Different effects of antihypertensive regimens based on fosinopril or hydrochlorothiazide with or without lipid lowering by pravastatin on progression of asymptomatic carotid atherosclerosis: Principal results of PHYLLIS: A randomized double-blind trial

• Published in: Stroke (1970) Vol. 35; no. 12; pp. 2807 - 2812
• Main Authors: ZANCHETTI, Alberto, CREPALDI, Gaetano, SPERTI, Giovanni, MAGNI, Alberto, BOND, M. Gene, GALLUS, Giuseppe, VEGLIA, Fabrizio, MANCIA, Giuseppe, VENTURA, Alessandro, BAGGIO, Giovannella, SAMPIERI, Lorena, RUBBA, Paolo
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.12.2004
• Subjects: Aged; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Anticholesteremic Agents - therapeutic use; Antihypertensive Agents - therapeutic use; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Carotid Stenosis - complications; Carotid Stenosis - drug therapy; Carotid Stenosis - physiopathology; Disease Progression; Diuretics; Drug Therapy, Combination; Female; Fosinopril - therapeutic use; Humans; Hydrochlorothiazide - therapeutic use; Hypercholesterolemia - complications; Hypercholesterolemia - drug therapy; Hypertension - complications; Hypertension - drug therapy; Male; Medical sciences; Middle Aged; Neurology; Neurosurgery; Pravastatin - therapeutic use; Skull, brain, vascular surgery; Sodium Chloride Symporter Inhibitors - therapeutic use; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Vascular diseases and vascular malformations of the nervous system; lipids; Cardiovascular disease; Asymptomatic; Pravastatin; Vascular disease; Diuretic; arteriosclerosis; Peptidyl-dipeptidase A; Atherosclerosis; Cerebrovascular disease; Blind; Stroke; Nervous system diseases; Enzyme; Enzyme inhibitor; Statin derivative; carotid arteries; Hydrochlorothiazide; Cerebral disorder; Peptidases; Carotid; Central nervous system disease; Hydrolases; Hydroxymethylglutaryl-CoA reductase; Peptidyl-dipeptidases; Antihypertensive agent; Fosinopril; Oxidoreductases; Thiazide; hypertension; ACE inhibitor; Antilipemic agent
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/01.STR.0000147041.00840.59

The Plaque Hypertension Lipid-Lowering Italian Study (PHYLLIS) tested whether (1) the angiotensin-converting enzyme (ACE) inhibitor fosinopril (20 mg per day) was more effective on carotid atherosclerosis progression than the diuretic hydrochlorothiazide (25 mg per day), (2) pravastatin (40 mg per day) was more effective than placebo when added to either hydrochlorothiazide or fosinopril, and (3) there were additive effects of ACE inhibitor and lipid-lowering therapies. A total of 508 hypertensive, hypercholesterolemic patients with asymptomatic carotid atherosclerosis were randomized to: (A) hydrochlorothiazide; (B) fosinopril; (C) hydrochlorothiazide plus pravastatin; and (D) fosinopril plus pravastatin, and followed up blindly for 2.6 years. B-Mode carotid scans were performed yearly by certified sonographers in 13 hospitals and read centrally. Corrections for drift were calculated from readings repeated at study end. Primary outcome was change in mean maximum intima-media thickness of far and near walls of common carotids and bifurcations bilaterally (CBM(max)). CBM(max) significantly progressed (0.010+/-0.004 mm per year; P=0.01) in group A (hydrochlorothiazide alone) but not in groups B, C, and D. CBM(max) changes in groups B, C, and D were significantly different from changes in group A. Changes in group A were concentrated at the bifurcations. "Clinic" and "ambulatory" blood pressure reductions were not significantly different between groups, but total and low-density lipoprotein cholesterol decreased by approximately 1 mmol/L in groups C and D. Progression of carotid atherosclerosis occurred with hydrochlorothiazide but not with fosinopril. Progression could also be avoided by associating pravastatin with hydrochlorothiazide.