Circulation. 2002;106:2422-2427
Published online before print October 21, 2002, doi: 10.1161/01.CIR.0000039288.86470.DD
Published online before print October 21, 2002, doi: 10.1161/01.CIR.0000039288.86470.DD
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2002;106:2422.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
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
From the University of Milan, Ospedale Maggiore, Istituto Auxologico Italiano, Milan, Italy (A.Z.); Wake Forest University School of Medicine, Winston-Salem, NC (M.G.B.); Technische Universität München, Munich, Germany (M.H., A.N.); University of Milano-Bicocca, Monza, Italy (G.M.); University of Padua, Padua, Italy (C.D.P.); University of Uppsala, Uppsala, Sweden (L.H.); University of Bologna, Bologna, Italy (B.M.); Westfälische Wilhelm-Universität Münster, Münster, Germany (K.H.R); University of Glasgow, Glasgow, UK (J.L.R.); 12 de Octubre Hospital, Madrid, Spain (J.R.); Hôpital Broussais, Paris, France (M.S.); Boehringer Ingelheim Pharma KG, Ingelheim am Rhein, Germany (L.E.); and GlaxoSmithKline Italy, Verona, Italy (P.R.).
Correspondence to Prof Alberto Zanchetti, Centro di Fisiologia Clinica e Ipertensione, Via F. Sforza, 35, 20122 Milano, Italy. E-mail zanchett{at}mailserver.unimi.it
Background— Most cardiovascular events associated with hypertension are complications of atherosclerosis. Some antihypertensive agents influence experimental models of atherosclerosis through mechanisms independent of blood pressure lowering.
Methods and Results— The European Lacidipine Study on Atherosclerosis (ELSA) was a randomized, double-blind trial in 2334 patients with hypertension that compared the effects of a 4-year treatment based on either lacidipine or atenolol on an index of carotid atherosclerosis, the mean of the maximum intima-media thicknesses (IMT) in far walls of common carotids and bifurcations (CBMmax). This index has been shown by epidemiological studies to be predictive of cardiovascular events. A significant (P<0.0001) effect of lacidipine was found compared with atenolol, with a treatment difference in 4-year CBMmax progression of -0.0227 mm (intention-to-treat population) and -0.0281 mm (completers). The yearly IMT progression rate was 0.0145 mm/y in atenolol-treated and 0.0087 mm/y in lacidipine-treated patients (completers, 40% reduction; P=0.0073). Patients with plaque progression were significantly less common, and patients with plaque regression were significantly more common in the lacidipine group. Clinic blood pressure reductions were identical with both treatments, but 24-hour ambulatory systolic/diastolic blood pressure changes were greater with atenolol (-10/-9 mm Hg) than with lacidipine (-7/-5 mm Hg). No significant difference between treatments was found in any cardiovascular events, although the relative risk for stroke, major cardiovascular events, and mortality showed a trend favoring lacidipine.
Conclusion— The greater efficacy of lacidipine on carotid IMT progression and number of plaques per patient, despite a smaller ambulatory blood pressure reduction, indicates an antiatherosclerotic action of lacidipine independent of its antihypertensive action.
Key Words: atherosclerosis • carotid arteries • plaque • hypertension • drugs
This article has been cited by other articles:
 |
|
 |
|
  C. Cuspidi, F. Negri, V. Giudici, and C. Sala Retinal changes and cardiac remodelling in systemic hypertension Therapeutic Advances in Cardiovascular Disease, June 1, 2009; 3(3): 205 - 214. [Abstract] [PDF]
|
|
|
|
 |
|
 G. Brevetti, G. Sirico, G. Giugliano, S. Lanero, J. I. De Maio, R. Luciano, E. Laurenzano, and M. Chiariello Prevalence of hypoechoic carotid plaques in coronary artery disease: relationship with coexistent peripheral arterial disease and leukocyte number Vascular Medicine, February 1, 2009; 14(1): 13 - 19. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Puato, P. Palatini, M. Zanardo, F. Dorigatti, C. Tirrito, M. Rattazzi, and P. Pauletto Increase in Carotid Intima-Media Thickness in Grade I Hypertensive Subjects: White-Coat Versus Sustained Hypertension Hypertension, May 1, 2008; 51(5): 1300 - 1305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. V. Howard, M. J. Roman, R. B. Devereux, J. L. Fleg, J. M. Galloway, J. A. Henderson, Wm. J. Howard, E. T. Lee, M. Mete, B. Poolaw, et al. Effect of Lower Targets for Blood Pressure and LDL Cholesterol on Atherosclerosis in Diabetes: The SANDS Randomized Trial JAMA, April 9, 2008; 299(14): 1678 - 1689. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. O. Stumpe, E. Agabiti-Rosei, T. Zielinski, D. Schremmer, J. Scholze, P. Laeis, P. Schwandt, and M. Ludwig 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 Therapeutic Advances in Cardiovascular Disease, December 1, 2007; 1(2): 97 - 106. [Abstract] [PDF]
