N Engl J Med. 1998 May 21;338(21):1498-505. doi: 10.1056/NEJM199805213382103.
Activation of platelets is central to the pathophysiology of unstable angina. We studied whether inhibition of the final common pathway for platelet aggregation with tirofiban, a nonpeptide glycoprotein IIb/IIIa receptor antagonist, would improve clinical outcome in this condition.
In a double-blind study, we randomly assigned 3232 patients who were already receiving aspirin to additional treatment with intravenous tirofiban for 48 hours. The primary end point was a composite of death, myocardial infarction, or refractory ischemia at 48 hours.
The incidence of the composite end point was 32 percent lower at 48 hours in the group that received tirofiban (3.8 percent, vs. 5.6 percent with heparin; risk ratio, 0.67; 95 percent confidence interval, 0.48 to 0.92; P=0.01). Percutaneous revascularization was performed in 1.9 percent of the patients during the first 48 hours. At 30 days, the frequency of the composite end point (with the addition of readmission for unstable angina) was similar in the two groups (15.9 percent in the tirofiban group vs. 17.1 percent in the heparin group, P=0.34). There was a trend toward a reduction in the rate of death or myocardial infarction with tirofiban (a rate of 5.8 percent, as compared with 7.1 percent in the heparin group; risk ratio, 0.80; 95 percent confidence interval, 0.61 to 1.05; P=0.11), and mortality was 2.3 percent, as compared with 3.6 percent in the heparin group (P=0.02). Major bleeding occurred in 0.4 percent of the patients in both groups. Reversible thrombocytopenia occurred more frequently with tirofiban than with heparin (1.1 percent vs. 0.4 percent, P=0.04).
Tirofiban was generally well tolerated and, as compared with heparin, reduced ischemic events during the 48-hour infusion period, during which revascularization procedures were not performed. The incidence of refractory ischemia and myocardial infarction was not reduced at 30 days, but mortality was lower among the patients given tirofiban. Platelet inhibition with aspirin plus tirofiban may have a role in the management of unstable angina.
血小板激活在不稳定型心绞痛的病理生理学中起核心作用。我们研究了用非肽类糖蛋白IIb/IIIa受体拮抗剂替罗非班抑制血小板聚集的最终共同途径是否会改善这种情况下的临床结局。
在一项双盲研究中，我们将3232例已接受阿司匹林治疗的患者随机分配，使其接受静脉注射替罗非班额外治疗48小时。主要终点是48小时时死亡、心肌梗死或难治性缺血的复合终点。
接受替罗非班治疗的组在48小时时复合终点的发生率降低了32%（3.8%，肝素组为5.6%；风险比为0.67；95%置信区间为0.48至0.92；P = 0.01）。在最初48小时内，1.9%的患者接受了经皮血管重建术。30天时，两组复合终点（加上因不稳定型心绞痛再次入院）的发生率相似（替罗非班组为15.9%，肝素组为17.1%，P = 0.34）。替罗非班有降低死亡或心肌梗死发生率的趋势（发生率为5.8%，肝素组为7.1%；风险比为0.80；95%置信区间为0.61至1.05；P = 0.11），死亡率为2.3%，肝素组为3.6%（P = 0.02）。两组均有0.4%的患者发生大出血。替罗非班组可逆性血小板减少症的发生率高于肝素组（1.1%对0.4%，P = 0.04）。
替罗非班总体耐受性良好，与肝素相比，在未进行血管重建术的48小时输注期内减少了缺血事件。30天时难治性缺血和心肌梗死的发生率未降低，但接受替罗非班治疗的患者死亡率较低。阿司匹林加替罗非班抑制血小板可能在不稳定型心绞痛的治疗中发挥作用。
