Troponin T Identifies Patients With Unstable Coronary Artery Disease Who Benefit From Long-Term Antithrombotic Protection fn1fn1This study was supported by grants from the Swedish Heart and Lung Foundation, Stockholm, Sweden; the Selander’s Foundation, Uppsala, Sweden; the Uppsala County Association Against Heart and Lung Diseases, Uppsala, Sweden; Pharmacia Biosensor AB, Uppsala, Sweden; and Pharmacia AB, Stockholm, Sweden. Boehringer Mannheim Scandinavia AB, Bomma, Sweden provided the troponin T kits.

AbstractObjectives. We sought to evaluate whether troponin T might be used for identification of patients with unstable coronary artery disease in whom treatment with low molecular weight heparin is beneficial.Background. Early identification of subgroups with differences in response to a certain treatment is important to optimize the utilization of different therapeutic approaches.Methods. Nine-hundred seventy-one patients with unstable coronary artery disease who participated in a trial of the low molecular weight heparin dalteparin (Fragmin) and who provided blood samples were classified into subgroups according to troponin T level. In the short-term phase all patients received subcutaneous dalteparin/placebo twice daily for 6 days. During the long-term phase they continued with daltparin/placebo once daily for another 5 weeks.Results. In the short-term phase, dalteparin reduced the incidence of death or myocardial infarction from 2.4% to 0% (p = 0.12) and from 6.0% to 2.5% (p < 0.05) in 327 and 644 patients with troponin T levels <0.1 and ≥0.1 μg/liter, respectively. During long-term treatment there was an increasing difference between the placebo and dalteparin group in those with troponin T levels ≥0.1 μg/liter, in whom the incidences at 40 days were 14.2% and 7.4%, respectively (p < 0.01). In contrast, no beneficial effect of the long-term treatment could be demonstrated in those with troponin T levels <0.1 μg/liter (4.7% vs. 5.7%).Conclusions. Elevation of troponin T identifies a subgroup of patients in whom prolonged antithrombotic treatment (e.g., with dalteparin) is beneficial.(J Am Coll Cardiol 1997;29:43–8)

Is early invasive treatment of unstable coronary artery disease equally effective for both women and men?

AbstractBACKGROUNDThe Fragmin and fast Revascularization during InStability in Coronary artery disease (FRISC II) trial compared the effectiveness of an early invasive versus a noninvasive strategy in terms of the incidence of death and myocardial infarction (MI) in patients with unstable coronary artery disease (CAD).OBJECTIVESIn this subanalysis, we sought to evaluate gender differences in the effect of these different strategies.METHODSThe patients (749 women and 1,708 men) were randomized to early invasive or noninvasive strategies. Coronary angiography was performed within the first 7 days in 96% and 10% of the invasive and noninvasive groups, respectively, and revascularization was performed within the first 10 days in 71% and 9% of the invasive and noninvasive groups, respectively.RESULTSWomen presenting with unstable CAD were older, but fewer had previous infarctions, left ventricular dysfunction and elevated troponin T levels. Women had fewer angiographic changes. There was no difference in MI or death at 12 months among women in the invasive and noninvasive groups (12.4% vs. 10.5%, respectively), in contrast to the favorable effect in the invasively treated group of men (9.6% vs. 15.8%, p < 0.001). In an interaction analysis, there was a different effect of the early invasive strategy for the two genders (p = 0.008).CONCLUSIONSWomen with symptoms and/or signs of unstable CAD are older, but still have less severe CAD and a better prognosis compared with men. In contrast to its beneficial effect in men, an early invasive strategy did not reduce the risk of future events among women. Further research is warranted to identify the most appropriate treatment strategy in women with unstable CAD

International differences in treatment effect: do they really exist and why?

With the increasing globalization of clinical trials, the opportunity exists to explore potential geographic differences in treatment effect within any major trial. Such geographic differences may arise because of international differences in patient selection, medical practice, or evaluation of outcomes, and such international variations need better documentation in trial reports. Appropriate pre-defined statistical analyses, including statistical tests of interaction regarding geographic heterogeneity in treatment effect, are important. Geographic variations are a particularly tricky form of subgroup analysis: they lack statistical power, are at best hypothesis-generating and can generate more confusion than insight. Referring to key examples, e.g. the PLATO and MERIT-HF, we emphasize the need for caution in interpreting evidence of potential geographic inconsistencies in treatment effect. Although it is appropriate to explore any biological or practical reasons for apparent geographic anomalies in treatment effect, the play of chance is often the most plausible and wise interpretation

A long-term perspective on the protective effects of an early invasive strategy in unstable coronary artery disease Two-year follow-up of the FRISC-II invasive study

