Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.2.1.1 (ACS)
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Background In patients with non-ST elevation acute coronary syndrome (NST-ACS) that is treated invasively, glycoprotein (GP) IIb/IIIa inhibitors can be used either as upstream treatment in a coronary care unit or as downstream provisional treatment in selected patients who are undergoing percutaneous coronary intervention (PCI). The relative advantage of either strategy is unknown. The purpose of this study was to assess 30-day outcome of patients enrolled in a prospective NST-ACS registry and treated invasively with either of these two therapeutic strategies. Methods Patients treated invasively (coronary arteriography within 4 days of admission), in the prospective registry ROSAI-2, were divided into two groups according to the upstream use of GPIIb/IIIa inhibitors (n = 241), or not (n = 548). In the latter group, 76 (14%) patients received GPIIb/IIIa in association with a PCI procedure. Clinical and angiographic characteristics as well as in-hospital and 30-day outcome of these two groups of patients were compared. Results The two groups were similar with respect to age, sex, presence of hypertension, diabetes, number of PCI procedures. However, patients treated with upstream GPllb/llla blockers had more frequently ST-segment depression (P = 0.002), a high TIMI risk score (P = 0.01) and were more frequently admitted to centres with Cath Lab facilities (P = 0.001). At 30-day follow-up, the composite of death, acute myocardial infarction and stroke, as well as major bleeding, was not significantly different between the two groups, although it occurred more frequently in patients who received upstream GPIIb/IIIa blockers (9.5% versus 5.7% and 1.7% versus 0.2%, respectively). By multivariate analysis, diabetes [odds ratio (OR) = 2.22, 95% confidence interval (CI) = 1.2-4.09] and a diagnosis on admission of non-Q-wave myocardial infarction (OR = 2.0, 95% Cl = 1.10-3.6) were independently related to outcome. No additional risk or benefit was related to upstream GPIIb/IIIa inhibitor treatment (OR = 1.5, 95% Cl = 0.84-2.68). Conclusions Among invasively-treated patients with NST-ACS, upstream treatment with GPIIb/IIIa inhibitors was used in those with a higher clinical risk profile, whereas downstream treatment was reserved for a limited number of patients undergoing PCI. Thirty-day outcome was similar in the two groups, irrespective of the treatment strategy used.
J Cardiovasc Med (Hagerstown) 2006 Mar
PMID:Use of glycoprotein IIb/IIIa inhibitors in invasively-treated patients with non-ST elevation acute coronary syndrome. 1664 80

We analyzed 14 cases of new lesions inside implanted bare-metal stents. In every case, there was no angiographic restenosis within 3 years, but a new lesion was observed inside a stented segment at long-term follow-up (>5 years). Fourteen cases were evaluated: 9 with Wiktor stents, 2 with Palmaz-Schatz stents, and 3 with ACS Multilink stents. The interval from stent implantation to follow-up angiography was 63-147 months (89 +/- 23). Thirteen lesions were treated by percutaneous coronary intervention (PCI) and stenotic tissue was obtained by directional coronary atherectomy (DCA) in 10 cases. All retrieved samples were composed of newly developed atherosclerosis facing the healed neointimal layer, and four samples showed histopathological findings of acute coronary syndrome. Stent struts were retrieved in four cases and no inflammation was observed surrounding them. Qualitative and quantitative analysis of stent struts was performed in two cases that showed no metal corrosion. These findings suggest that new atherosclerotic progression occurred inside the implanted stent without peristrut inflammation.
Catheter Cardiovasc Interv 2006 Oct
PMID:Histopathological findings of new in-stent lesions developed beyond five years. 1804 89