|
|
|
|
 |
|
 G. Onder, E. Capoluongo, M. Cesari, P. Lulli, R. Liperoti, B. Giardina, A. Russo, R. Bernabei, and F. Landi Association of Calcium Channel Blocker Use and Pregnancy-Associated Plasma Protein-A Among Older Adults With Hypertension: Results From the ilSIRENTE Study J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2007; 62(11): 1274 - 1278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Authors/Task Force Members, I. Graham, D. Atar, K. Borch-Johnsen, G. Boysen, G. Burell, R. Cifkova, J. Dallongeville, G. De Backer, S. Ebrahim, et al. European guidelines on cardiovascular disease prevention in clinical practice: executive summary: Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (Constituted by representatives of nine societies and by invited experts) Eur. Heart J., October 1, 2007; 28(19): 2375 - 2414. [Full Text] [PDF]
|
|
|
|
|
|
Authors/Task Force Members:, G. Mancia, G. De Backer, A. Dominiczak, R. Cifkova, R. Fagard, G. Germano, G. Grassi, A. M. Heagerty, S. E. Kjeldsen, et al. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) Eur. Heart J., June 11, 2007; (2007) ehm236v1. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Yanai, H. Yoshida, Y. Tomono, and N. Tada Atherosclerosis imaging in statin intervention trials QJM, May 1, 2007; 100(5): 253 - 262. [Full Text] [PDF]
|
|
|
|
|
|
T. Mazzone, P. M. Meyer, S. B. Feinstein, M. H. Davidson, G. T. Kondos, R. B. D'Agostino Sr, A. Perez, J.-C. Provost, and S. M. Haffner Effect of Pioglitazone Compared With Glimepiride on Carotid Intima-Media Thickness in Type 2 Diabetes: A Randomized Trial JAMA, December 6, 2006; 296(21): 2572 - 2581. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Crouse III Thematic review series: Patient-Oriented Research. Imaging atherosclerosis: state of the art J. Lipid Res., August 1, 2006; 47(8): 1677 - 1699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-G. Wang, J. A. Staessen, Y. Li, L. M. Van Bortel, T. Nawrot, R. Fagard, F. H. Messerli, and M. Safar Carotid Intima-Media Thickness and Antihypertensive Treatment: A Meta-Analysis of Randomized Controlled Trials Stroke, July 1, 2006; 37(7): 1933 - 1940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. S. Sever, N. R. Poulter, W. J. Elliott, M. C. Jonsson, H. R. Black, P. S. Sever, N. R. Poulter, W. J. Elliott, M. C. Jonsson, and H. R. Black Blood Pressure Reduction Is Not the Only Determinant of Outcome Circulation, June 13, 2006; 113(23): 2754 - 2774. [Full Text] [PDF]
|
|
|
|
 |
|
 N. Khan and F. A. McAlister Re-examining the efficacy of {beta}-blockers for the treatment of hypertension: a meta-analysis Can. Med. Assoc. J., June 6, 2006; 174(12): 1737 - 1742. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Lucas, R. Korol, and C. J. Pepine Inflammation in Atherosclerosis: Some Thoughts About Acute Coronary Syndromes Circulation, May 2, 2006; 113(17): e728 - e732. [Full Text] [PDF]
|
|
|
|
 |
|
 J.-P. Baguet, L. Hammer, P. Levy, H. Pierre, S. Launois, J.-M. Mallion, and J.-L. Pepin The Severity of Oxygen Desaturation Is Predictive of Carotid Wall Thickening and Plaque Occurrence Chest, November 1, 2005; 128(5): 3407 - 3412. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kyselovic, P. Martinka, Z. Batova, A. Gazova, and T. Godfraind Calcium Channel Blocker Inhibits Western-Type Diet-Evoked Atherosclerosis Development in ApoE-Deficient Mice J. Pharmacol. Exp. Ther., October 1, 2005; 315(1): 320 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.-J. Touboul, J. Labreuche, E. Vicaut, P. Amarenco, and on behalf of the GENIC Investigators Carotid Intima-Media Thickness, Plaques, and Framingham Risk Score as Independent Determinants of Stroke Risk Stroke, August 1, 2005; 36(8): 1741 - 1745. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Verdecchia, G. Reboldi, F. Angeli, R. Gattobigio, M. Bentivoglio, L. Thijs, J. A. Staessen, and C. Porcellati Angiotensin-Converting Enzyme Inhibitors and Calcium Channel Blockers for Coronary Heart Disease and Stroke Prevention Hypertension, August 1, 2005; 46(2): 386 - 392. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Blood Pressure Lowering Treatment Trialists' Colla Effects of Different Blood Pressure-Lowering Regimens on Major Cardiovascular Events in Individuals With and Without Diabetes Mellitus: Results of Prospectively Designed Overviews of Randomized Trials Arch Intern Med, June 27, 2005; 165(12): 1410 - 1419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Shinoda, Y. Yui, K. Kodama, A. Hirayama, H. Nonogi, K. Haze, T. Sumiyoshi, S. Hosoda, C. Kawai, and for the Japan Multicenter Investigation for Cardio Quantitative Coronary Angiogram Analysis: Nifedipine Retard Versus Angiotensin-Converting Enzyme Inhibitors (JMIC-B Side Arm Study) Hypertension, June 1, 2005; 45(6): 1153 - 1158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Zakopoulos, G. Tsivgoulis, G. Barlas, C. Papamichael, K. Spengos, E. Manios, I. Ikonomidis, V. Kotsis, I. Spiliopoulou, K. Vemmos, et al. Time Rate of Blood Pressure Variation Is Associated With Increased Common Carotid Artery Intima-Media Thickness Hypertension, April 1, 2005; 45(4): 505 - 512. