Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.6 (CAD)
 4,420 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Unstable angina (UA) and non-Q-wave myocardial infarction (NQWMI) are acute coronary syndromes with repeated, severe ischemic events of short duration. These events are mainly due to a rapid decrease in coronary blood flow, and to a rapid, reversible reduction of the arterial lumen in localized areas. Episodes often are a mixture of thrombus formation due to platelet aggregation and localized spasm, leading to vasoconstriction. Due to the short interval (minutes) of ischemic events, usually no or minimal irreversible myocardial damage takes place. The main goal of treatment is to prevent progression of this unstable situation into a myocardial infarction. In the majority of cases, this is possible with adequate treatment of vasodilatory substances like nitrates, long-acting dihydropyridines like amlodipine and betablockers. In addition heparin and particular antiaggregatory drugs inhibiting platelet activation by blocking the GPIIb/IIIa receptor, the common pathway for platelet aggregation, are applied to prevent thrombus formation. This, in the majority of cases allows a passivation of the acute situation, leaving time to undertake possible further steps as coronary angiography, eventually followed by PTCA of the culprit lesion or, in advanced cases of CAD, by CABG with complete revascularization.
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PMID:Unstable angina in 1998. 1069 86

Anticoagulants and antithrombotic drugs have played a key role in the prophylaxis, treatment and surgica/interventional management of thrombotic and cardiovascular disorders. There are several newer drugs which are currently developed for the anticoagulant management of cardiovascular diseases in both the medical and surgical indications. These include the low molecular weight heparins (LMWHs), antithrombin agents such as the Hirudin, Hirulog and Argatroban and indirect and direct anti-Xa drugs, represented by Pentasaccharide (Arixtra) and DX 9065a, respectively. Several other agents such as the natural and recombinant anti-Xa drugs and anti-tissue factor agents are also developed. The antiplatelet agents include Clopidogrel, Cilostazol, Anplag and GP IIb/IIIa inhibitors. For the subcutaneous indications, unfractionated heparin is gradually replaced by the low molecular weight heparins (LMWHs). LMWHs such as the Enoxaparin and Dalteparin are commonly used for the management of acute coronary syndrome. These drugs have been approved for the treatment of unstable angina and are currently undergoing rigorous trials for interventional indications. Arixtra is also developed for various subcutaneous indications. However, it exhibits lower anticoagulant effects and may not be optimal for intravenous and interventional purposes. At a higher dosage when administered intravenously the LMWHs produce varying degrees of anticoagulation at relatively lower activated clotting times (150-200). Several studies in vascular and cardiovascular interventions have shown that even at a relatively lower anticoagulant level the LMWHs are as effective as unfractionated heparin at the recommended dosages which produce a relatively higher level of anticoagulation (ACT > 200 secs.). Thus, these agents are currently developed for interventional and surgical indications. It should be emphasized that different LMWHs produce different degrees of anticoagulation and should therefore be individually optimized for a given interventional or surgical purposes. At a relatively high dosage the levels of LMWHs can be measured by using the ACT and APTT. When administered with such GP IIb/IIIa inhibitors as the Abciximab, Aggrastat or Eptifibratide, these drugs may require dosage adjustment However, since the introduction of the front loading of Clopidogrel, the unqualified use of GP IIb/IIIa is debated. LMWHs will find expanded indications in both the medical and surgical management of patients with cardiovascular disorders including atrial fibrillation and congestive heart failure. The only approved anti-Xa drug is represented by a synthetic heparinomimetic, namely, Arixtra. This drug is given for the prophylaxis of post orthopedic indications. This agent is undergoing additional clinical trials in the management of coronary artery diseases. Because of the dependence on antithrombin III (AT) and the sole anti-Xa effects, it has a narrow therapeutic index and its efficacy in this indication may be limited. Additional clinical trials are needed at this time to validate the clinical potential of this drug. The antithrombin agents (Hirudin, Hirulog and Argatroban) were initially developed for arterial indications. However, these agents are approved as a substitute anticoagulant in patients with heparin induced thrombocytopenia (HIT) and PCI. Currently an of these agents are being developed for surgical and interventional use. However, since there is no available antidote at this time, the development is somewhat limited. The antithrombin agents may be useful in patients with HIT which require further clinical validation. Many other anti-Xa agents are also developed. Most of these can be given parenterally. However, the clinical data is somewhat limited. Similarly, several of the new antiplatelet drugs can be administered parenterally and may be useful in CAD. Since most of these newer anticoagulant and antithrombotic drugs are mono-therapeutic their therapeutic index is rather limited. Only in combination these agents can mimic heparins. At this time it is safe to state that heparin and its LMW derivatives will remain the anticoagulant of choice for cardiovascular indications until these newer agents have been validated in extended clinical trials in polytherapeutic settings.
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PMID:Management of thrombotic and cardiovascular disorders in the new millenium. 1281 77

