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Background In the ENGAGE AF-TIMI 48 trial, the higher-dose edoxaban (HDE) regimen had a similar incidence of ischaemic stroke compared with warfarin, whereas a higher incidence was observed with the lower-dose regimen (LDE). Amiodarone increases edoxaban plasma levels via P-glycoprotein inhibition. The current pre-specified exploratory analysis was performed to determine the effect of amiodarone on the relative efficacy and safety profile of edoxaban. Methods and results At randomization, 2492 patients (11.8%)were receiving amiodarone. The primary efficacy endpoint of stroke or systemic embolic eventwas significantly lower with LDE compared with war far in amiodarone treated patients vs. patients not on amiodarone (hazard ratio [HR] 0.60, 95% confidence intervals [CIs] 0.36-0.99 and HR 1.20, 95% CI 1.03-1.40, respectively; P interaction ,0.01). In patients randomized to HDE, no such interaction for efficacy was observed (HR 0.73, 95% CI 0.46-1.17 vs. HR 0.89, 95% CI 0.75-1.05, P interaction = 0.446). Major bleeding was similar in patients on LDE (HR 0.35, 95% CI 0.21-0.59 vs. HR 0.53, 95% CI 0.46-0.61, P interaction = 0.131) and HDE (HR 0.94, 95% CI 0.65-1.38 vs. HR 0.79, 95% CI 0.69-0.90, P interaction = 0.392) when compared with warfarin, independent of amiodarone use. Conclusions Patients randomized to the LDE treated with amiodarone at the time of randomization demonstrated a significant reduction in ischaemic events vs. warfarin when compared with those not on amiodarone, while preserving a favourable bleeding profile. In contrast, amiodarone had no effect on the relative efficacy and safety of HDE. [ABSTRACT FROM AUTHOR]

Context: Patients with unstable angina/non-ST-segment elevation myocardial infarction (MI) (UA/NSTEMI) present with a wide spectrum of risk for death and cardiac ischemic events.Objective: To develop a simple risk score that has broad applicability, is easily calculated at patient presentation, does not require a computer, and identifies patients with different responses to treatments for UA/NSTEMI.Design, Setting, and Patients: Two phase 3, international, randomized, double-blind trials (the Thrombolysis in Myocardial Infarction [TIMI] 11B trial [August 1996-March 1998] and the Efficacy and Safety of Subcutaneous Enoxaparin in Unstable Angina and Non-Q-Wave MI trial [ESSENCE; October 1994-May 1996]). A total of 1957 patients with UA/NSTEMI were assigned to receive unfractionated heparin (test cohort) and 1953 to receive enoxaparin in TIMI 11B; 1564 and 1607 were assigned respectively in ESSENCE. The 3 validation cohorts were the unfractionated heparin group from ESSENCE and both enoxaparin groups.Main Outcome Measures: The TIMI risk score was derived in the test cohort by selection of independent prognostic variables using multivariate logistic regression, assignment of value of 1 when a factor was present and 0 when it was absent, and summing the number of factors present to categorize patients into risk strata. Relative differences in response to therapeutic interventions were determined by comparing the slopes of the rates of events with increasing score in treatment groups and by testing for an interaction between risk score and treatment. Outcomes were TIMI risk score for developing at least 1 component of the primary end point (all-cause mortality, new or recurrent MI, or severe recurrent ischemia requiring urgent revascularization) through 14 days after randomization.Results: The 7 TIMI risk score predictor variables were age 65 years or older, at least 3 risk factors for coronary artery disease, prior coronary stenosis of 50% or more, ST-segment deviation on electrocardiogram at presentation, at least 2 anginal events in prior 24 hours, use of aspirin in prior 7 days, and elevated serum cardiac markers. Event rates increased significantly as the TIMI risk score increased in the test cohort in TIMI 11B: 4.7% for a score of 0/1; 8.3% for 2; 13. 2% for 3; 19.9% for 4; 26.2% for 5; and 40.9% for 6/7 (P<.001 by chi(2) for trend). The pattern of increasing event rates with increasing TIMI risk score was confirmed in all 3 validation groups (P<.001). The slope of the increase in event rates with increasing numbers of risk factors was significantly lower in the enoxaparin groups in both TIMI 11B (P =.01) and ESSENCE (P =.03) and there was a significant interaction between TIMI risk score and treatment (P =. 02).Conclusions: In patients with UA/NSTEMI, the TIMI risk score is a simple prognostication scheme that categorizes a patient's risk of death and ischemic events and provides a basis for therapeutic decision making. JAMA. 2000;284:835-842 [ABSTRACT FROM AUTHOR]

N-acetylcysreine (NAC) has been shown to potentiate the haemodynamic and antiplatelet effects of nitroglycerine (NTG) in man, and to limit the development of haemodynamic tolerance to NTG. These effects may be mediated by the formation of S-nitroso-NAC, which induces vasodilation and strongly inhibits platelet aggregation. In a randomized double-blind study in 46 patients with severe unstable angina pectoris unresponsive to standard treatment (including cutaneous nitrates and calcium antagonists in 45 patients) we compared the effects of intravenous (IV) NTG with those of IV NTG combined with IV NAC (5 g 6 hourly).Treatment with NTG/NAC (24 patients) was associated with a similar frequency of episodes of chest pain as treatment with NTG alone (22 patients), but somewhat fewer increments in infusion rate for pain control (10 vs 17; P NS). The NTG/NAC group had a significantly lower incidence of acute myocardial infarction than the NTG/placebo group (3 vs 10 patients; P = 0·013).Symptomatic hypotension occurred frequently in the NTG/NAC group (7 vs 0 patients; P = 0·006). It is concluded that combined administration of NTG and NAC in patients with unstable angina pecroris may augment the clinical efficacy of NTG, largely by reducing the incidence of acute myocardial infarction. However, the high incidence of severe hypotension with NTG/NAC suggests that this regimen should be used with some caution. [ABSTRACT FROM PUBLISHER]

An elderly man developed cardiac tamponade from a tuberculous pericardial effusion but without such typical manifestations as pulsus paradoxus and jugular-vein distension. This case illustrates the difficulties in clinical recognition of low-pressure cardiac tamponade, which can develop in the presence of dehydration and hypovolemia. The hemodynamic factors that account for this phenomenon are discussed. [ABSTRACT FROM AUTHOR]