Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) 11B trial. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. Comparison of two treatment durations (6 days and 14 days) of a low molecular weight heparin with a 6-day treatment of unfractionated heparin in the initial management of unstable angina or non-Q wave myocardial infarction: FRAX.I.S. (FRAxiparine in Ischaemic Syndrome). [Comparison of low-molecular-weight heparin and unfractionated heparin in the treatment of unstable angina]. Low molecular weight heparin versus regular heparin or aspirin in the treatment of unstable angina and silent ischemia. Comparison of clinical outcome of fixed-dose subcutaneous low molecular weight heparin (tinzaparin) with conventional heparin in unstable angina: a pilot study.
Low-molecular-weight heparins are attractive alternatives to unfractionated heparin (UFH) for management of unstable angina/non-Q-wave myocardial infarction (UA/NQMI).
                Patients (n=3910) with UA/NQMI were randomized to intravenous UFH for >/=3 days followed by subcutaneous placebo injections or uninterrupted antithrombin therapy with enoxaparin during both the acute phase (initial 30 mg intravenous bolus followed by injections of 1.0 mg/kg every 12 hours) and outpatient phase (injections every 12 hours of 40 mg for patients weighing <65 kg and 60 mg for those weighing >/=65 kg). The primary end point (death, myocardial infarction, or urgent revascularization) occurred by 8 days in 14.5% of patients in the UFH group and 12.4% of patients in the enoxaparin group (OR 0.83; 95% CI 0.69 to 1.00; P=0. 048) and by 43 days in 19.7% of the UFH group and 17.3% of the enoxaparin group (OR 0.85; 95% CI 0.72 to 1.00; P=0.048). During the first 72 hours and also throughout the entire initial hospitalization, there was no difference in the rate of major hemorrhage in the treatment groups. During the outpatient phase, major hemorrhage occurred in 1.5% of the group treated with placebo and 2.9% of the group treated with enoxaparin (P=0.021).
                Enoxaparin is superior to UFH for reducing a composite of death and serious cardiac ischemic events during the acute management of UA/NQMI patients without causing a significant increase in the rate of major hemorrhage. No further relative decrease in events occurred with outpatient enoxaparin treatment, but there was an increase in the rate of major hemorrhage. Antithrombotic therapy with heparin plus aspirin reduces the rate of ischemic events in patients with unstable coronary artery disease. Low-molecular-weight heparin has a more predictable anticoagulant effect than standard unfractionated heparin, is easier to administer, and does not require monitoring.
                In a double-blind, placebo-controlled study, we randomly assigned 3171 patients with angina at rest or non-Q-wave myocardial infarction to receive either 1 mg of enoxaparin (low-molecular-weight heparin) per kilogram of body weight, administered subcutaneously twice daily, or continuous intravenous unfractionated heparin. Therapy was continued for a minimum of 48 hours to a maximum of 8 days, and we collected data on important coronary end points over a period of 30 days.
                At 14 days the risk of death, myocardial infarction, or recurrent angina was significantly lower in the patients assigned to enoxaparin than in those assigned to unfractionated heparin (16.6 percent vs. 19.8 percent, P=0.019). At 30 days, the risk of this composite end point remained significantly lower in the enoxaparin group (19.8 percent vs. 23.3 percent, P=0.016). The need for revascularization procedures at 30 days was also significantly less frequent in the patients assigned to enoxaparin (27.1 percent vs. 32.2 percent, P=0.001). The 30-day incidence of major bleeding complications was 6.5 percent in the enoxaparin group and 7.0 percent in the unfractionated-heparin group, but the incidence of bleeding overall was significantly higher in the enoxaparin group (18.4 percent vs. 14.2 percent, P=0.001), primarily because of ecchymoses at injection sites.
                Antithrombotic therapy with enoxaparin plus aspirin was more effective than unfractionated heparin plus aspirin in reducing the incidence of ischemic events in patients with unstable angina or non-Q-wave myocardial infarction in the early phase. This benefit of enoxaparin was achieved with an increase in minor but not in major bleeding. To assess the benefit of short-term low molecular weight heparin nadroparin compared with unfractionated heparin in unstable angina or non-Q wave myocardial infarction patients and to determine whether a longer, 2-week low molecular weight heparin regimen would offer additional clinical benefit.
                This was a multicentre, prospective, randomized, double-blind study in three parallel groups, involving 3468 patients. Patients received one of three treatment regimens: the unfractionated heparin group received an intravenous bolus of unfractionated heparin 5000 IU, followed by an activated partial thromboplastin time adjusted infusion of unfractionated heparin for 6+/-2 days; the nadroparin 6 group received an intravenous bolus of nadroparin 86 anti-Xa IU. kg(-1), followed by twice daily subcutaneous injections of nadroparin 86 anti-Xa IU. kg(-1)for 6+/-2 days, and the nadroparin 14 group received an intravenous bolus of nadroparin 86 anti-Xa IU. kg(-1), followed by twice daily subcutaneous injections of nadroparin 86 anti-Xa IU. kg(-1)for 14 days. No statistically significant differences were observed between the three treatment regimens with respect to the primary outcome (cardiac death, myocardial infarction, refractory angina, or recurrence of unstable angina at day 14). The absolute differences between the groups in the incidence of the primary outcome were: -0.3% (P=0.85) for the nadroparin 6 group vs the unfractionated heparin group and +1.9% (P=0.24) for the nadroparin 14 group vs the unfractionated heparin group. Furthermore, there were no significant intergroup differences regarding any of the secondary efficacy outcomes. However, there was an increased risk of major haemorrhages in the nadroparin 14 group compared with unfractionated heparin (3.5% vs 1.6%;P=0.0035).
