Lette J, Tatum J L, Fraser S, Miller D D, Waters D D, Heller G, Stanton E B, Bom H S, Leppo J, Nattel S
Maisonneuve Hospital, Montreal, Quebec, Canada.
J Nucl Cardiol. 1995 Jan-Feb;2(1):3-17. doi: 10.1016/s1071-3581(05)80003-0.
Dipyridamole imaging is widely used as an alternative to exercise testing to identify and risk stratify patients with coronary artery disease. Safety data on intravenous dipyridamole stress testing has been derived largely from individual institutional data.
Data were collected retrospectively by 85 coinvestigators from 73,806 patients who underwent intravenous dipyridamole stress imaging in 59 hospitals and 19 countries to determine the incidence of major adverse reactions during testing. The dose of dipyridamole infused was 0.56 mg/kg in 64,740 patients, 0.74 mg/kg in 6551 patients, and 0.84 mg/kg in 2515 patients. Combined major adverse events among the entire 73,806 patients included seven cardiac deaths (0.95 per 10,000), 13 nonfatal myocardial infarctions (1.76 per 10,000), six nonfatal sustained ventricular arrhythmias (0.81 per 10,000) (ventricular tachycardia in two and ventricular fibrillation in four), nine transient cerebral ischemic attacks (1.22 per 10,000), (with speech or motor deficit), one stroke, and nine severe bronchospasms (1.22 per 10,000) (one intubation and eight near intubations). In addition to the safety data, detailed demographic, peripheral hemodynamic, side effect, and concomitant drug data were examined in a subgroup of 3751 patients. End points from subsets of patients were compared with those of the group as a whole. Multivariate analysis revealed that dipyridamole-induced chest pain was more common in patients less than 70 years old (p = 0.0017), those with a history of coronary revascularization (p = 0.002), or patients taking aspirin (p = 0.0001). Minor noncardiac side effects were less frequent among the elderly (p = 0.0053) and more frequent in women (p = 0.0001) and patients taking maintenance aspirin (p = 0.0034). When a patient was judged on the basis of the adequacy of hemodynamic response to be a dipyridamole "nonresponder" (< 10 mm Hg drop in systolic blood pressure and 10 beats/min increase in heart rate), the only significant predictor was angiotensin-converting enzyme inhibitor intake (p = 0.0025). Inferoposterior hypoperfusion was significantly more frequent in patients with dipyridamole-induced hypotension: 57% (44/77) (p < 0.0001) of those who had hypotension and 89% (8/9) (p = 0.0076) who had severe symptomatic bradyarrhythmias displayed inferoposterior defects on thallium scanning. Caffeine levels were determined in 391 consecutive patients: levels greater than 5 mg/L were observed in only eight patients (2%), suggesting that methylxanthine levels sufficient to alter the hemodynamic response to dipyridamole resulting in suboptimal hyperemic stress are unlikely when patients take nothing by mouth after midnight.
The risk of serious dipyridamole-induced side effects is very low and is comparable to that reported for exercise testing in a similar patient population.
双嘧达莫成像被广泛用作运动试验的替代方法，以识别冠心病患者并对其进行风险分层。静脉注射双嘧达莫负荷试验的安全性数据主要来自个别机构的数据。
85名共同研究者对来自19个国家59家医院的73806例接受静脉注射双嘧达莫负荷成像的患者进行了回顾性数据收集，以确定试验期间主要不良反应的发生率。64740例患者双嘧达莫的输注剂量为0.56mg/kg，6551例患者为0.74mg/kg，2515例患者为0.84mg/kg。在全部73806例患者中，合并的主要不良事件包括7例心源性死亡（每10000例中有0.95例）、13例非致死性心肌梗死（每10000例中有1.76例）、6例非致死性持续性室性心律失常（每10000例中有0.81例）（2例室性心动过速，4例心室颤动）、9例短暂性脑缺血发作（每10000例中有1.22例）（伴有言语或运动功能缺损）、1例中风和9例严重支气管痉挛（每10000例中有1.22例）（1例插管，8例接近插管）。除安全性数据外，还对3751例患者的亚组进行了详细的人口统计学、外周血流动力学、副作用和伴随用药数据检查。将患者亚组的终点与整个组的终点进行比较。多因素分析显示，双嘧达莫诱发的胸痛在70岁以下患者（p=0.0017）、有冠状动脉血运重建史的患者（p=0.002）或服用阿司匹林的患者（p=0.0001）中更常见。轻微的非心脏副作用在老年人中较少见（p=0.0053），在女性（p=0.0001）和服用维持剂量阿司匹林的患者（p=0.0034）中更常见。当根据血流动力学反应是否充分判断患者为双嘧达莫“无反应者”（收缩压下降<10mmHg，心率增加<10次/分钟）时，唯一显著的预测因素是血管紧张素转换酶抑制剂的使用（p=0.0025）。双嘧达莫诱发低血压的患者下后壁灌注不足明显更常见：低血压患者中有57%（44/77）（p<0.0001）以及严重症状性缓慢性心律失常患者中有89%（8/9）（p=0.0076）在铊扫描中显示下后壁缺损。对391例连续患者测定了咖啡因水平：仅8例患者（2%）观察到水平>5mg/L，这表明当患者午夜后禁食时，甲基黄嘌呤水平足以改变对双嘧达莫的血流动力学反应并导致充血应激不理想的情况不太可能发生。
双嘧达莫诱发严重副作用的风险非常低，与在类似患者群体中进行运动试验报告的风险相当。
