title: 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.
abstract: 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.
authors.affiliation: Institut für Pharmakologie und präventive Medizin, Menzelstrasse 21, 15831, Mahlow, Germany. peter.bramlage@ippmed.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Bramlage
authors.affiliation: Universitätsklinikum Erlangen, Medizinische Klinik 4, Schwerpunkt Nephrologie/Hypertensiologie, Erlangen, Germany. roland.schmieder@uk-erlangen.de.
authors.forename: Roland E
authors.initials: RE
authors.lastname: Schmieder
authors.affiliation: Institut für Herzinfarktforschung GmbH, Ludwigshafen, Germany. gitta@klilu.de.|Herzzentrum Ludwigshafen, Medizinische Klinik B, Ludwigshafen, Germany. gitta@klilu.de.
authors.forename: Anselm K
authors.initials: AK
authors.lastname: Gitt
authors.affiliation: Clemens-Hospital Münster, Klinik für Innere Medizin I, Münster, Germany. p.baumgart@clemenshospital.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Baumgart
authors.affiliation: Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany. felix.mahfoud@uniklinikum-saarland.de.
authors.forename: Felix
authors.initials: F
authors.lastname: Mahfoud
authors.affiliation: MedCommTools, Medical-Scientific Consultancy, Hannover, Germany. dr.buhck@medcommtools.de.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Buhck
authors.affiliation: Institut für Herzinfarktforschung GmbH, Ludwigshafen, Germany. ouarrak@ihf.de.
authors.forename: Taoufik
authors.initials: T
authors.lastname: Ouarrak
authors.affiliation: Takeda Pharma, Berlin, Deutschland. martina.ehmen@takeda.de.
authors.forename: Martina
authors.initials: M
authors.lastname: Ehmen
authors.affiliation: Universitätsklinikum Düsseldorf, Klinik für Nephrologie, Düsseldorf, Germany. sebastian.potthoff@med.uni-duesseldorf.de.
authors.forename: Sebastian A
authors.initials: SA
authors.lastname: Potthoff
mesh_terms: D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D062186:Arterial Pressure / Q000187:drug effects*; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D015897:Comorbidity; D005260:Female; D005858:Germany; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010069:Oxadiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D018579:Patient Selection; D017410:Practice Guidelines as Topic; D011320:Primary Health Care / Q000592:standards; D011446:Prospective Studies; D017257:Ramipril / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000592:standards; D012042:Registries; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012107:Research Design; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D010069:Oxadiazoles; D017257:Ramipril; C557413:azilsartan medoxomil