Zanchetti Alberto, Crepaldi Gaetano, Bond M Gene, Gallus Giuseppe, Veglia Fabrizio, Mancia Giuseppe, Ventura Alessandro, Baggio Giovannella, Sampieri Lorena, Rubba Paolo, Sperti Giovanni, Magni Alberto
Istituto Auxologico Italiano, Ospedale Maggiore, University of Milan, Italy.
Stroke. 2004 Dec;35(12):2807-12. doi: 10.1161/01.STR.0000147041.00840.59. Epub 2004 Oct 28.
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.
意大利斑块高血压降脂研究（PHYLLIS）旨在检验：（1）血管紧张素转换酶（ACE）抑制剂福辛普利（每日20毫克）在延缓颈动脉粥样硬化进展方面是否比利尿剂氢氯噻嗪（每日25毫克）更有效；（2）普伐他汀（每日40毫克）与氢氯噻嗪或福辛普利联合使用时是否比安慰剂更有效；（3）ACE抑制剂与降脂治疗是否具有相加作用。
共有508例患有无症状颈动脉粥样硬化的高血压、高胆固醇血症患者被随机分为：（A）氢氯噻嗪组；（B）福辛普利组；（C）氢氯噻嗪加普伐他汀组；（D）福辛普利加普伐他汀组，并进行了2.6年的盲法随访。13家医院的认证超声检查人员每年进行B型颈动脉扫描，并进行集中解读。根据研究结束时重复测量的结果计算漂移校正值。主要结局指标是双侧颈总动脉和分叉处远、近壁平均最大内膜中层厚度的变化（CBM(max)）。
A组（仅氢氯噻嗪组）的CBM(max)显著进展（每年0.010±0.004毫米；P = 0.01），而B、C和D组未出现进展。B、C和D组的CBM(max)变化与A组显著不同。A组的变化集中在分叉处。各组间“诊室”和“动态”血压降低情况无显著差异，但C组和D组的总胆固醇和低密度脂蛋白胆固醇降低了约1毫摩尔/升。
氢氯噻嗪会导致颈动脉粥样硬化进展，而福辛普利则不会。普伐他汀与氢氯噻嗪联合使用也可避免进展。
