Print Email Facebook Twitter Amlodipine and atorvastatin in atherosclerosis Title Amlodipine and atorvastatin in atherosclerosis: A review of the potential of combination therapy Author TNO Preventie en Gezondheid Jukema, J.W. van der Hoorn, J.W.A. Publication year 2004 Abstract Hypertension and hyperlipidaemia are major risk factors for the development of atherosclerosis. Calcium channel blockers (CCBs) have been used for decades and have established antihypertensive effects. Statins have been extensively used because of their potent lipid lowering properties. Amongst other factors, inflammation and oxidation are involved in enhanced progression of atherosclerosis and new lesion development. Therefore, research has been initiated focusing on the antioxidant and anti-inflammatory properties of CCBs and statins, beyond their primary effect, in order to evaluate the possible additive effects of combined treatment of CCBs with statins as antiatherosclerotic therapy. Clinical studies (e.g., the International Nifedipine Trial on Antiatherosclerotic Therapy [INTACT]) have demonstrated that the antiatherosclerotic action of CCBs is limited to the attenuation of the first stage of atherosclerogenesis (fatty streak formation or new lesion growth). The lesions that pre-existed at the start of CCB therapy did not demonstrate progression or regression on angiography. However, because the mechanisms of action of lipid-lowering drugs and CCBs, and their role in preventing the progression of atherosclerosis differ, it is conceivable to conclude that these two classes may have an additive or synergic effect, not only on new lesion formation but also on inhibiting the progression of established coronary atherosclerosis. Indeed, this combined effect of lipid-lowering therapy and CCBs on human coronary atherosclerosis has been reported in the Regression Growth Evaluation Statin Study (REGRESS) trial. This beneficial effect of combining CCBs with statins has now been replicated in transgenic atherosclerotic mice, where the combination of amlodipine and atorvastatin produced an additional 60% reduction of atherosclerosis compared with that observed with the statin alone. Serum markers of atherosclerosis and vascular integrity also improved most in the combination group. Synergistic effects of the combination of atorvastatin and amlodipine on acute nitric oxide release/endothelial function, and additive effects of the combination of amlodipine and atorvastatin in the improvement of arterial compliance in hypertensive hyperlipidaemic patients has been demonstrated. Collectively, these studies support the clinical antiatherosclerotic advantages of combination of CCBs and statins and in particular, of atorvastatin with amlodipine beyond their established antihyperlipidaemic and antihypertensive modes of action. Chemicals / CAS: alpha tocopherol, 1406-18-4, 1406-70-8, 52225-20-4, 58-95-7, 59-02-9; amlodipine, 88150-42-9; atenolol, 29122-68-7; atorvastatin, 134523-00-5, 134523-03-8; diltiazem, 33286-22-5, 42399-41-7; DNA, 9007-49-2; fibrinogen, 9001-32-5; fluindostatin, 93957-54-1; gelatinase A, 146480-35-5; intercellular adhesion molecule 1, 126547-89-5; interleukin 8, 114308-91-7; lacidipine, 103890-78-4; lipid, 66455-18-3; mevinolin, 75330-75-5; nifedipine, 21829-25-4; nitric oxide, 10102-43-9; pravastatin, 81131-74-0; ramiprilat, 87269-97-4; rosuvastatin, 147098-18-8, 147098-20-2; simvastatin, 79902-63-9; thrombin, 9002-04-4; Amlodipine, 88150-42-9; Antilipemic Agents; atorvastatin, 110862-48-1; Calcium Channel Blockers; Heptanoic Acids; Pyrroles. Subject Biomedical ResearchAmlodipineAtherosclerosisAtorvastatinCombination therapyInflammationOxidationalpha tocopherolamlodipineatenololatorvastatincalcium channel blocking agentdiltiazemdipeptidyl carboxypeptidase inhibitorDNAfibrinogenfluindostatingelatinase Ahydroxymethylglutaryl coenzyme A reductase inhibitorimmunoglobulin enhancer binding proteinintercellular adhesion molecule 1interleukin 6interleukin 8lacidipinelipidlow density lipoproteinmevinolinnifedipinenitric oxidepravastatinramiprilatreactive oxygen metaboliterosuvastatinsimvastatinthrombinunindexed drugvascular cell adhesion molecule 1angiographyantihypertensive activityantiinflammatory activityantioxidant activityartery complianceatherosclerosisblood vessel parameterscardiovascular diseaseclinical studyclinical trialcoronary artery atherosclerosisdisease coursedrug mechanismdrug potentiationhumanhyperlipidemiahypertensionnonhumanreviewrisk factortransgenic mouseAmlodipineAnimalsAntilipemic AgentsArteriosclerosisCalcium Channel BlockersCombined Modality TherapyHeptanoic AcidsHumansHypertensionPyrroles To reference this document use: http://resolver.tudelft.nl/uuid:f21965b3-183b-4357-9e9e-a9f78b5e6967 DOI https://doi.org/10.1517/146565126.96.36.1999 TNO identifier 237614 ISSN 1465-6566 Source Expert Opinion on Pharmacotherapy, 5 (5), 459-468 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.