*For medical professionals only
“img class=”content ” sizes=”(min-width: 320px) 320px, 100vw” src=”https://mmbiz.qpic.cn/mmbiz_png/x5F5KAyDKw19I4VvcibrfNia7lD1fial5KribXqZxjxMxtoc3ichKKz6ib3w5kJias8QNRBYGn80MM0AxEgOvRLib>p>width=”6400″ >The prevalence of atrial fibrillation (AF) increases with age, and both AF and age are independent risk factors for stroke. To prevent cardiac stroke in patients with AF, clinical guidelines recommend the use of direct oral anticoagulants (DOACs), even in older patients.
Because elderly patients have more risk factors for bleeding, such as severe renal impairment, history of bleeding, previous falls, polypharmacy, and history of frailty, current elderly patients with AF have more risk factors for bleeding. Clinical evidence for the use of DOACs is still lacking.
ELDERCARE–AF study is a randomized clinical trial evaluating low-dose edoxaban (15 mg/d) in elderly patients with AF. The study found that edoxaban was superior to placebo in reducing the incidence of stroke or systemic embolism. In contrast, the edoxaban group had a higher rate of major bleeding than the placebo group; however, this difference was not statistically significant. Among the major bleeding events, the incidence of gastrointestinal bleeding was higher in the edoxaban group than in the placebo group. Although age (≤85 years and >85 years) had no effect on the efficacy of edoxaban in preventing stroke or systemic embolism, it remains unclear whether the effect of edoxaban is consistent in very elderly patients ≥90 years of age.
Recently, a study published in the journal JAMA Cardiololgy explored this issue, analyzing 1) stroke, stroke, Risk of systemic embolism or major bleeding; 2) The efficacy difference between edoxaban 15 mg and placebo in three age groups of elderly AF patients, let’s take a look.
Methods
ELDERCARE–AF was a multicenter, double-blind, Randomized, placebo-controlled, event-driven Phase III clinical study, conducted from August 5, 2016 to December 27, 2019.
Age ≥80 years old and AF patients who did not meet the standard taking conditions of DOACs were included in the study.
The reasons why these patients cannot take standard doses of DOACs include:
low creatinine clearance (<30 mL/min) , low body weight (≤45 kg),
history of vital organ hemorrhage,
continuous use of NSAIDs
concurrent use of antiplatelet drugs.
All patients enrolled in the study were from 164 hospitals in Japan and were randomly assigned in a 1:1 ratio to edoxaban (15 mg once daily) or placebo group.
Results
A total of 984 patients were included in the final analysis,
354 (36.0%) in the 80-84 age group,
374 (38.0%) in the 85-89 age group,
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256 people (26.0%) in the ≥90-year-old group.
The average age of each group:
82.2 (1.4) years old in the 80-84 year old group, < /p>
86.8 (1.4) years old in the 85-89 year old group, 92.3 (2.1) years old in the
≥90 year old group.
419 males (42.6%) and 565 females (57.4%).
The prevalence of congestive heart failure, severe renal impairment, and frailty increases significantly with age.
In the placebo group,
181 cases 10 of 80-84 years (estimated event rate 3.9% [1.2%]/patient-year),
184 of 85-89 years 18 (7.3% [1.7%]/patient-year),
16 of 127 patients ≥90 years old (10.1% [2.5%]/patient-year) A stroke or systemic embolic event occurred.
The incidence of stroke or embolism increased with age, but was not statistically different after adjustment for baseline characteristics.
In the Edoxaban group,
173 4 of 80-84 years (1.6% [0.8%]/patient-year),
7 of 190 85-89 years ( 2.8% [1.1%]/patient-year),
4 of 129 patients ≥90 years (2.4% [1.2%]/patient-year) had a stroke or Systemic embolic events.