Patients with CKD and CAD have traditionally been a difficult population to diagnose and treat in the setting of ACS. In addition to having poorer outcomes post-ACS, data are lacking regarding best treatments available. Aggressive interventional and medical treatments in this group with already poor outcomes are not necessarily contraindicated and should always be considered. The appalling outcome for CKD patients post-ACS is improved by many therapies shown to benefit in the non-CKD patients. Data suggest that troponins are useful markers in CKD patients, that major bleeding is not increased with the use of GP IIb-IIIa antagonists, that thrombolytics have been used successfully in CKD patients, and that PCI electively and as a primary treatment for ACS is successful and probably more beneficial to treatment.
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PMID:Treatment of acute coronary syndromes in patients who have chronic kidney disease. 1575 68

We have investigated the frequencies of seven markers among 100 unrelated individuals with angiographically documented CAD (Coronary Artery Disease) and among 100 unrelated healthy blood donors in the central region of Corsica island (France). The seven polymorphisms analyzed were chosen from six candidate genes involved in (1) Renin-Angiotensin system: Angiotensin converting enzyme (ACE I/D), (2) Lipid metabolism: Cholesterol Ester Transfer Protein gene (CETP TAQ1B), (3) Platelet aggregation: alpha and beta subunits of the platelet GpIIb/GpIIIa integrin complex (GpIIb HPA3 and GpIIIa Pl(A1/A2)), (4) Coagulation fibrinolysis: Plasminogen Activator Tissue (PLAT TPA25 I/D) and Methylenetetrahydrofolate Reductase (MTHFR C677T and A1298C). The samples were genotyped using the polymerase chain reaction followed by restriction enzyme analysis for the RFLPs. No significant difference in allele frequencies between patient and control groups was observed. The occurrence of the MTHFR T677T genotype and of the T677T/A1298A compound genotype is higher in cases (20%) than in the controls (4%). Odds ratio seems to indicate that individuals with the MTHFR T677T genotype and the T677T/A1298A compound genotype had a 6-fold increased risk for developing CAD (ORs = 6; 95% CIs = 1.96-18.28) suggesting a possible association of MTHFR C677T with the risk of CAD in Corsican population.
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PMID:Prevalence of genetic risk factors for coronary artery disease in Corsica island (France). 1624 96

