The efficacy and safety of ivabradine hydrochloride in hemodialysis patients with chronic heart failure.

INTRODUCTION: There is little evidence for ivabradine hydrochloride in patients undergoing hemodialysis. METHODS: In this open-label prospective interventional trial of hemodialysis patients with chronic heart failure, during 12 weeks of treatment, changes in Heart rate (HR), frequency of dialysis-related hypotension were examined, and we investigated health-related quality of life (HR-QOL) and adverse effects. RESULTS: 18 patients from 6 facilities were enrolled in the study. HR significantly decreased over time, from 87 ± 12.61/min at baseline to 75.85 ± 8.91/min (p = 0.0003), and systolic blood pressure also increased significantly (p < 0.0001). The frequency of dialysis-related hypotension was markedly reduced (p = 0.0001). The HR-QOL survey showed significant improvements in Social Functioning among others (p = 0.0178). No specific adverse events occurred. CONCLUSION: Ivabradine hydrochloride improved dialysis-related hypotension. Furthermore, the HR-QOL improvement effect were suggested. These results demonstrated the safety and effectiveness of ivabradine hydrochloride.

Clinical Significance of Increased Cardiac Troponin T in Patients with Chronic Hemodialysis and Cardiovascular Disease: Comparison to B-Type Natriuretic Peptide and A-Type Natriuretic Peptide Increase.

BACKGROUND: An increased cardiac troponin T (cTnT) level identifies a high-risk group in patients with end-stage renal disease; however, the mechanism of cTnT elevation remains unclear in such patients without acute coronary syndrome (ACS). Therefore, we explored the relationship between cTnT levels and the hemodynamic parameters and the prognostic potential of cTnT in stable patients with chronic hemodialysis (HD). METHODS: We included consecutive 174 patients with HD who were referred for coronary angiography due to stable coronary artery disease (CAD), peripheral artery disease (PAD), or heart failure (HF). Hemodynamic measurement was performed, and plasma cTnT, B-type natriuretic peptide (BNP), and A-type natriuretic peptide (ANP) were measured at the same time. The potential of 3 biomarkers to predict all-cause mortality, cardiac death or hospitalized HF, and vascular event was assessed. RESULTS: Increased log cTnT levels were correlated with increased log BNP and log ANP levels (r = 0.531, p < 0.001 and r = 0.411, p < 0.001, respectively). Not increased log cTnT, but increased log BNP and log ANP were associated with the presence of CAD and the extent of CAD. In contrast, they were all associated with the New York Heart Association functional classification and the presence of PAD and significantly correlated with left ventricular end-diastolic pressure (LVEDP) in an independent manner. Increased cTnT and BNP levels were associated with the mortality and hospitalized HF. However, increased cTnT was not associated with vascular events, unlike increased BNP. CONCLUSIONS: In patients with chronic HD without ACS, increased cTnT reflected increased LVEDP and the presence of HF or PAD independently, and it did not reflect the presence of CAD in contrast to increased BNP. cTnT and BNP were significant prognostic predictors; however, increased cTnT was associated with HF-related events, not with arteriosclerotic events.

The effects of increasing calcium channel blocker dose vs. adding a diuretic to treatment regimens for patients with uncontrolled hypertension.

In patients with insufficient blood pressure (BP) control, despite using a combination regimen containing an angiotensin receptor blocker and a calcium channel blocker (CCB), whether a greater dose of CCB or adding a diuretic is more effective at lowering BP remains unclear. We conducted a multicenter randomized clinical trial to compare the efficacy of switching from the daily administration of a single-pill fixed-dose combination of irbesartan (100 mg) and amlodipine (5 mg) to irbesartan (100 mg) with an increased dose of amlodipine (10 mg) (HD group, n=62) or irbesartan (100 mg) and amlodipine (5 mg) with 1 mg of indapamide (D group, n=63) in patients with poorly controlled hypertension. BP measured at home was monitored by a physician using a telemonitoring system. Between the HD and D groups, no significant differences were observed in morning home BP changes (mean reduction of systolic/diastolic BP, 1.7/0.9 mmHg; 95% confidence intervals, -2.4 to 5.7/-1.4 to 3.2; P=0.19/0.37), achievement rate of target BP (45.2% vs. 42.9%, P=0.80), BP variability independent of the mean (P⩾0.74), other variability indices (P⩾0.55) and time to stabilization, which was calculated using a fitted analysis (13.1 days vs. 11.4 days, P=0.99). Although a significant increase in serum uric acid was observed in the D group (P<0.0001), neither clinically relevant abnormal laboratory test results nor critical BP changes were observed throughout the trial period. Both antihypertensive drug combination strategies were effective treatment options. Further investigation is required to determine the appropriate use of both therapies based on the various pathologies associated with hypertension.

Amlodipine suppressed cardiac gene expression of brain natriuretic peptide, transforming growth factor-ß1 and fibronectin mediated by aldosterone in male stroke-prone spontaneously hypertensive rats.

OBJECTIVES: Amlodipine, a calcium channel blocker (CCB), is one of the most common antihypertensive medicines in Japan. We evaluated whether the calcium channel blocker confers cardiac protection through the renin-angiotensin-aldosterone system in male stroke-prone spontaneously hypertensive rats (SHR-SP). METHODS: Fifteen week-old rats were divided into 2 groups: amlodipine group (3 mg/kg/day, n = 5) and control group (n = 5). KEY FINDINGS: The CCB lowered systolic blood pressure significantly (P < 0.05). Plasma aldosterone concentration in the amlodipine group was remarkably lower than in the control group (P < 0.05), but plasma renin activity and plasma angiotensin II concentration were not different between the two groups. The CCB also suppressed the mRNA expression of brain natriuretic peptide, transforming growth factor-ß1, and fibronectin extracted from the left ventricle. CONCLUSIONS: These results suggest that amlodipine attenuates cardiac damage by lowering plasma aldosterone concentration in hypertensive rats with developing arteriosclerosis.

Renoprotective effect and cost-effectiveness of using benidipine, a calcium channel blocker, to lower the dose of angiotensin receptor blocker in hypertensive patients with albuminuria.

In hypertensive patients with chronic renal disease, angiotensin receptor blockers (ARBs) are among the first-line drugs, and calcium channel blockers (CCBs) are recommended as a second line. We examined the effects of two therapeutic strategies using ARBs and benidipine, a CCB, on blood pressure (BP), urinary albumin excretion (UAE), and cost-effectiveness in hypertensive patients with albuminuria. Patients whose BP was 140/90 mmHg or higher despite treatment with low- or medium-dose ARBs were assigned randomly to two groups. In Group A (n=14), the ARB dose was maximized and then benidipine was added until BP targets were reached (<130/85 mmHg). In Group B (n=18), benidipine was administered first and then the ARB dose was increased until BP targets were reached. The BP targets were achieved by ARB alone in 36% of Group A patients and by the addition of benidipine in 83% of Group B patients. Finally, BP decreased in each group, reaching the targets in 93% of Group A patients and 94% of Group B patients after a 4-month therapeutic period. UAE was decreased in both groups after a 4-month therapeutic period compared to the allocation period (-33+/-6% in Group A, -31+/-6% in Group B; p<0.001, respectively). The monthly drug cost was higher (11,426+/-880 vs. 8,955+/-410 yen, p=0.012) and the cost-effectiveness of antihypertensive treatment was lower (p=0.003) in Group A than in Group B. We conclude that the addition of benidipine to low- or medium-dose ARB is, in light of the renal protection and the cost-effectiveness of this approach, a useful therapeutic strategy for controlling BP in hypertensive patients with albuminuria.