dihydropyridines and Coronary-Stenosis

To develop a new procedure to evaluate the functional consistence of the radial artery (RA) as a conduit used in aortocoronary bypass surgery (ACBS), to verify the prognostic value of the changed diameter of RA, and to prevent its spasm.. The study enrolled 34 patients aged 59.4 +/- 8.6 years with coronary artery stenoses, who underwent ACBS using a RA conduit. While preparing them for surgery, endothelium-dependent vasodilation (EDVD) of RA, i.e. the magnitude of a change in its diameter (deltaD) was assessed; RA tone and nitric oxide (NO) concentrations were estimated during surgery; RA EDVD was re-estimated in 12 lercanidipine-treated patients with deltaD < 8%.. The patients were primarily divided into 2 groups: 1) deltaD > or = 8% (RA spasm intra- and postoperatively); 2) EDVD deltaD < 8% (RA spasm). Significant differences between Groups 1 and 2 were intraoperatively recorded in vascular wall tone (U = 1.0; Z = -2.3; p = 0.02) and NO concentrations (p = 0.0); a relationship was found between these parameters. After lercanidipine treatment, the degree of deltaD = 4.36 +/- 1.89% increased to 11.32 +/- 2.22% (p = 0.0) and RA tone dropped from -1.68 to -3.9 mm in Group 2a with the baseline decreased vasodilating activity of RA.. Ultrasound assessment of the vasodilating activity of RA provides adequate evidence about its arterial wall tone during surgery. deltaD < 8% is prognostically unfavorable and serves as a contraindication to the use of RA as a conduit during ACBS. The administration of lercanidipine allows effective correction of the dilatory capacities of an arterial conduit.

Topics: Aged; Calcium Channel Blockers; Coronary Artery Bypass; Coronary Stenosis; Dihydropyridines; Female; Graft Occlusion, Vascular; Humans; Male; Middle Aged; Monitoring, Intraoperative; Nitric Oxide; Predictive Value of Tests; Preoperative Care; Radial Artery; Ultrasonography; Vasodilation

Because of the known CYP3A4 inhibition by calcium-channel blockers (CCBs), we hypothesized that there might be a drug-drug interaction between clopidogrel and dihydropyridines in patients with coronary artery disease.. Clopidogrel is activated by CYP3A4, which also metabolizes CCBs of the dihydropyridine class.. Responsiveness to clopidogrel was assessed by the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay and aggregometry in 200 patients with coronary artery disease undergoing percutaneous coronary intervention.. The platelet reactivity index (PRI) (in the VASP assay, normal range 69% to 100%) was higher in patients receiving both clopidogrel and CCBs (61%) as compared with patients receiving clopidogrel without CCBs (48%). The absolute difference was 13% (95% confidence interval: 6% to 20%; p = 0.001), and the relative difference approached 21%. A decreased platelet inhibition by clopidogrel (PRI >69%) was seen in 40% of patients with concomitant CCB treatment and in 20% of patients without concomitant treatment (chi-square test, p = 0.008). Intake of CCB remained an independent predictor of reduced platelet inhibition by clopidogrel after adjustment for cardiovascular risk factors. Adenosine diphosphate-induced platelet aggregation was 30% higher in patients on concomitant CCB treatment compared with patients without CCBs (p = 0.046). Moreover, intake of CCBs was associated with adverse clinical outcome. In vitro incubation with CCBs (nimodipine, verapamil, amlodipine, and diltiazem) did not alter the PRI or the adenosine diphosphate-induced platelet aggregation of patients taking clopidogrel. This finding indicates that the negative effect occurs in vivo, conceivably at the level of the CYP3A4 cytochrome.. Coadministration of CCBs is associated with decreased platelet inhibition by clopidogrel.

Topics: Aged; Angioplasty, Balloon, Coronary; Calcium Channel Blockers; Case-Control Studies; Cell Adhesion Molecules; Clopidogrel; Coronary Restenosis; Coronary Stenosis; Dihydropyridines; Drug Interactions; Female; Flow Cytometry; Humans; Logistic Models; Male; Microfilament Proteins; Middle Aged; Phosphoproteins; Phosphorylation; Platelet Aggregation; Platelet Aggregation Inhibitors; Prospective Studies; Reference Values; Risk Assessment; Sensitivity and Specificity; Statistics, Nonparametric; Ticlopidine; Treatment Outcome

It has been reported that the morbidity rate of vasospastic angina is higher in Japan compared to western countries, and its prognosis has already been reported. However, the prognosis of vasospastic angina in relation to coronary angiographic findings, prognostic risk factors and treatment has not yet been fully investigated.. From January 2000 to October 2005, 1047 patients with vasospastic angina diagnosed by coronary angiography at Gifu University Hospital and related hospitals were registered in a cohort study (follow-up rate: 91.4%, median follow-up duration: 3.8 years). The presence of coronary artery stenosis, diabetes mellitus, total spasm, and age of more than 65 years had a negative prognostic impact on cardiovascular events. Patients were treated with calcium channel blockers such as diltiazem (CAS 33286-22-5, CAS 42399-41-7), amlodipine (CAS 111470-99-6), nifedipine (CAS 21829-25-4), and benidipine (CAS 91599-74-5). Among these calcium channel blockers, when patient background was matched by the propensity score in patients treated with calcium channel blockers only, the cardiovascular event rate was significantly lower in the benidipine group than in the diltiazem group.. The study demonstrated for the first time that total spasm is a risk factor, independent of other factors, for cardiovascular events in patients with vasospastic angina. Treatment with benidipine showed a better prognosis than that with diltiazem.

Topics: Adult; Aged; Aging; Amlodipine; Angina Pectoris; Calcium Channel Blockers; Cohort Studies; Coronary Angiography; Coronary Stenosis; Coronary Vasospasm; Diabetes Complications; Dihydropyridines; Diltiazem; Ergonovine; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nifedipine; Oxytocics; Prognosis; Risk Factors