Rimoldi Stefano F, Messerli Franz H, Cerny David, Gloekler Steffen, Traupe Tobias, Laurent Stéphane, Seiler Christian
From the Department of Cardiology and Clinical Research, Inselspital, University of Bern Hospital, Bern, Switzerland (S.F.R., F.H.M., D.C., S.G., T.T., C.S.); and Department of Pharmacology, European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Inserm UMR 970, University Paris Descartes, Paris, France (S.L.).
Hypertension. 2016 Jun;67(6):1205-10. doi: 10.1161/HYPERTENSIONAHA.116.07250. Epub 2016 Apr 18.
Heart rate (HR) lowering by β-blockade was shown to be beneficial after myocardial infarction. In contrast, HR lowering with ivabradine was found to confer no benefits in 2 prospective randomized trials in patients with coronary artery disease. We hypothesized that this inefficacy could be in part related to ivabradine's effect on central (aortic) pressure. Our study included 46 patients with chronic stable coronary artery disease who were randomly allocated to placebo (n=23) or ivabradine (n=23) in a single-blinded fashion for 6 months. Concomitant baseline medication was continued unchanged throughout the study except for β-blockers, which were stopped during the study period. Central blood pressure and stroke volume were measured directly by left heart catheterization at baseline and after 6 months. For the determination of resting HR at baseline and at follow-up, 24-hour ECG monitoring was performed. Patients on ivabradine showed an increase of 11 mm Hg in central systolic pressure from 129±22 mm Hg to 140±26 mm Hg (P=0.02) and in stroke volume by 86±21.8 to 107.2±30.0 mL (P=0.002). In the placebo group, central systolic pressure and stroke volume remained unchanged. Estimates of myocardial oxygen consumption (HR×systolic pressure and time-tension index) remained unchanged with ivabradine.The decrease in HR from baseline to follow-up correlated with the concomitant increase in central systolic pressure (r=-0.41, P=0.009) and in stroke volume (r=-0.61, P<0.001). In conclusion, the decrease in HR with ivabradine was associated with an increase in central systolic pressure, which may have antagonized possible benefits of HR lowering in coronary artery disease patients. CLINICAL TRIALSURL: http://www.clinicaltrials.gov. Unique identifier NCT01039389.
心肌梗死后，β受体阻滞剂降低心率（HR）显示有益。相比之下，在两项针对冠心病患者的前瞻性随机试验中，发现伊伐布雷定降低心率并无益处。我们推测，这种无效可能部分与伊伐布雷定对中心（主动脉）压的影响有关。我们的研究纳入了46例慢性稳定型冠心病患者，他们以单盲方式被随机分配至安慰剂组（n = 23）或伊伐布雷定组（n = 23），为期6个月。除β受体阻滞剂在研究期间停用外，整个研究过程中伴随的基线用药保持不变。在基线和6个月后通过左心导管直接测量中心血压和每搏输出量。为了测定基线和随访时的静息心率，进行了24小时心电图监测。服用伊伐布雷定的患者中心收缩压从129±22 mmHg升高至140±26 mmHg（P = 0.02），升高了11 mmHg，每搏输出量从86±21.8 mL增加至107.2±30.0 mL（P = 0.002）。在安慰剂组，中心收缩压和每搏输出量保持不变。伊伐布雷定使心肌耗氧量估计值（心率×收缩压和时间 - 张力指数）保持不变。从基线到随访心率的降低与中心收缩压的伴随升高（r = -0.41，P = 0.009）和每搏输出量的升高（r = -0.61，P < 0.001）相关。总之，伊伐布雷定降低心率与中心收缩压升高有关，这可能抵消了冠心病患者降低心率可能带来的益处。临床试验网址：http://www.clinicaltrials.gov。唯一标识符NCT01039389。
