on behalf of the J-RHYTHM Registry Investigators* Background--To clarify the influence of hypertension and blood pressure (BP) control on thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J-RHYTHM Registry was performed.

Background Blood pressure (BP) variability has reportedly been a risk factor for various clinical events. To clarify the influence of BP visit‐to‐visit variability on adverse events in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐RHYTHM Registry was performed. Methods and Results Of 7406 outpatients with nonvalvular atrial fibrillation from 158 institutions, 7226 (age, 69.7±9.9 years; men, 70.7%), in whom BP was measured 4 times or more (14.6±5.0 times) during the 2‐year follow‐up period or until occurrence of an event, constituted the study group. SD and coefficient of variation of BP values were calculated as BP variability. Thromboembolism, major hemorrhage, and all‐cause death occurred in 110 (1.5%), 121 (1.7%), and 168 (2.3%) patients, respectively. When patients were divided into quartiles of systolic BP‐SD (<8.20, 8.20–10.49, 10.50–13.19, and ≥13.20 mm Hg), hazard ratios (HRs) for all adverse events were significantly high in the highest quartile compared with the lowest quartile (HR, 2.00, 95% CI, 1.15–3.49, P =0.015 for thromboembolism; HR, 2.60, 95% CI, 1.36–4.97, P =0.004 for major hemorrhage; and HR, 1.85, 95% CI, 1.11–3.07, P =0.018 for all‐cause death) after adjusting for components of the CHA 2 DS 2 ‐VASc score, warfarin and antiplatelet use, atrial fibrillation type, BP measurement times, and others. These findings were consistent when BP‐coefficient of variation was used instead of BP‐SD. Conclusions Systolic BP visit‐to‐visit variability was significantly associated with all adverse events in patients with nonvalvular atrial fibrillation. Further studies are needed to clarify the causality between BP variability and adverse outcomes in patients with nonvalvular atrial fibrillation. Registration URL: https://www.umin.ac.jp/ctr/ ; Unique Identifier: UMIN000001569.

Among the angiotensin II receptor blockers (ARBs), losartan (LOS) has uricosuric action. The clinical benefits of LOS compared with those of other ARBs may be apparent when it is combined with diuretics, which have an unfavorable influence on serum uric acid (SUA). The effects of switching from combinations of ARBs other than LOS and thiazides to a fixed-dose combination comprising 50 mg LOS and 12.5 mg hydrochlorothiazide on blood pressure (BP), SUA, percent fractional excretion of UA (FEUA), and urine pH were assessed in 57 hypertensive outpatients. A significant reduction in BP was observed after 6 months (P < .01). The switching therapy significantly decreased SUA level (6.0 ± 1.3 vs. 5.7 ± 1.3 mg/dL, P < .01), which was accompanied by increases in FEUA (P < .01) and urine pH (P < .01). The change in SUA was negatively correlated with the changes in FEUA (P < .004) and estimated glomerular filtration rate (P < .05). The change in FEUA was positively correlated with the changes in urine pH (P < .05) but not with BP or estimated glomerular filtration rate. In a separate group of patients treated with ARBs other than LOS (n = 82), a significant BP reduction was observed, but no change in SUA or FEUA was observed. In conclusion, switching therapy decreased SUA level, which was accompanied by an increase in FEUA. This result may depend on the balance between LOS-induced inhibitory action of urate transporter 1 and hydrochlorothiazide-induced plasma volume reduction. The increase in urine pH plays a role in UA urinary excretion.

The efficacy and tolerability of switching therapy from free combinations of angiotensin II receptor blocker (ARB) and thiazide (A/T) to a fixed-dose of losartan and hydrochlorothiazide (L/H) has not been evaluated in Japan. We examined effects of switching therapy from variable-dose multiple-pill A/T to a fixed-dose L/H on blood pressure (BP) along with medication adherence and the degree of satisfaction in 91 hypertensive outpatients (mean age, 65.2 ± 9.6 years). After 6 months, a significant BP reduction (132 ± 9/76 ± 10 vs. 126 ± 12/72 ± 11 mm Hg), along with an improvement of attaining target BP (44.0 vs. 61.5%) and that of adherence, were observed. The magnitude of BP reduction in the participants increased their degree of satisfaction more significantly than in the participants who worsened their degree of satisfaction. The estimated glomerular filtration rate and the serum uric acid (UA) level decreased slightly but significantly. The hemoglobin A1c of participants with diabetes mellitus increased slightly but significantly. In conclusion, a switch in therapy from variable-dose, multiple-pill A/T combinations to a fixed-dose, single-pill L/H was effective in decreasing BP and serum UA in Japanese clinical practice. Metabolic side effects of L/H in patients with diabetes mellitus remain to be investigated.

No abstract