RESULTS
A total of 312 patients were included, 150 from the control group and
162 from the intervention group (Fig 1). 13 patients presented protocol
violation in the intervention group. Likewise, 13 patients were lost
during follow-up in the control group and 3 in the intervention group,
leaving a total of 137 patients in the control group and 146 in the
intervention group, in the per protocol analysis. Table 1 shows the
baseline characteristics of the participants.
Table 2 shows the main results in the control and intervention groups.
The overall mortality at 90 days, 180 days and 1 year per protocol was 8
(2.57%), 10 (3.22%) and 14 (4.50%), respectively. There were no
significant differences in mortality after one year between both groups,
both unadjusted and when adjusted for the Charlson comorbidity index
(ITT: adjusted OR 0.89, 95% CI 0.30-2.69, p=0.84; PP: OR adjusted 1.04,
95% CI 0.33-3.26, p=0.94). The rate of new admissions per year in the
control group was 27.01% while it was 25.52% in the intervention
group, p = 0.84. The same analysis was performed for each of the
hospitals without showing any significant differences. Fig 2a and 2b
show the analysis of 1-year survival by intention to treat (Hazard ratio
(95% CI) =0.91 (0.32, 2.61), p=0.87), and per protocol (Hazard ratio
(95% CI) =1.08 (0.36, 3.22), p =0.89), respectively, with no
significant differences detected in either case. On the other hand, 16
(10.74%) cardiovascular events per year were observed in the control
group and 23 (14.38%) in the intervention group (adjusted OR 1.40, 95%
CI 0.71-2.77, p value=0.33) in the per protocol analysis (Table 2).
A sample was obtained for biomarker analysis from 65 patients in the
control group and 81 in the intervention group, all from one of the
hospitals. The biomarker levels at admission, day 5, and day 30 as well
as the difference from day 5 to day 30 are shown in Table 3. In the per
protocol analysis, after adjusting for the value at day 5, no
significant differences were observed between the control and
intervention groups with respect to the difference in proadrenomedullin
levels from day 5 to day 30 (p=0.52). Neither were significant
differences detected for the PCR (p=0.2910) or in the PCT (p=0.44).
Last, the effect of change over time in biomarker values on the rate of
cardiovascular events at follow-up was assessed (Table 4). 22
cardiovascular events were observed in this patient sample. Changes in
proADM values from day 5 to day 30 showed an OR of 1.11 (95% CI: 0.09,
13.65) () of having any cardiovascular event, adjusted for its value on
day 5 and by the Charlson index (p=0.94). The same analysis was
performed taking into account the control and intervention groups, and
again no significant effect was detected for cardiovascular events at 1
year in either the control or intervention group (proADM difference:
p=0.79 and p=0.86, respectively; PCR difference: p=0.38 and p=0.20,
respectively; and PCT difference: p=0.94 and p=0.63, respectively).