Original Research: Carotid intima-media thickness and plaque volume changes following 2-year angiotensin II-receptor blockade. The Multicentre Olmesartan atherosclerosis Regression Evaluation (MORE) study
Objective The Multicentre Olmesartan atherosclerosis Regression Evaluation (MORE) study was a double-blind trial in patients with hypertension at increased cardiovascular risk with carotid wall thickening and a defined atherosclerotic plaque that used non-invasive 2- and 3-dimensionaL (D) ultrasound (US), to compare the effects of a 2-year treatment based on either olmesartan medoxomil or atenolol on common carotid (CC) intima-media thickness (IMT) and plaque volume (PV).
Methods A total of 165 patients (with systolic/diastolic blood pressure 140—180/ 90—105 mmHg) were randomized to receive either olmesartan (20—40 mg/day) or atenolol (50—100 mg/day). US was performed at baseline and 28, 52 and 104 weeks. The primary efficacy outcome was the change from baseline ( Δ) in CC-IMT assessed by 2D US. Secondary outcomes included Δ PV assessed by 3D US and blood pressure (BP).
Results Olmesartan and atenolo produced comparable significant reductions in CC-IMT; mean Δ IMT (SEM) was -0.090 (0.015) mm for oLmesartan and -0.082 (0.014) mm for atenolol. Mean Δ PV was -4.4 (2.3) µl and 0.1 (1.5) µl in the olmesartan and atenolol treated subjects, respectively, without significant between-treatment differences. In the subgroup of patients with baseLine PV ≥ median (33.7 µl), significant between-treatment differences existed in Δ PV (p = 0.023), because PV regressed significantly with olmesartan (Δ PV: -11.5 (4.4) µl) but not with atenolol ( Δ PV: 0.6 (2.5) µl). In these patients BP reductions were comparabLe.
Conclusions Carotid IMT and BP decreased similarly with olmesartan and atenolol, but only olmesartan reduced the volume of larger atherosclerotic plaques.
Ariff, B. et al. (2006) Candesartan- and atenolol-based treatments induce different patterns of carotid artery and left ventricular remodelling in hypertension . Stroke37: 2381—2384 .
2.
Boutouyrie, P. et al. (2000) Local pulse pressure, and regression of arterial wall hypertrophy during long-term antihypertensive treatment . Circulation101: 2601—2606 .
3.
Carlberg, B. et al. (2004) Atenolol in hypertension: is it a wise choice?Lancet364: 1684—1689 .
4.
Chobanian, A.V. (1990) 1989 Corcoran lecture: Adaptive and maladaptive response of the arterial wall to hypertension . Hypertension15: 666—674 .
5.
Fenster, A. et al. (2001) Three-dimensional ultrasound imaging . Phys Med Biol46: 67—99 .
6.
Landry, A. et al. (2004) Measurement of carotid plaque volume by 3-dimensional ultrasound . Stroke35: 864—869 .
7.
Linhart, A. et al. (1996) Carotid artery and left ventricular structural relationship in asymptomatic men at risk for cardiovascular disease . Atherosclerosis15: 127 : 103—112 .
8.
Lorenz, M.W. et al. (2007) Prediction of clinical cardiovascular events with carotid intima-media thickness . Circulation2007; 115: 459—467 .
9.
Ludwig, M. (1997) 3D-Sonographie . Klinische Angiologie137—175 .
10.
Ludwig, M. et al. (1998) Limitations of 2-dimensional (D)-ultrasound imaging for the quantitative assessment of common carotid artery atherosclerosis: superiority of high-resolution 3-D-ultrasonography . J Hypertens16(suppl 12): S104 .
11.
Ludwig, M. et al. (2002) Comparison of the effects of losartan and atenolol on common carotid artery intima-media thickness in patients with hypertension: results of a 2-year, double-blind, randomized, controlled study . Clin Ther24: 1175—1193 .
12.
Ludwig, M. et al. (2007) Reproducibility of 3D-ultrasound assessment of carotid plaque in patients with cardiovascular risk . Atherosclerosis2007; 8(suppl 1): S134 .
13.
Mintz, G.S. et al. (2001) American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies (IVUS): a report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents . J Am Coll Cardiol37: 1478—1492 .
14.
Miyazaki, M. and Takai, S. (2002) Anti-atherosclerotic efficacy of olmesartan . J Hum Hypertens16(suppl 2): S7—12 .
15.
Nickenig, G. and Harrison, D.G. (2002) The AT(1)-type angiotensin receptor in oxidative stress and atherogenesis: part I: oxidative stress and atherogenesis . Circulation105: 393—396 .
16.
Olsen, M.H. et al. (2005) Losartan but not atenolol reduce carotid artery hypertrophy in essential hypertension. A LIFE substudy . Blood Press14: 177—183 .
17.
Parker, G.W. et al. (1990) Central beta-adrenergic mechanism may modulate ischaemic ventricular fibrillation in pigs . Circ Res66: 259—270 .
18.
Persson, J. et al. (1994) Ultrasound-determined intima-media thickness and atherosclerosis. Direct and indirect validation . Arterioscler Thromb14: 261—264 .
19.
Shoukri, M.M. (2004) Reliability for continuous scale measurements. In Shoukri, M.M. Measures of interobserver agreement. Chapman & Hall/CRC: Boca Raton .
20.
Shrout, P.E. and Fleiss, J.L. (1979) Intraclass correlations: Uses in assessing rater reliability . Psychological Bulletin86: 420—428 .
21.
Strawn,W.B. et al. (2000) Inhibition of early atherogenesis by losartan in monkeys with diet-induced hypercholesterolemia . Circulation101: 1586—1593 .
22.
Takai, S. et al. (2005) The regressive effect of an angiotensin II receptor blocker on formed fatty streaks in monkeys fed a high-cholesterol diet . J Hypertens23: 1879—1886 .
23.
Wang, J.G. et al. (2006) Carotid intima-media thickness and antihypertensive treatment:
24.
a meta-analysis of randomized controlled trials . Stroke37(7): 1933—1940 .
25.
Wassmann, S. et al. (2004) Inhibition of diet-induced atherosclerosis and endothelial dysfunction in apolipoprotein E/angiotensin II type 1A receptor double-knockout mice . Circulation110: 3062—3067 .
26.
Williams, B. et al. (2006) Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study . Circulation113(9): 1213—1225 .
27.
Zanchetti, A. et al. (1998) The Verapamil in Hypertension and Atherosclerosis Study (VHAS): results of long-term randomized treatment with either verapamil or chlorthalidone on carotid intima-media thickness . J Hypertens16: 1667—1676 .
28.
Zanchetti, A. et al. (2002) Calcium antagonist lacidipine slows down progression of asymptomatic carotid atherosclerosis. Principal results of the European Lacidipine Study on Atherosclerosis (ELSA), a randomized, double-blind, long-term trial . Circulation106: 2422—2427 .
