Combination antithrombotic therapy in unstable rest angina and non-Q-wave infarction in nonprior aspirin users. Primary end points analysis from the ATACS trial. Antithrombotic Therapy in Acute Coronary Syndromes Research Group. Usefulness of antithrombotic therapy in resting angina pectoris or non-Q-wave myocardial infarction in preventing death and myocardial infarction (a pilot study from the Antithrombotic Therapy in Acute Coronary Syndromes Study Group). Randomized trial comparing intravenous nitroglycerin and heparin for treatment of unstable angina secondary to restenosis after coronary artery angioplasty. Low molecular weight heparin versus regular heparin or aspirin in the treatment of unstable angina and silent ischemia. Comparison of the effect of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina. Aspirin, heparin, or both to treat acute unstable angina.
The purpose of this study was to compare combination antithrombotic therapy with aspirin plus anticoagulation versus aspirin alone, when added to conventional antianginal therapy in patients with unstable rest angina or non-Q-wave myocardial infarction who were nonprior aspirin users.
                Two hundred fourteen patients were randomized; 109 were randomized to receive aspirin alone (162.5 mg daily) and 105 to receive a combination of aspirin plus anticoagulation, ie, aspirin 162.5 mg daily plus heparin (activated partial thromboplastin time, two times control) followed by aspirin 162.5 mg daily plus warfarin (international normalized ratio, 2 to 3). Trial therapy was begun by 9.5 +/- 8.8 hours of qualifying pain and was continued for 12 weeks. Primary end points were recurrent angina with ECG changes, myocardial infarction, and/or death. Analysis by intention to treat of primary events at 12 weeks was performed. At 14 days, there was a significant reduction in total ischemic events in the combination group versus aspirin alone (10.5% versus 27%, P = .004). An efficacy analysis of primary events at 12 weeks also revealed a large reduction in total ischemic events in the combination group versus aspirin alone (13% versus 25%, P = .06). Bleeding complications were slightly more common with combination therapy.
                In nonprior aspirin users, combination antithrombotic therapy with aspirin plus anticoagulation significantly reduces recurrent ischemic events in the early phase of unstable angina. In a prospective pilot trial of antithrombotic therapy in the acute coronary syndromes (ATACS) of resting and unstable angina pectoris or non-Q-wave myocardial infarction, 3 different antithrombotic regimens in the prevention of recurrent ischemic events were compared for efficacy. Ninety-three patients were randomized to receive aspirin (325 mg/day), or full-dose heparin followed by warfarin, or the combination of aspirin (80 mg/day) plus heparin and then warfarin. Trial antithrombotic therapy was added to standardized antianginal medication and continued for 3 months or until an end point was reached. Analysis, by intention-to-treat, of the 3-month end points, revealed the following: recurrent ischemia occurred in 7 patients (22%) after aspirin, in 6 patients (25%) after heparin and warfarin, and in 16 patients (43%) after aspirin combined with heparin and then warfarin; coronary revascularization occurred in 12 patients (38%) after aspirin, in 12 patients (50%) after heparin and warfarin, and in 22 patients (60%) after aspirin combined with heparin and then warfarin; myocardial infarction occurred in 1 patient (3%) after aspirin, in 3 patients (13%) after heparin and warfarin, and in no patient after aspirin combined with heparin and then warfarin; no deaths occurred after aspirin or after aspirin combined with heparin and then warfarin, but 1 patient (4%) died after warfarin alone; major bleeding occurred in 3 patients (9%) after aspirin, in 2 patients (8%) after heparin and warfarin, and in 3 patients (8%) after aspirin combined with heparin and then warfarin. Recurrent myocardial ischemia occurred at 3 +/- 3 days after randomization.(ABSTRACT TRUNCATED AT 250 WORDS) The treatment of unstable angina targets the specific pathophysiological thrombotic process at the site of the active culprit lesion. In unstable angina due to a restenotic lesion, smooth muscle cell proliferation and increased vasoreactivity may play a more important role than thrombus formation. Therefore, the relative benefits of nitroglycerin and heparin might differ in unstable angina associated with restenosis compared with classic unstable angina.