Thrombosis superimposed on arteriosclerosis is the principal cause of mortality and morbidity in patients with arteriosclerosis. The use of antiplatelet agents and anticoagulants in the treatment of arteriosclerosis is well established, based on many large randomized trials. Aspirin is indicated for primary prevention in patients at increased risk of developing symptomatic atherosclerotic vascular disease. For patients with known vascular disease, antiplatelet therapy with aspirin is a well-established treatment. For high-risk patients such as those with acute coronary syndromes (ACS; unstable angina, myocardial infarction), dual antiplatelet therapy with aspirin and clopidogrel is indicated, based on results of the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial. Platelet glycoprotein IIb/IIIa agents are powerful inhibitors of platelet function and are also effective in ACS, but the benefit is confined to high-risk patients. Anticoagulation with heparin or low-molecular-weight heparin (eg, enoxaparin) is also effective, with an approximately 50% reduction in cardiovascular events. These agents are also indicated for patients undergoing percutaneous coronary intervention. Prolonged dual antiplatelet therapy (at least 6 months) is recommended for patients receiving drug-eluting stents. The efficacy of antiplatelet therapy is thus well established in treating atherothrombosis, but aggressive therapy is associated with an increased bleeding risk. Newer agents may provide improved efficacy with a lower risk of bleeding.
Rev Cardiovasc Med 2005
PMID:Use of antiplatelet agents and anticoagulants for cardiovascular disease: current standards and best practices. 1771 74

The Clinical Trials described in this article were presented at the Hotline and Clinical Trial Update Sessions of the European Society of Cardiology Congress held in September 2007 in Vienna, Austria. The sessions chosen for this article represent the scope of interest of Cardiovascular Drugs and Therapy. The presentations should be considered preliminary, as further analyses could alter the final publication of the results of these studies. PROSPECT evaluated echocardiographic criteria for optimal selection of patients with moderate to severe heart failure who may benefit from cardiac resynchronisation therapy, however concluded that no single echocardiographic measure can be recommended. EVEREST found that tolvaptan, a vasopressin V(2) antagonist, resulted in early weight reduction and improvement of dyspnoea in patients with acute heart failure, but lacked long term improvement. In ARISE, the anti-oxidant succinobucal did not affect the primary outcome in high risk cardiovascular patients, but improved the combination of cardiovascular death, myocardial infarction and stroke, and diabetic control in diabetics. ALOFT showed that the addition of the renin inhibitor aliskiren to an ACE inhibitor or ARB and a beta-blocker leads to favourable effects on neurohormonal actions in heart failure. FINESSE markedly improved coronary patency before PCI with half-dose reteplase/abciximab in STEMI patients, however without significantly improving short-term outcome. The Prague-8 Study evaluated whether routine clopidogrel administered >6 h pre-angiography would be a safe way to achieve therapeutic drug levels in case a follow-up intervention would be considered immediately, but appeared not justified because of bleeding complications. CARESS in MI showed that high risk patients with evolving STEMI who undergo thrombolytic therapy should undergo PCI early after the thrombolysis. Finally, the ACUITY trial found that in moderate or high risk Non ST elevation ACS patients triaged to PCI, coronary artery bypass graft (CABG) surgery, or medical management, bivalirudin, with or without associated GPIIb/IIIa inhibitor therapy, resulted in a marked reduction of bleeding at 30 days whilst preserving the ischemic and mortality benefit at 1 year follow up.
Cardiovasc Drugs Ther 2007 Dec
PMID:Clinical trials update from the European Society of Cardiology Congress in Vienna, 2007: PROSPECT, EVEREST, ARISE, ALOFT, FINESSE, Prague-8, CARESS in MI and ACUITY. 1799 67

Glycoprotein (GP) IIb/IIIa receptor antagonists inhibit the binding of ligands to activated platelet GP IIb/IIIa receptors and, therefore, prevent the formation of platelet thrombi. Additional antithrombin therapy should be given in connection with GP IIb/IIIa administration. Eptifibatide is a small heptapeptide, which is highly selective and rapidly dissociates from its receptor after cessation of therapy. In clinical trials (IMPACT-II and ESPRIT) concomitant administration of eptifibatide to patients undergoing percutaneous coronary intervention (PCI) reduced thrombotic complications. In the PURSUIT trial, in patients with non-ST-elevation acute coronary syndromes, eptifibatide, compared to placebo, significantly reduced the primary endpoint of death and nonfatal myocardial infarction at 30 days. In patients with STEMI eptifibatide has been studied as an adjunct to fibrinolysis and primary PCI; it improved epicardial flow and tissue reperfusion. Current studies are evaluating eptifibatide as upstream therapy in high-risk patients with NSTE-ACS, in the EARLY-ACS and in comparison with abciximab in patients with primary PCI in the EVA-AMI trial.
Cardiovasc Drug Rev 2007
PMID:A review of clinical trials with eptifibatide in cardiology. 1807 31

