Different Effects of Antihypertensive Regimens Based on Fosinopril or Hydrochlorothiazide With or Without Lipid Lowering by Pravastatin on Progression of Asymptomatic Carotid Atherosclerosis

Abstract

on behalf of PHYLLIS InvestigatorsBackground 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 (0.010Ϯ0.004 mm per year; Pϭ0.01) 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 Ϸ1 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. (Stroke. 2004;35:2807-2812.)

Efficacy of statins for primary prevention in people at low cardiovascular risk: a meta-analysis

“…Length of hospital stay, persistence on statin therapy and quality-of-life measures were not reported in any of the studies. ALLHAT-LLT 40 Bruckert et al 33 Muldoon et al 29 PHYLLIS 30 PREVEND-IT 31 Rejnmark et al 32 HYRIM 28 MEGA 24 ASCOT-LLA 36 Holmberg et al 26 Bone et al 23 Adverse events Twenty-one trials (n = 47 589) reported the number of participants who had serious adverse events. The trial-level relative risk could not be estimated for four trials that reported no events in either group.…”

Mean Common or Mean Maximum Carotid Intima-Media Thickness as Primary Outcome in Lipid-Modifying Intervention Studies

“…In eight CIMT trials, the results showed a similar direction for both CIMT and event outcome measurements, while in seven CIMT trials, congruency with event trials depended on the choice of the primary outcome measure. In four trials 10, 12, 22,30) , expected effects were found for the mean maximum CIMT but not for the common CIMT for mean, whereas in three trials 8, 13, 15) an effect was found for the common CIMT and not for the mean maximum CIMT. Thus, when relying on the mean maximum CIMT only, three trials would have been falsely negative (no effect on CIMT, clear clinical events effect).…”

“…Through a reference check one additional trial was identified 32) . Ultimately, this resulted in 15 CIMT trials for analyses 5, 7-10, 12, 13, 15, 16, 18,19,21,22,30,32) . For each drug used in the CIMT trials, the corresponding event trials were searched, resulting in 15 clinical event trials for lovastatin, pravastatin, fluvastatin, simvastatin, atorvastatin, torcetrapib, rosuvastatin and ezetimibe, as presented in Table 2 [33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49] .…”

“…For three trials 8,13,30) , information on reproducibility could not be retrieved from the publication ( Table 2). Reproducibility was expressed in various manners and for different processes (re-reading/ repeated visits).…”

Protective effects of renin–angiotensin blockade beyond blood pressure control

“…3 Similar results have been obtained in other trials such as the Hypertension Optimal Treatment (HOT), 4 the International Nifedipine GITS study Intervention as a Goal in Hypertension Treatment (INSIGHT) 5 and the Plaque Hypertension Lipid-Lowering Italian Study (PHYLLIS). 6 Blood pressure control and cardiovascular outcome…”