Compared with placebo, the edoxaban group had a lower incidence rate, and was not related to age. Interaction
(80-84 years: HR 0.41, 95%CI 0.13-1.31, P=0.13;
85-89 years old: HR 0.42, 95%CI 0.17-0.99, P=0.05;
≥90 years old: HR 0.23, 95%CI 0.08-0.68, P=0.008 ; interaction P=0.65).
span>
In the placebo group,
1 in 180 patients aged 80-84 years (0.4%/patient-year) ),
7 of 183 patients aged 85-89 years (3%/patient-year),
Major bleeding events occurred in 3 of 127 patients ≥90 years (2.7%/patient-year);
In the edoxaban group,
5 of 173 patients aged 80-84 years (2.2%/patient-year),
< p>5 of 190 patients aged 85-89 years (2.2%/patient-year),
10 of 129 patients ≥90 years old (6.5%/patient-year) major bleeding events occurred.
There was no interaction between the incidence of major bleeding and age
(80-84 years: HR 5.27, 95%CI 0.61- 45.36, P=0.13;
age 85-89: HR 0.74, 95%CI 0.24-2.33, P=0.61;
≥90 years: HR 3.02, 95%CI 0.82-11.21, P=0.10; P=0.15 for interaction).
In the 80-84-year-old group of major bleeding events,
The incidence of gastrointestinal bleeding in the placebo and edoxaban groups were:
0/180 (0%/patient-year) and 3/173, respectively (1.3%/patient-year);
In the 85-89 age group, the incidences of gastrointestinal bleeding were:
4/183 (1.7%/patient-year) and 2/190 (0.9%/patient-year);
In the ≥90-year-old group, gastric The incidence of intestinal bleeding was:
1/27 (0.7%/patient-year) and 9/129 (5.9%/patient-year) (HR 8.37, 95 %CI 1.04-67.07; P=0.05).
In both placebo and edoxaban groups, all-cause mortality increased with age,
and there were no significant group differences between the edoxaban and placebo groups in all age groups
(80- 84 years old: HR 1.28, 95%CI 0.62-2.67, P=0.50;
85-89 years old: HR 0.91, 95%CI 0.53-1.53, P=0.71;
≥90 years old, HR 0.86, 95%CI 0.49-1.51, P=0.60; P=0.65 for interaction).
The composite endpoint of major bleeding or clinically relevant nonmajor bleeding in the edoxaban group:
(80-84 years: HR 1.64, 95%CI 0.90-2.97, P=0.10;
85-89 years: HR 1.63, 95 %CI 0.96-2.77; P=0.07;
≥90 years: HR 1.57, 95%CI 0.93-2.67, P=0.09; interaction P>0.99) span>
or incidence of clinically relevant nonmajor bleeding
(80-84 years: HR 1.47, 95%CI 0.79-2.74, P =0.23;
85-89 years: HR 2.00, 95%CI 1.10-3.64, P=0.02;
≥90 years old: HR 1.35, 95%CI 0.75-2.41, P=0.32; interaction P=0.64) were higher than those in the placebo group, and there was no interaction with age.
In addition, there was no interaction of age with the incidence of minor bleeding and all bleeding between the placebo and edoxaban groups;
There were no fatal hemorrhages in the edoxaban group.
Conclusions
In a subgroup analysis of the ELDERCARE-AF randomized clinical trial FINDINGS:
In Japanese AF patients ≥80 years of age, edoxaban 15 mg once daily was effective in preventing all three age groups ( superior to placebo in stroke or systemic embolism, including very elderly patients ≥90 years of age.
Compared with placebo, no major bleeding occurred with edoxaban. Statistical significance.
Source:
< span>Effect of 15-mg Edoxaban on Clinical Outcomes in 3 Age Strata in Older Patients With Atrial Fibrillation: A Prespecified Subanalysis of the ELDERCARE-AF Randomized Clinical Trial. JAMA Cardiol. 2022 Apr 13;e220480. doi: 10.1001/jamacardio.2022.0480
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