AbstractObjectivesWe sought to report the first and repeat events and to separate spontaneous and procedure-related events over two years in the Fast Revascularization during InStability in Coronary artery disease (FRISC-II) invasive trial.BackgroundThe FRISC-II invasive trial compared the long-term effects of an early invasive versus noninvasive strategy, in terms of death and myocardial infarction (MI) and the need for repeat hospital admissions and late revascularization procedures in patients with coronary artery disease (UCAD).MethodsIn the FRISC-II trial, 2,457 patients with UCAD were randomized to an early invasive or noninvasive strategy.ResultsAt 24 month follow-up, there were reductions in mortality (n = 45 [3.7%] vs. 67 [5.4%]; risk ratio 0.68 [95% confidence interval (CI) 0.47 to 0.98]; p = 0.038), MI (n = 111 [9.2%] vs. 156 [12.7%]; risk ratio 0.72 [95% CI 0.57 to 0.91]; p = 0.005), and the composite end point of death or MI (n = 146 [12.1%] vs. 200 [16.3%]; risk ratio 0.74 [95% CI 0.61 to 0.90]; p = 0.003) in the invasive compared with the noninvasive group. Procedure-related MIs were two to three times more common, but spontaneous ones were three times less common in the invasive than in the noninvasive group. After the first year, there was no difference in mortality (n = 20 [1.7%]) between the two groups and fewer MIs in the invasive group (p = 0.031).ConclusionsIn UCAD, the early invasive approach leads to a sustained reduction in mortality, cardiac morbidity, and the need for repeat hospital admissions and late revascularization procedures. Although the benefits are greatest during the first months, during the second year, cardiac morbidity is lower and the need for hospital care is less in the invasive group

In situ etching for total control over axial and radial nanowire growth

We report a method using in situ etching to decouple the axial from the radial nanowire growth pathway, independent of other growth parameters. Thereby a wide range of growth parameters can be explored to improve the nanowire properties without concern of tapering or excess structural defects formed during radial growth. We demonstrate the method using etching by HCl during InP nanowire growth. The improved crystal quality of etched nanowires is indicated by strongly enhanced photoluminescence as compared to reference nanowires obtained without etching

Balancing the Benefits and Risks of 2 Doses of Dabigatran Compared With Warfarin in Atrial Fibrillation

ObjectivesThis study sought to compare the net clinical benefit of dabigatran 110 mg bid and 150 mg bid with that of warfarin in patients with atrial fibrillation (AF).BackgroundIn patients with AF, dabigatran 110 mg bid and 150 mg bid are associated with similar rates of death. However, the higher dose reduces ischemic stroke and increases bleeding compared with the lower dose. Therefore, there is uncertainty about how to evaluate the overall benefit of the 2 doses.MethodsIn 18,113 AF patients in the RE-LY (Randomized Evaluation of Long Term Anticoagulant Therapy) trial, we used a previously developed method for integrating ischemic and bleeding events as “ischemic stroke equivalents” in order to compare a weighted benefit of 2 doses of dabigatran with each other, and with that of warfarin.ResultsCompared with warfarin, there was a significant decrease in ischemic stroke equivalents with both dabigatran doses: –0.92 per 100 patient years (95% confidence interval [CI]: –1.74 to −0.21, p = 0.02) with dabigatran 110 mg bid and –1.08 (95% CI: –1.86 to −0.34, p = 0.01) with dabigatran 150 mg bid. There was no significant difference in ischemic stroke equivalents between the 2 doses: –0.16 (95% CI: –0.80 to 0.43) comparing dabigatran 150 mg bid with 110 bid. When including death in the weighted benefit calculations, the results were similar.ConclusionsOn a group level both doses of dabigatran as compared with warfarin have similar benefits when considering a weighted estimate including both efficacy and safety. The similar overall benefits of the 2 doses of dabigatran versus warfarin support individualizing the dose based on patient characteristics and physician and patient preferences. (Randomized Evaluation of Long Term Anticoagulant Therapy [RE-LY] With Dabigatran Etexilate; NCT00262600

Low molecular weight heparin (dalteparin) as adjuvant treatment to thrombolysis in acute myocardial infarction—a pilot study: Biochemical Markers in Acute Coronary Syndromes (BIOMACS II)

AbstractOBJECTIVESThis randomized, double blind, placebo-controlled pilot trial evaluated the effect of dalteparin as an adjuvant to thrombolysis in patients with acute myocardial infarction regarding early reperfusion, recurrent ischemia and patency at 24 h.BACKGROUNDLow-molecular-weight heparin, given subcutaneously twice daily without monitoring, might be an attractive alternative to conventional intravenous heparin in the treatment of acute myocardial infarction.METHODSIn 101 patients dalteparin/placebo 100 IU/kg was given just before streptokinase and a second injection 120 IU/kg after 12 h. Monitoring with continuous vector-ECG was done to obtain signs of early reperfusion and later ischemic episodes. Blood samples for myoglobin were obtained at start and after 90 min to evaluate signs of reperfusion. Coronary angiography was performed after 20–28 h to evaluate TIMI-flow in the infarct-related artery.RESULTSDalteparin added to streptokinase tended to provide a higher rate of TIMI grade 3 flow in infarct-related artery compared to placebo, 68% versus 51% (p = 0.10). Dalteparin had no effects on noninvasive signs of early reperfusion. In patients with signs of early reperfusion, there seemed to be a higher rate of TIMI grade 3 flow, 74% versus 46% (myoglobin) (p = 0.04) and 73% versus 52% (vector-ECG) (p = 0.11). Ischemic episodes 6–24 h. after start of treatment were fewer in the dalteparin group, 16% versus 38% (p = 0.04).CONCLUSIONSWhen dalteparin was added as an adjuvant to streptokinase and aspirin, there were tendencies for less ECG monitoring evidence of recurrent ischemia and better patency at 24 h, warranting further study