Combination therapy with an Xa inhibitor and antihypertensive agent improved anticoagulant activity in patients with nonvalvular atrial fibrillation: the hypertension and atrial fibrillation treated by rivaroxaban for the morning and night with sYnergy with calcium antagonists (HARMONY) study

ABSTRACT

Background: Anticoagulant activity and blood pressure increase in the morning. The aim of this study was to evaluate changes of anticoagulant activity, blood pressure and target organ damage in patients with nonvalvular atrial fibrillation (AF) given combination treatment with Xa inhibitor and antihypertensive agent.

Methods: We enrolled 72 patients with nonvalvular AF. Rivaroxaban (10–15 mg) was continuously administered once daily over 8 weeks (study period I). For subjects (n = 50) who exhibited uncontrolled morning hypertension (home systolic blood pressure [SBP]≥125 mmHg) at the end of study period I (at 8 weeks), nifedipine CR (20–40 mg) was added at bedtime, and rivaroxaban administration was continued an additional 8 weeks. We assessed prothrombin fragment 1 + 2 (optimal range: 69–229 pmol/L) and D-dimer (negative D-dimer measurement: <1.0 μg/mL).

Results: The percentage of patients with optimal-range prothrombin fragment 1 + 2 was significantly increased at 4 weeks compared to baseline (70.8% vs. 86.1%, p = .033). In period II, office and home morning SBP were reduced at 12 compared to 8 weeks (office SBP: 135.2 ± 15.7 vs. 125.6 ± 18.4mmHg, p < .001; home morning SBP: 133.5 ± 10.5 vs. 119.9 ± 12.1mmHg, p<.001).The percentage of patients with negative D-dimer  was increased at 8 weeks compared to baseline (92% vs. 100%, p = .044), and remained at 100% at 16 weeks.

Conclusions: Xa inhibitor therapy improved anticoagulant activity, and additional antihypertensive therapy maintained the anticoagulant activity in patients with nonvalvular AF.

KEYWORDS:

• Hypertension
• atrial fibrillation
• anticoagulation therapy
• blood pressure
• combination therapy

Acknowledgments

We thank all the following doctors and participants: Kazuki Sato, Heart Clinic; Kiyoshi Nishino, Nishino Medical Clinic; Masato Nishimura, Tsurumi Central Clinic, Yoshiki Hata, Minamino Heart Clinic, Yasushi Wakita, Ohkuma Hospital; Hiroaki Sugihara, Shimoda Medical center; Yuichiro Nakamura, Nakamura Cardiovascular Clinic; Naoki Nakagawa, Asakihawa Medical University; Kazuo Moroe; Moroe Clinic; Masaki Nie, Ebina General Hospital; Mitsuhiro Nishimura, Tenshi Hospital; Takeyuki Yaginuma, Nihonmatsu Hospital; Akihiro Sato, Minami-Aizu Hospital; Yasunari Muramatsu, Omotego Clinic; Shu Suzuki, Tohoku Kosai Hospital; Makiko Kohno, Owada Naika Ichouka; Tetsuro Yoshida, Onga Hospital; Hidenori Shimomura, Fukuoka Tokushukai Hospital; Toshiyuki Takahashi, Koga General Hospital; Norito Homma, Homma Hospital.