Drugs or investigational compounds Effects Preclinical studies Clinical studies Improvement of current antiarrhythmic agents Azimilide (FDA approval) primarily IKr and IKs blocker but additionally blocks ICaL and INa (multi-channel blocker) several in vitro and in vivo animal models [38,39,40,41] ALIVE, A-STAR, A-COMET I and II Studies [42,43] HMR-1556 highly selective IKs blocker several in vitro and in vivo animal models [44,45] not AZD7009 primarily IKr and INa blocker, but additionally blocks Ito, IKur and IKs (multi-channel blocker) several in vitro and in vivo animal models [46,47,48] small centre clinical trial [49,50] Dronedarone (FDA approval) amiodarone like multichannel blocker (INa, ICa, IKr blocker) several in vitro and in vivo animal models [51,52,53] ADONIS,  ATHENA, EURIDIS etc. [54,55,56,57,58] Tedisamil multichannel blocker (INa, Ito, IKr, IKs, IKATP,  blocker) several in vitro and in vivo animal models [60,61,62] small centre clinical trial [63,64] Atrial selective therapeutic agents AVE0118 primarily IKur, Ito and IK,ACh blocker several in vitro and in vivo animal models [67,68,69,70,71,72] not XEN-D0101 highly selective IKur blocker several in vitro and in vivo animal models [73,74] small centre clinical trial [75] DP01 highly selective IKur blocker several in vitro and in vivo animal models [76,77] not Vernakalant primarily IKr and INa blocker, but additionally blocks Ito, INa, IKr and IKs (multichannel blocker) several in vitro and in vivo animal models [78,79,80] AVRO [81,82] Ranolazine (FDA approval) primarily INaf and INaL, and IKr blocker, but additionally blocks ICaL and IKs (multichannel blocker) several in vitro and in vivo animal models [85,86,87,88] MERLIN-TIMI [89] NIP-142, NIP-152 highly selective IK,ACh blockers several in vitro and in vivo animal models [93,94] not tertiapin Q highly selective IK,ACh blocker several in vitro and in vivo animal models [9,90,96,97] not NCX modulators KB-R7943 initially developed as selective NCX blocker, but additionally blocks Ito, IK, IK1, INa, and ICaL several in vitro and in vivo animal models not SEA-0400 selective NCX blocker, but additionally blocks ICaL several in vitro and in vivo animal models not ORM-10103 highly selective and potent NCX blocker in vitro animal model [104] not Gap-junction therapy Rotigaptide selective gap junction closer peptide several in vitro and in vivo animal models [108,109] not GAP-134 selective gap junction closer peptide several in vitro and in vivo animal models [110,111] not

Table 1: New drugs and investigational compounds developed for treating AF.