Individual variability in response to clopidogrel is known but its mechanism is poorly understood. We examined the relationship between glycoprotein IIIa polymorphism P1(A1/A2) and anti-thrombotic actions of clopidogrel. Clopidogrel (75 mg/d; 2 weeks) was administered to 48 normolipemic patients with coronary artery disease. Bleeding time, thrombin generation at the site of microvascular injury, platelet function under high shear, using PFA-100 with ADP cartridge, and platelet surface activation markers (P-selectin and fibrinogen binding sites on GPIIb/IIIa complex detected by PAC-1 antibody), were studied both before and after clopidogrel treatment. Both unstimulated and low-dose (0.02 microM and 1 microM) in vitro ADP-stimulated platelets were examined. GP IIIa polymorphism was assessed by polymerase chain reaction and restriction fragment length polymorphism analysis. We identified 32 P1(A1/A1) homozygotes, 15 P1(A1/A2 heterozygotes and one P1(A2/A2) homozygote. Clopidogrel significantly prolonged bleeding time in all subjects, but this effect was greater in P1(A2 carriers (p < 0.01). Furthermore, clopidogrel only depressed thrombin generation at the site of microvascular injury (p < 0.01) in P1(A2) patients and prolonged closure time measured in vitro by PFA-100 (p < 0.05). At baseline spontaneous expression of PAC-1 and P-selectin was higher in P1(A2) subjects as compared to P1(A1) homozygotes (p < 0.05 for both antigens). Clopidogrel lowered the expression of both markers affecting more P1(A2) carriers, so that the difference in binding PAC-1 antibody between platelets from P1(A1) and P1(A2) carriers disappeared, while the difference in P-selectin expression slightly diminished. Anti-thrombotic effects of clopidogrel are more pronounced in CAD patients carrying the P1(A2) allele than in P1(A1) homozygotes.
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PMID:Anti-thrombotic action of clopidogrel and P1(A1/A2) polymorphism of beta3 integrin in patients with coronary artery disease not being treated with aspirin. 1641 9

Non-ST-segment elevation myocardial infarction (NSTEMI) is defined as elevated cardiac biomarkers of necrosis in the absence of persistent ST-segment elevation in the setting of anginal symptoms or other acute event. It carries a poorer prognosis than most ST-segment elevation events, owing to the typical comorbidity burden of the older NSTEMI patients as well as diverse etiologies that add complexity to therapeutic decision-making. It may result from an acute atherothrombotic event ('Type 1') or as the result of other causes of mismatch of myocardial oxygen supply and demand ('Type 2'). Regardless of type and other clinical factors, the hospital medicine specialist is increasingly responsible for managing or coordinating the care of these patients. Following published guidelines for risk stratification and basing anti-anginal, anticoagulant, antiplatelet, other pharmacologic therapies, and overall management approach on that individualized patient risk assessment can be expected to result in better short- and long-term clinical outcomes, including near-term readmission and recurrent events. We present here a review of the evidence basis and expert commentary to assist the hospitalist in achieving those improved outcomes in NSTEMI. Given that the Society for Hospital Medicine cites care of patients with acute coronary syndrome as a core competency for hospitalists, it is essential that those specialists stay current on optimal NSTEMI care.Abbreviations: ACC: American college of cardiology; ACCOAST: comparison of prasugrel at the time of diagnosis in patients with non-ST elevation myocardial infarction; ACS: acute coronary syndrome; ADP: adenosine diphosphate; AHA: American heart association; ARB: angiotensin II receptor blocker; ASA: acetylsalicylic acid; CABG: coronary artery bypass graft: CAD: coronary artery disease; CCTA: coronary computed tomography angiography; cTn: cardiac troponin; CRUSADE: can rapid risk stratification of unstable angina patients suppress adverse outcomes with early implementation of the ACC/AHA guidelines; CURE: clopidogrel in unstable angina to prevent recurrent events; CURRENT: OASIS-7 clopidogrel and aspirin optimal dose usage to reduce recurrent events-seventh organization to assess strategies in ischemic syndromes; ECG: electrocardiogram; ED: emergency department; ESRD: endstage renal disease; ESC: European society of cardiology; FDA: food and drug administration; GRACE: global registry of acute coronary events; LVEF: left ventricular ejection fraction; MACE: major adverse cardiac event; MI: myocardial infarction; MVO2: myocardial oxygen demand; NSTEMI: non-ST-segment-elevation myocardial infarction; NTG: Nitroglycerin; PCI: percutaneous coronary intervention; plato: platelet inhibition and patient outcomes; PPI: proton pump inhibitor; PURSUIT: platelet glycoprotein IIb/IIIa in unstable angina: Receptor Suppression Using Integrilin Therapy; RAAS: Renin-Angiotensin-Aldosterone System; SHM: society of hospital medicine; STEMI: ST-segment-elevation myocardial infarction; TIMI: Thrombolysis in Myocardial Infarction; TRITON-TIMI:trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-thrombolysis in myocardial infarction.
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PMID:Contemporary NSTEMI management: the role of the hospitalist. 3181 70