The purpose of this study was to compare cardiac markers in the pericardial fluid and serum in order to evaluate preoperative myocardial injury. Thirty patients were divided into three groups. The first group (AVR; n=10) received an aortic valve replacement. The second group (SA; n=10) included patients with stable angina who underwent elective coronary artery bypass grafting (CABG). The third group (ACS; n=10) included patients with acute coronary syndrome who underwent urgent CABG. Pericardial fluid and venous samples were taken after opening the pericardium and 24 h postoperatively. Serum and pericardial concentration of troponin I (cTnI), creatine kinase (CK), its MB isoenzyme (CK-MB) and myoglobin were determined. Preoperative pericardial cTnI was significantly (P<0.01) higher than in serum in all groups. Preoperative pericardial CK, CK-MB and myoglobin were significantly (P<0.01) lower than in serum in groups AVR and SA. Preoperative pericardial and serum cTnI were significantly higher in the ACS than in AVR and SA groups (P<0.01). Postoperative pericardial concentration of all markers was significantly higher (P<0.01) than in serum in all groups. We conclude that preoperative pericardial accumulation of cTnI may reflect subclinical injury which may not be demonstrated by the usual laboratory tests.
Interact Cardiovasc Thorac Surg 2008 May
PMID:Biochemical markers of myocardial injury in the pericardial fluid of patients undergoing heart surgery. 1825 49

Fondaparinux sodium (Arixtra) is a synthetic, sulfated pentasaccharide, selective factor Xa inhibitor that is indicated in Europe for preventing thrombus formation in patients with acute coronary syndromes (ACS; the focus of this review), including those with ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), or unstable angina.The large (n = 20,078), well designed OASIS-5 trial showed that subcutaneous fondaparinux 2.5 mg/day for <or=8 days was noninferior to subcutaneous enoxaparin 1 mg/kg twice daily (once daily in those with renal dysfunction) in reducing death or ischemic events at 9 days and the efficacy was maintained for up to 6 months (study end) in patients with unstable angina or NSTEMI. During this time, major bleeding occurred in fewer fondaparinux than enoxaparin recipients, resulting in a benefit: risk balance favoring fondaparinux. The incidence of death or reinfarction at 30 days was significantly lower in recipients of subcutaneous fondaparinux 2.5 mg/day than in those who received usual care (including unfractionated heparin [UFH] treatment as indicated) in patients with STEMI in the large (n > 12,000) OASIS-6 trial. There were no differences in the incidence of major bleeding between these groups, resulting in a benefit : risk balance favoring fondaparinux. The specificity and selectivity of fondaparinux, combined with its long half-life and 100% bioavailability, allows once-daily anticoagulation without the need for monitoring activated clotting time. Subcutaneous fondaparinux was noninferior to enoxaparin treatment in patients with unstable angina or NSTEMI, and was more effective than usual care in those with STEMI. Fondaparinux has a favorable tolerability profile, particularly with regard to the risk of major bleeding, and limited data suggest that it is more cost effective than enoxaparin in the short term. Thus, overall, clinical evidence suggests that fondaparinux has a valuable place in the treatment of patients with ACS.
Am J Cardiovasc Drugs 2008
PMID:Fondaparinux sodium: a review of its use in the management of acute coronary syndromes. 1842 94

