Triple therapy with salmeterol/fluticasone propionate 50/250 plus tiotropium bromide improve lung function versus individual treatments in moderate-to-severe Japanese COPD patients: a randomized controlled trial - Evaluation of Airway sGaw after treatment with tripLE.

PURPOSE: Triple therapy using salmeterol/fluticasone propionate (FP) and tiotropium bromide is commonly used to treat chronic obstructive pulmonary disease (COPD), but sparse efficacy data exist in COPD patients with fewer symptoms and with a lower dose of inhaled corticosteroid in Japanese patients. The effects of of salmeterol/fluticasone propionate 50/250 µg (SFC250) twice daily plus tiotropium 18 µg (TIO) once daily and individual treatments on lung function were compared. PATIENTS AND METHODS: Fifty three Japanese COPD patients participated in this randomized, double-blind, double-dummy, Williams square design crossover study. Lung function was assessed by plethysmography and spirometry. RESULTS: The primary endpoint of postdose specific airway conductance area under the curve (AUC0-4h) on day 28 was significantly higher following SFC250 + TIO (0.854) compared with TIO (0.737, 15.8%) and SFC250 (0.663, 28.8%) alone. SFC250 + TIO significantly improved trough forced expiratory volume in 1 second from baseline versus TIO (0.161 L, P<0.001) and SFC250 (0.103 L, P=0.008). SFC250 + TIO significantly improved residual volume compared with TIO (P<0.001) and SFC250 (P=0.003) on day 28. Nonsignificant improvements were seen in trough inspiratory capacity, total lung capacity, and thoracic gas volume. There was no mean change seen in rescue medication. CONCLUSION: Triple therapy using SFC250 + TIO was well tolerated and gave a greater improvement in bronchodilation compared with TIO and SFC250 alone in Japanese patients with COPD. There was improvement in few symptoms, but no mean change was seen in patient-reported outcomes measured by rescue medication use.

Anomalous right coronary artery originating from the distal left circumflex artery: single coronary artery with choronic atrial fibrillation.

This report describes a patient with a single coronary artery in whom the right coronary artery originated from the distal left circumflex artery. Single coronary artery is a rare congenital anomaly of the coronary circulation which is often associated with other congenital cardiac malformations. This anomaly is thought to be clinically significant especially in patients with atrial fibrillation, although no other associated cardiac anomaly was detected.

Rationale for the use of combination angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker therapy in heart failure.

BACKGROUND: The present multicenter study investigated whether the combination of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) is more beneficial for preventing left ventricular remodeling and suppressing neurohumoral factors than either ACEI or ARB alone. METHODS AND RESULTS: One hundred and six patients with mild-to-moderate congestive heart failure treated in 26 Japanese institutes were randomly assigned to the combination therapy or monotherapy. Changes in physical activity (New York Heart Association functional classes, Specific Activity Scale (SAS)), concentrations of neurohumoral factors (plasma renin activity, angiotensin II, aldosterone, and brain natriuretic peptide (BNP)), and cardiac function for 6 months were compared between the 2 groups. It was found that the combination therapy, which was administered at doses standard in Japan, increased the SAS score (4.5 +/- 1.5 to 4.9 +/- 1.5, p<0.05) and decreased the plasma BNP concentration (183 +/- 163 to 135 +/- 118 pg/ml, p<0.05). In contrast, there were no changes in SAS score (4.5 +/- 1.4 to 4.6 +/- 1.4, NS) or BNP concentration (156 +/- 157 to 151 +/- 185 pg/ml, NS) in the patients receiving monotherapy. CONCLUSIONS: The results of the study demonstrate that the combination therapy, even at the standard doses for Japan, improves physical activity and plasma BNP concentration more than the monotherapy. A larger study is required to assess the effects of the combination therapy on major clinical outcomes.

Twice-daily administration of a long-acting angiotensin-converting enzyme inhibitor has greater effects on neurohumoral factors than a once-daily regimen in patients with chronic congestive heart failure.

Although many clinical trials have evaluated the use of long-acting angiotensin-converting enzyme (ACE) inhibitors in patients with chronic congestive heart failure (CHF), there are no data regarding whether a once-daily or twice-daily regimen is preferable with respect to effects on the neuroendocrine system. To address this issue, the authors evaluated the comparative effects of the administration schedule on neurohumoral factors and autonomic nervous activity in patients with CHF. Thirty-two patients with mild compensated CHF received lisinopril (5-20 mg/d) orally either once a day (n = 17) or twice a day (n = 15) for more than 3 months. After this initial therapy, patients receiving a once-daily regimen switched to a twice-daily regimen and vice-versa, and patients were followed for an additional 3 months. Neurohumoral factors and the coefficient of variance in the electrocardiographic R-R interval (CVRR) were measured. Hemodynamic parameters, renal function, plasma concentrations of brain natriuretic peptide and aldosterone, and CVRR did not differ between the two regimens. However, the plasma concentration of norepinephrine was significantly lower, and plasma renin activity tended to be lower with the twice-daily regimen. These findings suggest that twice-daily administration of long-acting ACE inhibitors may have better effects on the neuroendocrine system than a once-daily regimen in patients with mild CHF.

Analysis of transmural trends in myocardial integrated backscatter in patients with progressive systemic sclerosis.

Cardiac involvement in progressive systemic sclerosis (PSS) is common and has a strong negative impact on the prognosis, especially when autoantibodies are present. To determine whether ultrasonic tissue characterization can detect early ultrastructural changes in the sclerodermal myocardium, we analyzed the transmural heterogeneity in myocardial integrated backscatter (THIB). "A-THIB" was defined as the absolute difference in integrated backscatter between the left (subendocardial) and right (subepicardial) ventricular halves of the myocardium in the septum and posterior wall, and was measured in 11 patients with PSS and 10 age- and sex-matched healthy participants. A-THIB in patients with PSS was higher than that in healthy participants (1.3 +/- 1.3 vs 4.0 +/- 1.4 dB for the septum and 1.1 +/- 0.7 dB vs 2.8 +/- 0.4 dB for the posterior wall; mean +/- SD, respectively, P <.0005). Septal A-THIB was higher in patients with PSS with than without anti-Scl70 or antinucleolar antibodies (3.2 +/- 1.1 vs 5.0 +/- 1.0 dB, P =.0165). Early changes in the myocardium of patients with PSS, possibly related to increased interstitial collagen deposition, can be detected by quantitative analysis of THIB.