title: Efficacy and safety of two dosages of canrenone as add-on therapy in hypertensive patients taking ace-inhibitors or angiotensin II receptor blockers and hydrochlorothiazide at maximum dosage in a randomized clinical trial: The ESCAPE-IT trial.
abstract: OBJECTIVE
  To evaluate the effects of canrenone as add-on therapy in patients already treated with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARBs) and hydrochlorothiazide at the maximum dosage (25 mg/d).
  
  
  METHODS
  In this randomized, open-label, controlled trial, we enrolled 175 Caucasian patients with essential hypertension not well controlled by concomitant ACE-I or ARBs and hydrochlorothiazide. At baseline, 87 patients (57 males and 30 females) were randomized to add canrenone 50 mg, and 88 (56 males and 32 females) patients to canrenone 100 mg, once a day, for 3 months. At baseline and after 3 months, we evaluated blood pressure (BP), pulse pressure (PP), heart rate (HR), fasting plasma glucose (FPG), homeostasis model assessment insulin (HOMA Index), lipid profile, electrolytes, uric acid, estimated glomerular filtration rate (eGFR), plasma urea, aldosterone, B-type natriuretic peptide (BNP), and galectin-3.
  
  
  RESULTS
  Blood pressure decreased with both dosages of canrenone, with a better effect with canrenone 100 mg (-20.26 vs -23.68 mm Hg for SBP, and -10.58 vs -12.38 mm Hg for DBP), without a clinically relevant increase in potassium levels. We did not observe any differences regarding FPG or HOMA Index, nor of lipid profile, with the exception of triglycerides, which increased compared to baseline with canrenone 50 mg (+0.25 vs +0.34 mEq/L). Creatinine slightly increased with canrenone 100 mg (+0.02 vs +0.05 mg/dL), although no variations of eGFR were observed in neither groups. There was an increase in aldosterone levels with canrenone 50 mg. No changes in BNP or galectin-3 were recorded.
  
  
  CONCLUSIONS
  Both canrenone dosages gave a decrease in blood pressure, with a better effect with the higher dose, with only a slight increase in potassium and creatinine levels, which were not clinically relevant. Clinical Trials Registration Eudract number: 2010-023606-13; ClinicalTrials.gov NCT02687178.
authors.affiliation: Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.|Diabetes and Metabolic Diseases Unit, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.|Centre for Prevention, Surveillance, Diagnosis and Treatment of Rare Diseases, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Derosa
authors.affiliation: Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.|Diabetes and Metabolic Diseases Unit, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.|Centre for Prevention, Surveillance, Diagnosis and Treatment of Rare Diseases, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Maffioli
authors.affiliation: Unit for the treatment of Arterial Hypertension, Ospedale Cardarelli, Napoli, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: D'Avino
authors.affiliation: Unit of Cardiovascular Diseases, Fondazione Policlinico Milano, Milano, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Sala
authors.affiliation: Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
authors.forename: Amedeo
authors.initials: A
authors.lastname: Mugellini
authors.affiliation: Unit for the Diagnosis and Treatment of Arterial Hypertension, Department of Internal Medicine, Policlinico di Bari, Bari, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Vulpis
authors.affiliation: Cardiology Unit, Ospedale Garibaldi, Catania, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Felis
authors.affiliation: Research Center on Dyslipidemia, Internal Medicine 1, University of Insubria, Varese, Italy.
authors.forename: Luigina
authors.initials: L
authors.lastname: Guasti
authors.affiliation: Center for the treatment of Hypertension and Cardiovascular Diseases, Ospedali Riuniti di Torrette, Ancona, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Sarzani
authors.affiliation: THERABEL GiEnne Pharma, Milano, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bestetti
authors.affiliation: THERABEL GiEnne Pharma, Milano, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Vanasia
authors.affiliation: Internal Medicine Division, Ospedale Angelo Bellini, Somma Lombardo, Varese, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Gaudio
mesh_terms: D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage* / Q000009:adverse effects; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D002192:Canrenone / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D000075222:Essential Hypertension; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage* / Q000009:adverse effects; D006973:Hypertension / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D007558:Italy; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D015415:Biomarkers; D000451:Mineralocorticoid Receptor Antagonists; D049993:Sodium Chloride Symporter Inhibitors; D006852:Hydrochlorothiazide; D002192:Canrenone
keywords: Angiotensin II receptor blockers; Angiotensin-converting enzyme inhibitors; Canrenone; Hydrochlorothiazide; Hypertension