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Williams Recent hypertension trials: Implications and controversies J. Am. Coll. Cardiol., March 15, 2005; 45(6): 813 - 827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liao, M. Asakura, S. Takashima, A. Ogai, Y. Asano, H. Asanuma, T. Minamino, H. Tomoike, M. Hori, and M. Kitakaze Benidipine, a long-acting calcium channel blocker, inhibits cardiac remodeling in pressure-overloaded mice Cardiovasc Res, March 1, 2005; 65(4): 879 - 888. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Kahn, K. Boesze-Battaglia, D. W. Stepp, A. Petrov, Y. Huang, R. P. Mason, and T. N. Tulenko Influence of serum cholesterol on atherogenesis and intimal hyperplasia after angioplasty: inhibition by amlodipine Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H591 - H600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zanchetti, G. Crepaldi, M. G. Bond, G. Gallus, F. Veglia, G. Mancia, A. Ventura, G. Baggio, L. Sampieri, P. Rubba, et al. 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 Stroke, December 1, 2004; 35(12): 2807 - 2812. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Magyar, G. Paragh, E. Katona, A. Valikovics, I. Seres, L. Csiba, and D. Bereczki Serum Cholesterols Have a More Important Role Than Triglycerides in Determining Intima-Media Thickness of the Common Carotid Artery in Subjects Younger Than 55 Years of Age J. Ultrasound Med., September 1, 2004; 23(9): 1161 - 1169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Fournier, F. H. Messerli, J. M. Achard, and L. Fernandez Cerebroprotection mediated by angiotensin II: A hypothesis supported by recent randomized clinical trials J. Am. Coll. Cardiol., April 21, 2004; 43(8): 1343 - 1347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Scuteri, S. S. Najjar, D. C. Muller, R. Andres, H. Hougaku, E. J. Metter, and E. G. Lakatta Metabolic syndrome amplifies the age-associated increases in vascular thickness and stiffness J. Am. Coll. Cardiol., April 21, 2004; 43(8): 1388 - 1395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M.M. Lawes, D. A. Bennett, V. L. Feigin, and A. Rodgers Blood Pressure and Stroke: An Overview of Published Reviews Stroke, April 1, 2004; 35(4): 1024 - 1033. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Candido, T. J. Allen, M. Lassila, Z. Cao, V. Thallas, M. E. Cooper, and K. A. Jandeleit-Dahm Irbesartan but Not Amlodipine Suppresses Diabetes-Associated Atherosclerosis Circulation, March 30, 2004; 109(12): 1536 - 1542. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M.M. Lawes, D. A. Bennett, V. L. Feigin, and A. Rodgers Blood Pressure and Stroke: An Overview of Published Reviews Stroke, March 1, 2004; 35(3): 776 - 785. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Pontremoli, G. Leoncini, F. Viazzi, D. Parodi, E. Ratto, S. Vettoretti, M. Ravera, C. Tomolillo, and G. Deferrari Cardiovascular and Renal Risk Assessment as a Guide for Treatment in Primary Hypertension J. Am. Soc. Nephrol., January 1, 2004; 15(90010): S34 - 36. [Abstract] [Full Text]
|
|
|
|
 |
|
 R.P. Mason, P. Marche, and T.H. Hintze Novel Vascular Biology of Third-Generation L-Type Calcium Channel Antagonists: Ancillary Actions of Amlodipine Arterioscler. Thromb. Vasc. Biol., December 1, 2003; 23(12): 2155 - 2163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Pockley, A. Georgiades, T. Thulin, U. de Faire, and J. Frostegard Serum Heat Shock Protein 70 Levels Predict the Development of Atherosclerosis in Subjects With Established Hypertension Hypertension, September 1, 2003; 42(3): 235 - 238. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Lipskaia, M.-L. Pourci, C. Delomenie, L. Combettes, D. Goudouneche, J.-L. Paul, T. Capiod, and A.-M. Lompre Phosphatidylinositol 3-Kinase and Calcium-Activated Transcription Pathways Are Required for VLDL-Induced Smooth Muscle Cell Proliferation Circ. Res., May 30, 2003; 92(10): 1115 - 1122. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Psaty, T. Lumley, C. D. Furberg, G. Schellenbaum, M. Pahor, M. H. Alderman, and N. S. Weiss Health Outcomes Associated With Various Antihypertensive Therapies Used as First-Line Agents: A Network Meta-analysis JAMA, May 21, 2003; 289(19): 2534 - 2544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Opie Anti-ischemic properties of calcium-channel blockers: Lessons from cardiac surgery J. Am. Coll. Cardiol., May 7, 2003; 41(9): 1506 - 1509. [Full Text] [PDF]
|
|