title: Efficacy of Zofenopril vs. Irbesartan in Combination with a Thiazide Diuretic in Hypertensive Patients with Multiple Risk Factors not Controlled by a Previous Monotherapy: A Review of the Double-Blind, Randomized "Z" Studies.
abstract: Combinations between an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) and hydrochlorothiazide (HCTZ) are among the recommended treatments for hypertensive patients uncontrolled by monotherapy. Four randomized, double-blind, parallel group studies with a similar design, including 1469 hypertensive patients uncontrolled by a previous monotherapy and with ≥1 cardiovascular risk factor, compared the efficacy of a combination of a sulfhydryl ACE inhibitor (zofenopril at 30 or 60 mg) or an ARB (irbesartan at 150 or 300 mg) plus HCTZ 12.5 mg. The extent of blood pressure (BP)-lowering was assessed in the office and over 24 h. Pleiotropic features of the treatments were evaluated by studying their effect on systemic inflammation, organ damage, arterial stiffness, and metabolic biochemical parameters. Both treatments similarly reduced office and ambulatory BPs after 18-24 weeks. In the ZODIAC study a larger reduction in high sensitivity C reactive protein (hs-CRP) was observed under zofenopril (-0.52 vs. +0.97 mg/dL under irbesartan, p = 0.001), suggesting a potential protective effect against the development of atherosclerosis. In the ZENITH study the rate of carotid plaque regression was significantly larger under zofenopril (32% vs. 16%; p = 0.047). In the diabetic patients of the ZAMES study, no adverse effects of treatments on blood glucose and lipids as well as an improvement of renal function were observed. In patients with isolated systolic hypertension of the ZEUS study, a slight and similar improvement in renal function and small reductions in pulse wave velocity (PWV), augmentation index (AI), and central systolic BP were documented with both treatments. Thus, the fixed combination of zofenopril and HCTZ may have a relevant place in the treatment of high-risk or monotherapy-treated uncontrolled hypertensive patients requiring a more prompt, intensive, and sustained BP reduction, in line with the recommendations of current guidelines.
authors.affiliation: Clinical Research Unit, Italian Institute of Telemedicine, Varese, Italy. stefano.omboni@iitelemed.org.
authors.forename: Stefano
authors.identifier: 0000-0002-7124-2096
authors.initials: S
authors.lastname: Omboni
authors.affiliation: L. Sacco Hospital, Milan, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Malacco
authors.affiliation: Department of Internal Medicine and Specialistic Units, U.O.C. of Clinical Immunology, Immunohematology, Transfusion Medicine and Organ Transplantation, Azienda Ospedaliera Universitaria (AOU), Second University of Naples, Naples, Italy.|SDN Foundation and IRCCS, Naples, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Napoli
authors.affiliation: Department of Clinical and Experimental Medicine, Careggi Hospital, University of Florence, Florence, Italy.
authors.forename: Pietro Amedeo
authors.initials: PA
authors.lastname: Modesti
authors.affiliation: Asklepeion General Hospital of Voula, University of Athens, Athens, Greece.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Manolis
authors.affiliation: Department of Cardiovascular, Neural and Metabolic Sciences, Istituto Auxologico Italiano, Milan, Italy.|Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Parati
authors.affiliation: Division of Medicine and Surgery, Spedali Civili and University of Brescia, Brescia, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Agabiti-Rosei
authors.affiliation: Department of Internal Medicine, University of Bologna, Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Borghi
mesh_terms: D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D001786:Blood Glucose; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D002216:Captopril / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003920:Diabetes Mellitus / Q000453:epidemiology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000453:epidemiology; D018836:Inflammation Mediators / Q000378:metabolism; D000077405:Irbesartan; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D063177:Pulse Wave Analysis; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D059289:Vascular Stiffness
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D015415:Biomarkers; D001713:Biphenyl Compounds; D001786:Blood Glucose; D018836:Inflammation Mediators; D008055:Lipids; D013777:Tetrazoles; D006852:Hydrochlorothiazide; C044958:zofenopril; D002097:C-Reactive Protein; D002216:Captopril; D000077405:Irbesartan
keywords: Ambulatory blood pressure; Angiotensin II receptor blockers; Angiotensin converting enzyme inhibitors; Essential hypertension; Hydrochlorothiazide; Irbesartan; Office blood pressure; Thiazide diuretics; Zofenopril