                We randomized 200 patients hospitalized for unstable angina within 6 months after angioplasty (excluding those with intracoronary stents) to double-blind administration of intravenous nitroglycerin, heparin, their combination, or placebo for 63+/-30 hours. Recurrent angina occurred in 75% of patients in the placebo and heparin-alone groups, compared with 42.6% of patients in the nitroglycerin-alone group and 41.7% of patients in the nitroglycerin-plus-heparin group (P<0.003). Refractory angina requiring angiography occurred in 22.9%, 29.2%, 4. 3%, and 4.2% of patients, respectively (P<0.002). The odds ratios for being event free were 0.24 (95% CI, -0.13 to 0.45, P=0.0001) for nitroglycerin versus no nitroglycerin and 0.98 (95% CI, -0.55 to 1. 73, P=NS) for heparin versus no heparin. No patient died or suffered myocardial infarction.
                Intravenous nitroglycerin is highly effective in preventing adverse ischemic events (recurrent or refractory angina) in patients with unstable angina secondary to restenosis, whereas heparin has no effect. 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. This study compared the effects of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina.
                Transient myocardial ischemia occurring in patients with unstable angina is associated with an adverse prognosis. Heparin and aspirin are two drugs used frequently in the treatment of this condition, but the effect of combination therapy versus aspirin alone on transient myocardial ischemia is unknown.
                Two hundred eighty-five consecutive patients with unstable angina were randomized to receive either intravenous heparin plus oral aspirin (150 mg once daily) (Group H + A) or aspirin alone (Group A). Patients also received a beta-adrenergic blocking agent, diltiazem and intravenous nitrates. ST segment monitoring was performed for the 1st 48 h of treatment. Patients were followed up for the duration of their in-hospital stay.
                One hundred fifty-four patients (30 women, mean [+/- SEM] age 58.3 +/- 0.8 years) received heparin and aspirin (Group H + A), and 131 patients (26 women, mean age 60.6 +/- 0.8 years) received aspirin only (Group A). ST segment monitoring (11,622 h) yielded 244 episodes of transient myocardial ischemia of a total duration of 7,819 min. There were no significant differences between the two treatment arms in the number of patients with transient myocardial ischemia (27 [18%] in Group H + A vs. 31 [24%] in Group A), number of episodes (96 in Group H + A vs. 148 in Group A) or total duration of transient myocardial ischemia (2,911 min in Group H + A vs. 4,908 min in Group A). The incidence of in-hospital myocardial infarction or death was significantly higher in patients with transient myocardial ischemia (53% vs. 22%, p < 0.0001). Five of the six deaths occurred in patients with transient myocardial ischemia. Event-free survival from myocardial infarction or death was similar in both treatment groups. Preadmission therapy with aspirin was associated with a lower in-hospital infarction rate (19% vs. 34%, p = 0.01).
                The presence of transient myocardial ischemia in patients with unstable angina is associated with a significantly higher incidence of myocardial infarction or death in hospital. Combined therapy with heparin and aspirin compared with aspirin alone makes no difference in the development of these events, nor does it reduce the development of transient myocardial ischemia. We tested the usefulness of aspirin (325 mg twice daily), heparin (1000 units per hour by intravenous infusion), and a combination of the two in the early management of acute unstable angina pectoris in a double-blind, randomized, placebo-controlled trial involving 479 patients. The patients entered the study as soon as possible after hospital admission (at a mean [+/- SD] of 7.9 +/- 8.0 hours after the last episode of pain), and the study was ended after 6 +/- 3 days, when definitive therapy had been selected. Major end points--refractory angina, myocardial infarction, and death--occurred in 23, 12, and 1.7 percent of the 118 patients receiving placebo, respectively. Heparin was associated with a decrease in the occurrence of refractory angina (P = 0.002). The incidence of myocardial infarction was significantly reduced in the groups receiving aspirin (3 percent; P = 0.01), heparin (0.8 percent; P less than 0.001), and aspirin plus heparin (1.6 percent, P = 0.003), and no deaths occurred in these groups. There were too few deaths overall to permit evaluation of the effect of treatment on this end point. The combination of aspirin and heparin had no greater protective effect than heparin alone but was associated with slightly more serious bleeding (3.3 vs. 1.7 percent). We conclude that in the acute phase of unstable angina, either aspirin or heparin treatment is associated with a reduced incidence of myocardial infarction, and there is a trend favoring heparin over aspirin. Heparin treatment is also associated with a reduced incidence of refractory angina.
Compared to placebo, patients treated with heparins had similar risk of mortality, revascularization, recurrent angina, major bleeding and thrombocytopenia. However, those treated with heparins had decreased risk of MI and a higher incidence of minor bleeding.