Thrombocytopenia as a Bleeding Risk Factor in Atrial Fibrillation and Coronary Artery Disease: Insights From the AFIRE Study

Abstract

Background Thrombocytopenia poses a risk of bleeding in patients with chronic coronary syndrome after coronary intervention. However, whether thrombocytopenia also increases the bleeding risk in patients with atrial fibrillation and chronic coronary syndrome remains unclear. Methods and Results This study evaluated the AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial. Thrombocytopenia was defined as platelet count <100 000/mm³ level at enrollment. Primary end points included incidence of major bleeding based on the International Society on Thrombosis and Hemostasis criterion and major adverse cardiovascular ischemic events (cardiac death, myocardial infarction, and stroke). A total of 2133 patients were classified into the thrombocytopenia (n=70) and nonthrombocytopenia (n=2063) groups. Major bleeding was significantly higher in the thrombocytopenia group than in the nonthrombocytopenia group (10.0% versus 4.1%, P=0.027). The thrombocytopenia group tended to have a higher risk of major adverse cardiovascular ischemic events (11.4% versus 6.2%, P=0.08). The bleeding incidence was significantly higher in patients with thrombocytopenia receiving combination therapy with rivaroxaban and a single antiplatelet drug (thrombocytopenia group, 14.3%, versus nonthrombocytopenia group, 5.0%; hazard ratio, 3.18 [95% CI, 1.27-7.97], P=0.014). Thrombocytopenia was an independent predictor of major bleeding (hazard ratio, 2.57 [95% CI, 1.19-5.56], P=0.017). Conclusions Among patients with atrial fibrillation and chronic coronary syndrome, thrombocytopenia was significantly associated with increased risk of major bleeding. Selecting drugs for patients with thrombocytopenia continuing antithrombotic therapy should be given special consideration. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02642419. https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000016612.

Keywords: atrial fibrillation; chronic coronary syndrome; thrombocytopenia.

Figure 1. Kaplan–Meier curves for major bleeding and MACE.

A, Kaplan–Meier estimates of survival with freedom from major bleeding with and without thrombocytopenia. B, Kaplan–Meier estimates of survival with freedom from MACE with and without thrombocytopenia. MACE indicates major adverse cardiovascular ischemic events.

Figure 2. Kaplan–Meier curves for thrombocytopenia and treatment group.

Kaplan–Meier curves for (A) major bleeding and (B) MACE (4 groups, based on the thrombocytopenia/nonthrombocytopenia group and treatment type). Combi indicates combination therapy with rivaroxaban plus antiplatelet agent; MACE, major adverse cardiovascular ischemic event; mono, monotherapy with rivaroxaban; and TP, thrombocytopenia.

Figure 3. Association between platelet counts and major bleeding (A) or MACE (B).

Restricted cubic spline curve shows the risks of major bleeding and MACE throughout the range of platelet counts. The table shows the values of hazard ratios with 95% CIs for the whole range of platelet counts at intervals of 50 000/mm³. MACE indicates major adverse cardiovascular ischemic event.