Statins exert a number of beneficial effects on endothelial function and atherosclerotic plaque, modulating oxidative stress and inflammation, with subsequent, well documented, primary and secondary prevention of coronary artery disease. Periprocedural myocardial infarction and contrast induced nephropathy, after percutaneous coronary intervention (PCI), are associated with a worse outcome on long term follow-up. In the ARMYDA study, pretreatment with statins before elective PCI reduces periprocedural myocardial infarction in patients with stable angina. Moreover, the ARMYDA ACS was the first randomized, prospective trial that demonstrated that an acute loading with a high dose of atorvastatin prevents myocardial damage in patients with unstable syndromes undergoing early (<48 hours) coronary angiography and consequent angioplasty. Statins could also have beneficial effects by reducing expression of adhesion molecules in endothelial cells (ICAM-1 and E-Selectin) as demonstrated in the ARMYDA-CAMS study. Furthermore, patients receiving statins at the time of procedure show a significantly reduced incidence of contrast-induced nephropathy. All this evidence may strongly influence the clinical practice of an interventional cardiologist.
Ther Adv Cardiovasc Dis 2008 Apr
PMID:Percutaneous coronary interventions and statins therapy. 1912 13

Whole gene expression analysis through microarray technologies revolutionized the manner of identifying changes in biological events and complex diseases, such as cardiovascular settings. These new methodologies may scan up to 35 000 transcripts at once rather than screening a small amount of genes one at a time. The ability of microarrays to provide a broad insight into the disease process directly within the tissues provides a unique insight into the intracellular perturbations of the cell organization and function and sheds an entirely unique new perspective on the heart failure process. Commonalities and differences at the molecular level will identify critical pathways of pathogenesis, and response to therapy, or both: indeed, gene expression profiling holds tremendous promise for classifying clinical phenotypes, developing prognostic predictors and, most importantly, providing novel unbiased insights into the mechanisms underlying heart disease and, eventually, novel causative genes. On the contrary, established proteomic technologies, together with the new alternative strategies currently under evaluation (i.e. metabolomics), are now making possible the translation of data obtained on the bench to the daily clinical routine with the discovery of new diagnostic/prognostic biomarkers (such as troponin for ACS and BNP for congestive heart failure) and the identification of new therapeutic approaches for combating heart diseases. Finally, genomic studies (including transcriptomics) together with proteomics should not represent a challenge for who is going to win the final battle, but rather they should provide a setting in which together and in a complementary fashion the final fight against heart disease can be won.
J Cardiovasc Med (Hagerstown) 2009 May
PMID:Transcriptomic and proteomic analysis in the cardiovascular setting: unravelling the disease? 1944 58

The ability to mechanically dilate and treat stenoses in the coronary arteries opened a new chapter in cardiovascular medicine. Percutaneous coronary intervention (PCI) has been shown to improve outcomes among patients with acute coronary syndromes as well as improve symptoms among patients with stable coronary artery disease. Adjunctive antiplatelet therapy plays a critical role both in the periprocedural setting as well as in the long-term management of atherothrombosis. Over the past several years, clinical trials of novel compounds and treatment strategies have further refined our pharmacotherapeutic approach. Aspirin remains the cornerstone for antiplatelet therapy across the spectrum of ischemic heart disease. In contrast, studies of glycoprotein IIb/IIIa inhibitors suggest a more limited role, particularly when used in addition to contemporary dual antiplatelet therapy. Clopidogrel, the most widely used P2Y(12) adenosine diphosphate receptor blocker--although having demonstrated efficacy in patients with ST-segment elevation myocardial infarction, non-ST-segment elevation acute coronary syndrome, and stable coronary artery disease undergoing PCI--has several limitations, including delay in onset, variability in response, and modest potency. The third-generation thienopyridine, prasugrel, as well as nonthienopyridine inhibitors of the P2Y(12) receptor such as ticagrelor and cangrelor address these shortcomings, offering more potent, consistent, and rapid platelet inhibition. Prasugrel and ticagrelor led to significant reductions in adverse cardiovascular events, including cardiovascular mortality for the latter, whereas cangrelor met noninferiority compared with 600 mg of clopidogrel in patients with ACS undergoing PCI. There are myriad novel compounds at varying stages of development, including thrombin receptor antagonists whose role in the periprocedural and long-term setting will be defined through further study. Significant questions regarding antiplatelet therapy remain unanswered, including the role of genetic and platelet function testing to "tailor therapy"; the optimal duration of therapy; and the optimal mechanism to deliver high-quality, cost-effective antiplatelet therapy to all patients.
JACC Cardiovasc Interv 2010 Jun
PMID:The state of periprocedural antiplatelet therapy after recent trials. 2063 Apr 50


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