the active clopidogrel metabolite, resulting in reduced inhibition of platelet aggregation. 1 Randomized control
Long QT syndrome (LQTS) is an inherited arrhythmic disease with prolongation of QT interval on the electrocardiogram and fatal cardiac arrhythmia, called torsade de pointes (TdP) [1,2]. The typical LQTS is a congenital form with TdP of the onset induced by autonomic activity, e.g. exercise in LQTS type 1 (LQT1) or emotion and unexpected noise in LQTS type 2 (LQT2) [3]. To date, a variety of mutations were reported in 15 candidate genes responsible for congenital LQTS [2]. On the other hand, another form of LQTS, acquired LQTS, is caused by secondary factors, e.g. hypokalemia [4], drugs [5,6], or bradycardia [7]. Although acquired LQTS presents no or mild phenotypes with normal to borderline QT prolongation in the absence of secondary factors, this form may carry a mutation underlying the LQTS-related candidate genes (silent mutation carriers) [5,8-13].
Aluminum transfer and dialysance during haemodialysis and plasma aluminum concentrations in haemodialysis patients were examined. Plasma aluminum in 30 volunteer outpatients tended to decrease after 5-hour dialysis (6.35 +/- 3.02 micrograms/dl before haemodialysis; 5.41 +/- 2.60 micrograms/dl after haemodialysis). The decrease was mainly due to diffusion despite haemoconcentration evidenced by a significant increase in the haematocrit and total plasma protein during dialysis. To study the changes resulting from diffusion, we measured aluminum in the arterial blood and in the dialysate at the inflow and outflow sites of the dialyzer. There was a non-significant decrease in the plasma aluminum of arterial blood from 6.20 +/- 2.90 to 5.64 +/- 2.55 micrograms/dl, but a significant increase in the dialysate aluminum from 0.38 +/- 0.18 micrograms/dl to 1.10 +/- 0.66 micrograms/dl. Aluminum diffused across the dialyzer from the blood to the dialysate in 23 cases and into the blood in 7 others. When aluminum dialysance is high, plasma aluminum can be removed to the dialysate during haemodialysis.
Clinical characteristics were not specific for mutation locations but specific for respective mutations in our LQT1 patients. Patients should be evaluated by their own mutations to prevent severe cardiac events.
Background:The association between cytochrome P450 (CYP) 2C19 genotypes and adverse events in patients treated with clopidogrel or prasugrel after percutaneous coronary intervention (PCI) in the Japanese population is unclear.
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