Optimal international normalized ratio (INR) in secondary prevention of stroke in non-valvular atrial fibrillation.
[Purpose] In order to elucidate optimal international normalized ratio (INR) for secondary prevention of stroke in nonvalvular atrial fibrillation (NVAF), we evaluated risk of severe recurrent ischemic stroke and major hemorrhagic complications according to patients’ age and INR. [Methods] We analyzed data of two prospective studies, Japanese Nonvalvular Atrial Fibrillation-Embolism Secondary Prevention Cooperative Study (Stroke 2000; 31: 817) and NCVC NVAF Secondary Prevention Study to elucidate relationships of major ischemic stroke and hemorrhage with INR. In both studies, all patients with cardioembolic stroke were given warfarin, monitored with INR every month, and followed up for primary endpoints of ischemic stroke and embolism to other part of the body, and for secondary endpoints of major hemorrhagic complications. There were 206 patients enrolled in total (154 men and 52 women). We divided them into two groups, elderly group aged 70 years or more (n=109, median INR 1.6–1.8) and non-elderly group aged less than 70 years (n=97, median INR 1.8–2.0). We calculated annual occurrence rate of major stroke (NIH stroke scale score >= 10) and severe hemorrhagic complications in the two groups. [Results] During the mean follow-up period of 548 days, major stroke was seen in 4 patients with INR<1.6 only in the elderly group (INR=0.95, 1.28, 1.54, 1.57; 13.3%/y in INR<1.6), but in none in the non-elderly group (p=0.0475, Fisher’s exact test between the two groups). In the elderly group, severe hemorrhagic complications occurred in none with INR<2.2 (0%/y), in 5 patients with INR between 2.2 and 3.0 (INR=2.25, 2.59, 2.66, 2.80, 2.98, 17.3%/y), and 2 with INR>=3.0 (INR=3.05, 3.13; 38.4%/y). They occurred in none with INR<3.0 (0%/y) and in 1 with INR>3.0 (INR=3.55, 16.4%/y) in the non-elderly group (p=0.0275 v.s. the elderly group). [Conclusions] Both major ischemic stroke and hemorrhage occur more frequently in the elderly than in the non-elderly. In the elderly group, INR between 1.6 and 2.2 seems optimal to prevent both major stroke and hemorrhage, while INR below 3.0 is desired in the non-elderly group to avoid hemorrhagic complications.