BACKGROUND AND PURPOSE: 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. METHODS: 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)). RESULTS: 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. CONCLUSIONS:Progression of carotid atherosclerosis occurred with hydrochlorothiazide but not with fosinopril. Progression could also be avoided by associating pravastatin with hydrochlorothiazide.
RCT Entities:
BACKGROUND AND PURPOSE: The Plaque HypertensionLipid-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. METHODS: A total of 508 hypertensive, hypercholesterolemicpatients 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)). RESULTS: 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. CONCLUSIONS: Progression of carotid atherosclerosis occurred with hydrochlorothiazide but not with fosinopril. Progression could also be avoided by associating pravastatin with hydrochlorothiazide.
Authors: Marcello Tonelli; Anita Lloyd; Fiona Clement; Jon Conly; Don Husereau; Brenda Hemmelgarn; Scott Klarenbach; Finlay A McAlister; Natasha Wiebe; Braden Manns Journal: CMAJ Date: 2011-10-11 Impact factor: 8.262
Authors: Donald M Lloyd-Jones; Mark D Huffman; Kunal N Karmali; Darshak M Sanghavi; Janet S Wright; Colleen Pelser; Martha Gulati; Frederick A Masoudi; David C Goff Journal: Circulation Date: 2016-11-04 Impact factor: 29.690
Authors: J J Brugts; T Yetgin; S E Hoeks; A M Gotto; J Shepherd; R G J Westendorp; A J M de Craen; R H Knopp; H Nakamura; P Ridker; R van Domburg; J W Deckers Journal: BMJ Date: 2009-06-30
Authors: Fiona Taylor; Mark D Huffman; Ana Filipa Macedo; Theresa H M Moore; Margaret Burke; George Davey Smith; Kirsten Ward; Shah Ebrahim Journal: Cochrane Database Syst Rev Date: 2013-01-31
Authors: Donald M Lloyd-Jones; Mark D Huffman; Kunal N Karmali; Darshak M Sanghavi; Janet S Wright; Colleen Pelser; Martha Gulati; Frederick A Masoudi; David C Goff Journal: J Am Coll Cardiol Date: 2016-11-04 Impact factor: 24.094