                Treatment with nadroparin for 6+/-2 days provides similar efficacy and safety to treatment with unfractionated heparin, for the same period, in the therapeutic management of acute unstable angina or non-Q wave myocardial infarction, and may be easier to administer. A prolonged regimen of nadroparin (14 days) does not provide any additional clinical benefit. Low molecular weight heparin can be administered by the subcutaneous route and has a stable and prolonged antithrombotic effect. These features have prompted clinical essays about its use as an alternative to unfractionated heparin in the treatment of unstable angina.
                To compare the clinical effects of low molecular weight heparin and unfractionated conventional heparin in patients with unstable angina or non Q infarction.
                Seventy patients (47 male) admitted to the hospital with the diagnosis of unstable angina or non Q acute myocardial infarction were randomly assigned to receive unfractionated intravenous heparin or subcutaneous low molecular weight heparin bid. All received aspirin p.o. and i.v. nitroglycerin. The incidence of recurrent angina, acute myocardial infarction or a need for emergency surgical revascularization during hospital stay were assessed in both groups.
                Compared to patients with low molecular weight heparin, patients receiving unfractionated heparin had a higher incidence of recurrent resting angina (23 and 47.5% respectively, p < 0.04) and higher need for emergency surgical revascularization (3.3 and 17.5% respectively, p < 0.06). Patients treated with unfractionated conventional heparin had a 3 times higher risk of having an adverse cardiovascular event than patients receiving low molecular weight heparin (O.R. 0.33, confidence intervals 0.11-0.58).
                Low molecular weight heparin is superior to unfractionated conventional heparin in the treatment of unstable angina and non Q acute myocardial infarction. This study was designed to test the hypothesis that low molecular weight heparin may lessen the severity of ischemic events in patients with unstable angina.
                Unstable angina is a thrombotic process that requires intensive medical treatment. Although current treatments can reduce the number of complications, serious bleeding continues to occur. Nadroparin calcium, a low molecular weight heparin, seems to be a safe therapeutic agent that does not require laboratory monitoring.
                A total of 219 patients with unstable angina entered the study at a mean time of 6.17 h after the last episode of rest pain. Patients were randomized to receive aspirin (200 mg/day [group A]), aspirin plus regular heparin (400 IU/kg body weight per day intravenously and titered by activated partial thromboplastin time [group B]) and aspirin plus low molecular weight heparin (214 UIC/kg anti-Xa twice daily subcutaneously [group C]). The major end points determined for the in-hospital period were 1) recurrent angina, 2) myocardial infarction, 3) urgent revascularization, 4) major bleeding, and 5) death. Minor end points were 1) silent myocardial ischemia, and 2) minor bleeding. Event rates were tested by chi-square analysis.
                Recurrent angina occurred in 37%, 44% and 21% of patients in groups A, B and C, respectively, and was significantly less frequent in group C than in either group A (odds ratio 2.26, 95% confidence interval [CI] 1 to 5.18, p = 0.03) or group B (odds ratio, 3.07, 95% CI 1.36 to 7.00, p = 0.002). Nonfatal myocardial infarction was present in seven patients in group A, four in group B and none in group C (group B vs. A, p = 0.5; group C vs. A, p = 0.01). Urgent revascularization was performed in nine patients in group A, seven in group B and one in group C (C vs. A, p = 0.01). Two episodes of major bleeding occurred in group B. Silent myocardial ischemia was present in 38%, 41% and 25% of patients in groups A, B and C, respectively, and was significantly less frequent in group C than group B (odds ratio 2.12, 95% CI 0.97 to 4.69, p = 0.04). Minor bleeding was detected in 10 patients in group B, 1 patient in group C (B vs. C, p = 0.01) and no patient in group A (A vs. B, p = 0.003).
                In this study, treatment with aspirin plus a high dose of low molecular weight heparin during the acute phase of unstable angina was significantly better than treatment with aspirin alone or aspirin plus regular heparin. Forty patients who were hospitalized for unstable angina were randomized to receive treatment with either regular heparin (Group I) in conventional dose as continuous infusion for 5 days or fixed-dose low molecular weight heparin (LMWH) (Group II), 3500 units subcutaneous twice daily for a period of 5 days. Both the groups were evenly matched with regard to age, sex presence of risk factors and adjunctive drug therapy. The clinical endpoints at the end of 5 day therapy were: recurrence of angina, occurrence of myocardial infarction and need for urgent revascularization. In Group I, 6 out of 20 patients had recurrence of angina, of whom 3 required urgent coronary angiography and revascularization. In Group II, 4 out of 20 patients had recurrence of angina, of whom one patient required urgent angiography and angioplasty. There were no bleeding complications in either of the groups. The recurrent anginal episodes in the conventional heparin group correlated with low aPTT values at the time of angina. Thus, this pilot study suggests that LMWH is equally effective in the treatment of unstable angina, the advantage of LMWH being the ease of administration and no need for monitoring aPTT levels during therapy.
LMWH and UFH had similar risk of mortality, recurrent angina, and major or minor bleeding but LMWH had decreased risk of MI, revascularization and thrombocytopenia. New trials with longer follow up are required.