Impacts of Patient Characteristics on the Effectiv

Authors: Koichiro Kinugawa Ryozo Nagai Hiroshi Inoue Hirotsugu Atarashi Yoshihiko Seino Takeshi Yamashita Wataru Shimizu Takeshi Aiba Masafumi Kitakaze Atsuhiro Sakamoto Takanori Ikeda Yasushi Imai Takashi Daimon Katsuhiro Fujino Tetsuji Nagano Tatsuaki Okamura Masatsugu Hori The JLand Investigators

Publish Date: 2014/03/19

Volume: 31, Issue: 4, Pages: 426-439

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Abstract

Results from the multicenter trial JLand study of landiolol versus digoxin in atrial fibrillation AF and atrial flutter AFL patients with left ventricular LV dysfunction revealed that landiolol was more effective for controlling rapid HR than digoxin The subgroup analysis for patient characteristics was conducted to evaluate the impact on the efficacy and safety of landiolol compared with digoxinTwo hundred patients with AF/AFL heart rate HR ≥ 120 beats/min and LV ejection fraction LVEF 25–50 were randomized to receive either landiolol n = 93 or digoxin n = 107 Successful HR control was defined as ≥20 reduction in HR together with HR  110 beats/min at 2 h after starting intravenous administration of landiolol or digoxin The subgroup analysis for patient characteristics was to evaluate the impact on the effectiveness of landiolol in AF/AFL patients complicated with LV dysfunctionThe efficacy in patients with NYHA class III/NYHA class IV was 523/353 in landiolol and 138/91 in digoxin p  0001 and p = 0172 lower LVEF 25–35/higher LVEF 35–50 was 457/511 in landiolol and 140/127 in digoxin p  0001 and p  0001 CKD stage 1 90  eGFR/CKD stage 2 60 ≤ eGFR  90/CKD stage 3 30 ≤ eGFR  60/CKD stage 4 15 ≤ eGFR  30 was 667/591/396/667 in landiolol and 0/138/170/0 in digoxin p = 0003 p  0001 p = 0015 and p = 0040This subgroup analysis indicated that landiolol was more useful regardless of patient characteristics as compared with digoxin in AF/AFL patients complicated with LV dysfunction Particularly in patients with impaired renal function landiolol should be preferred for the purpose of acute rate control of AF/AFL tachycardiaAtrial fibrillation AF and atrial flutter AFL are common arrhythmias in patients with left ventricular LV dysfunction Over 20 of patients with heart failure exhibit AF 1 2 In these patients AF/AFL are often associated with a rapid ventricular response during the worsening of heart failure 3 4 However a sustained rapid ventricular response may further deteriorate cardiac function 5 accelerating the symptoms of heart failure 6 7 8 Intravenous administration of digoxin is considered the standard therapy for controlling the rapid ventricular response in AF/AFL patients with cardiac dysfunction or heart failure 4 9 Although digoxin has some beneficial effects for treating heart failure by way of its positive inotropic effects digoxin may also have a negative chronotropic effect as a result of vagal stimulation Of note the negative chronotropic effect develops much more slowly often taking several hours to reach the maximal effect 9 10 Shortacting parenteral βblockers can act more rapidly than digoxin and may provide a swift control of heart rate HR in these clinical settings However there is a concern that βblockers may depress cardiac function and further deteriorate ventricular dysfunction accelerating heart failure Landiolol an ultrashortacting βblocker is rapidly metabolized to inactive forms in the blood and liver resulting in a short halflife of approximately 4 min in human blood In addition it selectively binds to β1 receptors with a β1 receptor selectivity β1/β2 as high as 251 11 Based on these properties landiolol has been reported to be useful for treating several acute disorders including arrhythmias during heart surgery 12 acute myocardial infarction 13 acute decompensated heart failure 14 and refractory electrical storm 15 Ultrashortacting βblockers may be useful to control HR with minimal effects on cardiac function Even though the negative inotropic effect by landiolol is manifested it is not theoretically and practically sustained by decreasing the dose or stopping administration of these drugs

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