Application of Current Guidelines to the Management of Unstable Angina and Non-ST-Elevation Myocardial Infarction

Braunwald, Eugene

doi:10.1161/01.cir.0000086952.14979.32

Cited by 57 publications

(39 citation statements)

References 93 publications

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“…6,8 Two large studies in patients with acute coronary syndromes have shown that pretreatment with clopidogrel (given a mean of 6 days before intervention in the observational PCI-CURE [Percutaneous Coronary Intervention-Clopidogrel in Unstable angina to prevent Recurrent Events] and 3 to 24 hours in the randomized CREDO [Clopidogrel for the Reduction of Events During Observation] trial) 5,9 may have beneficial effects, possibly by decreasing periprocedural ischemia and distal embolization, protecting the microvascular bed, and counterbalancing the postprocedural "procoagulant status." Accordingly, current common clinical practice is pretreatment with a 300-mg loading dose of clopidogrel 16 at least 6 hours before the procedure in patients with acute coronary syndromes, 10 as well as in those undergoing elective intervention. 1 The use of a 300-mg loading dose of clopidogrel derives from dosefinding data on healthy volunteers 17 ; however, patients with coronary artery disease may have enhanced platelet reactivity as compared with healthy individuals, 18 possibly requiring more aggressive platelet inhibition.…”

Section: Discussionmentioning

confidence: 99%

Randomized Trial of High Loading Dose of Clopidogrel for Reduction of Periprocedural Myocardial Infarction in Patients Undergoing Coronary Intervention

et al. 2005

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Background-Aggressive platelet inhibition is crucial to reduce myocardial injury and early cardiac events after coronary intervention. Although observational data have suggested that pretreatment with a high loading dose of clopidogrel may be more effective than a conventional dose, this hypothesis has never been tested in a randomized trial. Methods and Results-A total of 255 patients scheduled to undergo percutaneous coronary intervention were randomized to a 600-mg (nϭ126) or 300-mg (nϭ129) loading regimen of clopidogrel given 4 to 8 hours before the procedure.Creatine kinase MB, troponin I, and myoglobin levels were measured at baseline and at 8 and 24 hours after intervention. The primary end point was the 30-day occurrence of death, myocardial infarction (MI), or target vessel revascularization. The primary end point occurred in 4% of patients in the high loading dose versus 12% of those in the conventional loading dose group (Pϭ0.041) and was due entirely to periprocedural MI. Peak values of all markers were significantly lower in patients treated with the 600-mg regimen (PՅ0.038). Safety end points were similar in the 2 arms. At multivariable analysis, the high loading regimen was associated with a 50% risk reduction of MI (OR 0.48, 95% CI 0.15 to 0.97, Pϭ0.044). An incremental benefit was observed in patients randomized to the 600-mg dose who were receiving statins, with an 80% risk reduction. Conclusions-Pretreatment with a 600-mg loading dose of clopidogrel 4 to 8 hours before the procedure is safe and, as compared with the conventional 300-mg dose, significantly reduced periprocedural MI in patients undergoing percutaneous coronary intervention. These results may influence practice patterns with regard to antiplatelet therapy before percutaneous revascularization.

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Section: Discussionmentioning

confidence: 99%

Randomized Trial of High Loading Dose of Clopidogrel for Reduction of Periprocedural Myocardial Infarction in Patients Undergoing Coronary Intervention

et al. 2005

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“…11 Thus, thrombin inhibition is important in the treatment of acute coronary syndromes and during percutaneous coronary intervention. 12,13 Argatroban is an arginine-derived, small molecule, thrombin inhibitor that binds selectively to the catalytic site of thrombin. 14 Enoxaparin is a low-molecular-weight heparin that inhibits thrombin via both anti-FXa (80%) and anti-FIIa activity (20%).…”

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confidence: 99%

Platelet Activity, Coagulation, and Fibrinolysis During Exercise in Healthy Males

Blombäck

et al. 2007

ATVB

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Background-Relationships between exercise-induced activation of platelets, blood coagulation, and fibrinolysis, and the importance of thrombin for responses to exercise are not clear. Methods and Results-Effects of thrombin inhibition on hemostatic parameters were examined in a double-blind crossover study comparing the direct thrombin inhibitor argatroban (350 g/kg intravenous bolus followed by 25 g/kg per minute of infusion), the indirect thrombin inhibitor enoxaparin (0.75 mg/kg, intravenous bolus), or placebo (saline) in 21 healthy males. Measurements were made at rest, before and during/after thrombin inhibitor treatment, and immediately after exhaustive exercise. At rest argatroban abolished, and enoxaparin attenuated platelet activation by thrombin, but not by adenosine diphosphate. Argatroban and, even more so, enoxaparin decreased thrombin generation (prothrombin F1ϩ2) and the coagulation potential, and increased the fibrinolytic potential. Exercise increased circulating activated platelets (from 5.5Ϯ0.3 to 9.4Ϯ0.9ϫ10 9 /L; PϽ0.001), circulating platelet-platelet microaggregates, the platelet responsiveness to in vitro stimulation, leukocyte activation (leukocyte CD11b expression and plasma elastase), and platelet-leukocyte aggregation (PϽ0.01 for all). Exercise increased coagulation (F1ϩ2; PϽ0.01) and fibrinolysis, but did not alter the balance between them; fibrin gel permeability increased (PϽ0.01), probably because of release of endogenous tissue plasminogen activator from the vessel wall. Neither argatroban nor enoxaparin counteracted exercise-induced platelet or leukocyte activation. Both thrombin inhibitors augmented exercise effects on fibrinolysis. Conclusions-Strenuous exercise enhances platelet and leukocyte activation independently of thrombin. Exercise augments both coagulation and fibrinolysis, but the balance between them appears to be maintained. At therapeutic dosages argatroban counteracted thrombin-induced platelet activation most efficiently, whereas enoxaparin had somewhat stronger anticoagulant and profibrinolytic effects.

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“…3-7 Evidence suggests that invasive management strategies primarily benefit elderly or high-risk patients and may not be warranted in lower-risk patients. [8][9][10][11] However, in practice these interventions have been primarily directed to younger, lower-risk patients. 12 Noninvasive, inexpensive, medical management, including aspirin, angiotensin-converting enzyme inhibitors, and β-blockers, as well as thrombolysis, reduces mortality following AMI.…”

mentioning

confidence: 99%

Long-term Outcomes of Regional Variations in Intensity of Invasive vs. Medical Management of Medicare Patients With Acute Myocardial Infarction

Stukel¹,

Lucas²,

Wennberg³

2005

ACC Current Journal Review

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Application of Current Guidelines to the Management of Unstable Angina and Non-ST-Elevation Myocardial Infarction

Cited by 57 publications

References 93 publications

Randomized Trial of High Loading Dose of Clopidogrel for Reduction of Periprocedural Myocardial Infarction in Patients Undergoing Coronary Intervention

Randomized Trial of High Loading Dose of Clopidogrel for Reduction of Periprocedural Myocardial Infarction in Patients Undergoing Coronary Intervention

Platelet Activity, Coagulation, and Fibrinolysis During Exercise in Healthy Males

Long-term Outcomes of Regional Variations in Intensity of Invasive vs. Medical Management of Medicare Patients With Acute Myocardial Infarction

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