Azilsartan compared to ACE inhibitors in anti-hypertensive therapy: one-year outcomes of the observational EARLY registry.

BACKGROUND: Azilsartan medoxomil (AZL-M), has been demonstrated to be more effective than the other sartans currently in use; however, there is insufficient information available comparing it with ACE-inhibitors. Therefore, we aimed to compare the efficacy, safety, and tolerability of AZL-M with that of ACE-inhibitors in a real life clinical setting. METHODS: The EARLY registry is a prospective, observational, national, multicentre registry with a follow-up period of 12 months. There were two principal objectives: 1) documentation of the achievement of target BP values set according to recent national and international guidelines, and 2) description of the safety profile of AZL-M. RESULTS: A total of 3 849 patients with essential arterial hypertension were recruited from primary care offices in Germany. Patients who initiated monotherapy at baseline comprising either AZL-M or an ACE-inhibitor were included at a ratio of seven to three. Results demonstrated that a blood pressure target of <140/90 mmHg was achieved by a significantly greater proportion of patients in the AZL-M group (61.1 %) compared with the ACE-inhibitor group (56.4 %; p < 0.05; OR, 1.21; 95 % CI, 1.03-1.42), with this finding maintained after adjusting for differences in baseline characteristics. AZL-M appeared to have an equivalent safety profile to the ACE-inhibitors, with a similar incidence of adverse events in the two patient groups (p = 0.73). CONCLUSIONS: These data add to the results of previous randomized controlled clinical trials suggesting that, compared with other agents that target the renin-angiotensin system, AZL-M provides statistically significant albeit small improvements in blood pressure control.

The renin-angiotensin receptor blocker azilsartan medoxomil compared with the angiotensin-converting enzyme inhibitor ramipril in clinical trials versus routine practice: insights from the prospective EARLY registry.

BACKGROUND: Patient characteristics and blood pressure-related outcomes in randomized clinical trials (RCTs) differ from clinical practice because of stringent selection criteria. The present study aimed to explore the relationship between clinical trials and clinical practice. We analyzed data from patients enrolled in the "Treatment with Azilsartan Compared to ACE-Inhibitors in Anti-Hypertensive Therapy" (EARLY) registry comparing blood pressure (BP) effects of the angiotensin receptor blocker (ARB) azilsartan medoxomil (AZL-M) with the angiotensin-converting enzyme (ACE) inhibitor ramipril between patients who met the eligibility criteria of a previous RCT and those who did not. METHODS: Patients with primary arterial hypertension were consecutively enrolled from primary care offices in Germany into the EARLY registry in a 7:3 ratio for treatment with AZL-M or an ACE inhibitor, provided that they met the following criteria at baseline: 1) no antihypertensive treatment prior to inclusion or a non-renin-angiotensin system (RAS) based monotherapy; 2) initiation of treatment with either AZL-M or an ACE inhibitor alone. Analyses were performed to evaluate BP effects for patients in the EARLY registry who met the selection criteria of a prior RCT (RCT+) versus those who did not (RCT-). RESULTS: Out of 3,698 patients considered, 1,644 complied with the RCT criteria (RCT+) while 2,054 did not (RCT-). RCT- patients (55.5%) displayed a higher risk profile in terms of age and comorbidities, and a wider spectrum of BP values at baseline, as highlighted by the grades of hypertension and mean BP values. The proportion of patients who achieved target blood pressure control in the RCT+ group was significantly higher for AZL-M versus ramipril (64.1 versus 56.1%; P<0.01), in accordance with the result of the clinical trial. In the RCT- AZL-M group, the proportion of patients who met BP targets was lower (58.1%) than in the RCT+ AZL-M group (64.1%), whereas the proportion of patients with target BP values in the RCT- ramipril and the RCT+ ramipril groups was similar (57.7 versus 56.1%). Thus, in contrast to results for the RCT+ group, in the RCT- group, the target BP attainment rate for AZL-M was not significantly superior to that for ramipril. However, the tolerability profile of AZL-M and ramipril was comparable in both populations. At the 12-month follow-up, death and stroke rates were low (≤0.5%) and adverse events did not differ between the AZL-M and ramipril groups, irrespective of RCT eligibility. CONCLUSIONS: These data confirm that the EARLY population comprised a broader spectrum of hypertensive patients than RCTs, and the differences in patient characteristics were accompanied by disparate rates of blood pressure goal attainment. Overall, the validity of the RCT was demonstrated and confirmed in clinical practice with a broader range of patients with various comorbidities.

Patients With Newly Diagnosed Hypertension Treated With the Renin Angiotensin Receptor Blocker Azilsartan Medoxomil vs Angiotensin-Converting Enzyme Inhibitors: The Prospective EARLY Registry.

For patients with newly diagnosed hypertension, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are usually the first-line therapies. There is, however, no real-life data regarding the relative clinical effectiveness and tolerability of either drug class. The prospective registry, Treatment With Azilsartan Compared to ACE Inhibitors in Antihypertensive Therapy (EARLY), was conducted to evaluate the effectiveness of the ARB azilsartan medoxomil (AZL-M) vs ACE inhibitors in real-world patients. Of the 1153 patients with newly diagnosed hypertension who were included in the registry, 789 were prescribed AZL-M and 364 were prescribed an ACE inhibitor. After multivariate adjustment, AZL-M was found to provide superior blood pressure reduction and better target blood pressure (<140/90 mm Hg) achievement. The proportion of patients with adverse events was not statistically different between groups. The authors conclude that in newly diagnosed hypertensive patients, AZL-M provides superior blood pressure control with a similar safety profile compared with ACE inhibitors.

Effect of myrtol standardized and other substances on the respiratory tract: ciliary beat frequency and mucociliary clearance as parameters.

INTRODUCTION: Myrtol standardized is a phytomedicine obtained by distillation, consisting of many constituents. In vitro and in vivo, the major monterpenes, d-limonene, 1,8-cineole, and alpha-pinene, are used as biological marker substances. Myrtol standardized has secretolytic, secretomotor, and mucolytic effects in addition to anti-inflammatory and antioxidative actions. The aim of the study was to investigate the effects of different concentrations of Myrtol standardized on in vivo mucociliary clearance in mice and the ciliary beat frequency (CBF) in rat tracheal rings. METHODS: Data regarding the effects of 1,8-cineole and N-acetylcysteine (NAC) were compared. Salbutamol was used as a positive control. CBF was measured using rat tracheal explants and a high-speed video camera linked to a microscope with specific software equipment. Mucociliary clearance was determined using the microdialysis technique, which measured the acceleration of a fluorescent sample in the trachea in vivo. RESULTS: Myrtol standardized accelerated both CBF and mucociliary transport in a concentration-dependent manner. Significant effects were seen at a concentration of 0.01% Myrtol regarding CBF (P<0.01) and 17.1 mg/kg body weight regarding mucociliary clearance experiments (P<0.05) according to doses relevant to humans. The 1,8-cineole dosage relative to humans only accelerated the mucociliary clearance in vivo without having an effect on the CBF. Extremely high doses of Myrtol were not able to additionally increase the CBF effect in comparison to salbutamol. Compared to NAC, also used in a dosage relative to humans, Myrtol standardized showed a tendency to be more effective. CONCLUSION: In summary, the present data suggest that Myrtol standardized is a pharmacologically important drug which, when used at a dose relative to humans, shows positive effects on both measured parameters, CBF and mucociliary clearance, in vivo.