P1462IMPACT OF HEART RATE AND BETA-BLOCKER USE ON THE LONG-TERM SURVIVAL OF CHRONIC HEMODIALYSIS PATIENTS
Authors: Moromizato Takuhiro , Iseki Kunitoshi , Study Group OCTOPUS 
Published: June 2020

Abstract

Background and Aims
Increase in resting heart rate might influence mortalities of dialysis patients, and the use of β-blocker might improve their survival probability. However, the influence of heart rate and benefits of β-blocker on their survival are difficult to quantify because of following obstacles: prone to measurement errors; inherent association of heart rate with blood pressures, comorbidities, and medication use; and a necessity of repeated measurements of vital signs and medication use. Therefore, at the design process of our previous randomized control trial on the Olmesartan Clinical Trial in Okinawan patients under OKIDS (OCTOPUS), we included the repeated measures design to quantify the influence of vital sign values on the survival retrospectively. We combined the repeated measurement data and additional the long-term prognosis information of the participants obtained after the OCTOPUS with aim of investigating the influence of time varying covariates: heart rates, blood pressures, and β-blocker use, on the long-term survival of hemodialysis patients.

Method
We investigated 461 adult OCTOPUS participants who received chronic hemodialysis and antihypertensive medications in Okinawa. The OCTOPUS trial, which was conducted between June 2006 and June 2011, did not detect the survival benefit of angiotensin receptor blocker (ARB)NDT 2013, but the study and the additional follow-up of participants’ prognosis provided us with information to investigate influence of predictors on long-term survival in the population. Throughout the OCTOPUS trial, study participants were measured pre-dialysis blood pressures, pre-dialysis resting heart rates, and their medication use for one week at their dialysis centers every six months after their participations. Following the trial, we collected the prognosis information of all participants until July 31st, 2018. Finally, we merged the multiple-measured data during the OCTOPUS with the prognosis data. Mean values of three measurements of blood pressures and heart rates and β-blocker use were introduced to the Cox-regression model as time-varying covariates with essential non-time varying covariates, which include age, gender, and diabetes.

Results
In this retrospective cohort study, 221 (47.9%) out of 461 participants deceased, and the median follow-up length was 10.21 years. Initial mean resting heart rate and pre-dialysis mean blood pressure were 78(±10) per minute and 159.5(±14) mmHg, respectively. 10% of participants were prescribed β-blocker initially. The resting heart rate of all participants significantly decreased by 1.75 and 2.45 per minutes after two and four years respectively. β-blocker could significantly decrease the mean heart rate by 3.54 and 2.90 per minutes after two and four years. With our Cox-regression with the time varying covariates, increase of heart rate was significantly associated with higher mortality (P=0.002), but the use of β-blocker was not associated with the mortality. (P=0.691) Additionally, we could not detect the interaction of heart rate and β-blocker use on the mortality. (P= 0.796) Although lower blood pressure was significantly associated with higher mortality in our initial Cox-regression analysis, an introduction of interaction term of heart rate and blood pressure remove the significance of influence of blood pressure on the survival.

Conclusion
In hypertensive chronic hemodialysis patients, higher heart rate is associated with higher mortality. However, use of beta-blocker was not associated with improvement of their mortality.