Age-Related Clinical Outcomes of Patients with Non-Valvular Atrial Fibrillation: Insights from the COOL-AF Registry

Abstract

Purpose: We aimed to compare the rate of clinical outcomes among three age groups (<65, 65-74, and ≥75 years) of adult patients with non-valvular atrial fibrillation (NVAF).

Patients and methods: We prospectively enrolled NVAF patients from 27 Thailand medical centers. The following were collected at baseline: demographic data, risk factors, comorbid conditions, laboratory data, and medications. The clinical outcomes were ischemic stroke (IS) or transient ischemic attack (TIA), major bleeding (MB), intracerebral hemorrhage (ICH), heart failure (HF), and death. All events were adjudicated. Patients were categorized according to age group into three groups; age <65, 65-74, and ≥75 years.

Results: Among the 3402 patients that were enrolled during 2014-2017, the mean age was 67.4±11.3 years, and 2073 (60.9%) were older. The average follow-up was 25.7±10.6 months. Oral anticoagulants were given in 75.4% of patients (91.1% of OAC was warfarin). The incidence rate of IS/TIA, MB, ICH, HF, and death was 1.43 (1.17-1.74), 2.11 (1.79-2.48), 0.70 (0.52-0.92), 3.03 (2.64-3.46), and 3.77 (3.33-4.24) per 100 person-years, respectively. The risk of IS/TIA, MB, ICH, HF, and death increased with age both before and after adjustment for potential confounders. Even though OAC reduced the risk of IS/TIA, it increased the risk of MB. Net clinical benefit (NCB) analysis favored oral anticoagulant (OAC) in the high-risk subset of older adults.

Conclusion: Older adult NVAF patients had a significantly increased risk of IS/TIA, MB, ICH, HF, and death compared to younger NVAF before and after adjustment for potential confounders. Strategies to reduce overall risk, including OAC use and choice and integrated care, should be implemented.

Keywords: COOL-AF registry; NVAF; Thailand; age-related clinical outcomes; non-valvular atrial fibrillation; patients.

Figure 1

Incidence rate of ischemic stroke (IS)/transient ischemic attack (TIA), major bleeding (MB), intracerebral hemorrhage (ICH), heart failure (HF), and death compared between patients aged <65, 65–74, and ≥75 years.

Figure 2

Forest plot of unadjusted and adjusted hazard ratios and their 95% confidence intervals for ischemic stroke/transient ischemic attack (TIA), major bleeding, intracerebral hemorrhage (ICH), heart failure, and death in patients aged 65–74, and ≥75 years as compared to those aged <65 years (<65 years was used as a reference).

Figure 3

Cumulative event rate for ischemic stroke/transient ischemic attack (TIA), major bleeding, intracerebral hemorrhage (ICH), and death over time compared between patients aged <65, 65–74, and ≥75 years.  A-C: unadjusted analysis. D-F: analysis adjusted for confounders.

Figure 4

Cubic spline graph of adjusted hazard ratio (blue line) and 95% confidence interval (purple shaded area) (Y-axis) relative to age (X-axis) for (A) ischemic stroke/transient ischemic attack (TIA), (B) major bleeding, (C) intracerebral hemorrhage (ICH), and (D) death.

Figure 5

Rate of ischemic stroke (IS)/transient ischemic attack (TIA), major bleeding, and intracerebral hemorrhage (ICH) according to age and oral anticoagulant (OAC) status (A), and according to age compared between warfarin and non-vitamin K antagonist oral anticoagulant (NOAC) (B). Net clinical benefit (NCB) and 95% confidence interval (CI) according to age compared between OAC and no OAC, and between NOAC and warfarin (C).