Which anticoagulation intensity works best for Asians with mitral stenosis?

The standard intensity for anticoagulation is enough to protect adult southeast Asians with moderate-to-severe rheumatic mitral stenosis (MS) against thromboembolism, with an acceptable risk of major bleeding, according to a study. 

High-intensity anticoagulation also prevents thromboembolism but with more major bleeding.

“The standard anticoagulation intensity is an optimal range for Asian population with moderate-to-severe rheumatic MS,” the researchers said.

A total of 933 patients (mean age 56.1 years) were included, with a mean follow-up of 3.8 years and 23,700 international normalized ratio (INR) values. During follow-up, 149 thromboembolic events (4.2 per 100 patient-years) and 132 major bleeding events (3.7 per 100 patient-years) occurred. [Br J Clin Pharmacol 2025;91:2273-2282]

An INR of 2.50–2.99 showed the lowest net adverse clinical events (NACE), with no significant difference between INR 2.00–2.49 and 3.00–3.50. NACE were similar (incidence rate ratio [IRR], 0.99, 95 percent confidence interval [CI], 0.66–1.54; p=0.99) between standard (2.0–3.0) and high-intensity INR (2.5–3.5).

However, standard INR resulted in a higher incidence of thromboembolism compared with high-intensity INR (IRR, 2.49, 95 percent CI, 1.13–6.23; p=0.013), but major bleeding was lower (IRR, 0.57, 95 percent CI, 0.35–0.98; p=0.045).

Intracranial haemorrhage rates did not significantly differ between the two INR intensities.

“In terms of anticoagulation intensity, our study lends support to the standard intensity INR (2.0–3.0) recommended by international guidelines, which provides protection against thromboembolism while minimizing the risk of major bleeding,” the researchers said. [Circulation 2021;143:e72-e227; Chest 2018;154:1121-1201; Eur Heart J 2021;42:373-498]

Two previous studies also suggested an INR target range of 2.0–3.0, which was confirmed by the results of the present study. [Thromb Haemost 2003;89:760-764; J Med Assoc Thai 2019;102:904-910]

High intensity

In subgroup analysis, patients aged <65 years and those with coexisting atrial fibrillation (AF) appeared to derive benefits from high-intensity INR.

“Since the risk of thromboembolism in valvular AF is known to be higher than nonvalvular AF, higher intensity INR seems like a logical approach in these high-risk patients,” the researchers said. “At the other end of the spectrum, based on the results of our study, high-intensity INR should not be used in patients who have a prior history of bleeding.”

Regardless of the INR target selected, maintaining time in therapeutic range of >65 percent is necessary for warfarin to effectively protect against stroke while minimizing the risk of bleeding. [Chest 2018;154:1121-1201]

“In rural or remote areas, various strategies should be implemented to ensure close monitoring, such as using a portable INR device, which can be performed locally with remote guidance by experienced clinicians,” the researchers said.

Participants

The current multicentre, retrospective study examined patients with MS who had not undergone valve replacement or repair and required long-term warfarin therapy at two hospitals in Thailand from 2013 to 2018. Thromboembolism and major bleeding were the primary outcomes. Researchers then compared the IRRs for these events at each level of anticoagulation intensity.

“Moderate-to-severe MS patients living in low-to-middle-income countries often have poorer outcomes compared to high-income countries due to limited access or prolonged waiting time for corrective surgery,” according to the researchers. [Circulation 2014;129:1568-1576]

Moreover, “these patients commonly suffer from AF induced by valve diseases. Coexistence of AF and MS places these patients at very high risk of stroke and systemic embolism,” they added.