As previously reported for all baseline rhythms 12 and 13, there were significant differences in race and hypertension history between β1389 Arg/Arg and Gly carriers groups, as well as between the 2 β1389 Gly carrier/α2c322–325 groups that were related to the β1389 Gly and α2c322–325, deletion alleles being more prevalent in blacks 11, 12, 13 and 14. There were 190 new-onset AF events in the entire 2,392 patient cohort, for an overall event rate of 7.9%. In the 925 DNA substudy patients,

there were 80 new-onset AF events (rate, 8.6%). In the entire BEST cohort, there was a lower incidence of new-onset AF in the bucindolol group than in the placebo group (n = 75 [6.2%] vs. n = 115 [9.7%] HR: 0.59 [95% CI: 0.44 to 0.79]), corresponding to a 41% risk reduction (Table 2). There was a similar decrease in the incidence of new-onset AF in the DNA substudy in the bucindolol group compared to the www.selleckchem.com/products/sch-900776.html placebo group (n = 31 [6.7%] vs. n = 49 [10.7%]; HR: 0.57 [95% CI: 0.36 to 0.90]) (Table 2). Data presented in Table 2 indicate that 85% of events were detected

from adverse event forms as opposed to routine ECGs only; thus, most of the events were symptomatic. Time to first event curves for the entire cohort and DNA substudy are given in Figure 1. Table 3 gives the reduction in new-onset AF analyzed by event duration. AF events were classified as short duration paroxysmal (<24 h), longer duration paroxysmal (between 24 h and 7 days), CAL 101 or persistent (longer than 7 days). Greater than two-thirds (67.9%) of the events were persistent AF, with 23.2% of events longer paroxysmal and only 8.9% of events being short paroxysmal. By HR, bucindolol treatment effects were similar for the 3 AF durations, with HR of 0.51 (p = 0.183), 0.57 (p = 0.066), Thiamet G and 0.62 (p = 0.007) for shorter paroxysmal, longer paroxysmal, and persistent AF, respectively (Table 3). However, event rates were low in the paroxysmal groups, and the persistent AF group was the only one that attained statistical

significance. Table 4 gives HR data by genotype group. In the 441 β1389 Arg/Arg patients, bucindolol was associated with a marked decrease in the incidence of new-onset AF (HR: 0.26 [95% CI: 0.12 to 0.57], p = 0.0003). In contrast, bucindolol had no impact on the incidence of new-onset AF in the 484 β1389 Gly carriers (HR: 1.01 [95% CI: 0.56 to 1.84], p = 0.97). In the time to first event curves shown in Figure 2, the 74% risk reduction by bucindolol in β1389 Arg/Arg patients was associated with an early divergence of curves. There was no reduction in new-onset AF in the β1389 Gly carriers who received bucindolol compared to placebo. These results yielded a significant statistical interaction (p = 0.008) between treatment and β1389 Arg/Gly genotypes. For both heart failure endpoints (12) and serious ventricular arrhythmias (13), when HFREF patients are β1389 Gly carriers, the type of associated α2c322–325 Wt/Del polymorphism can alter bucindolol treatment effects.