Fenofibrate

The most common cause of morbidity and mortality in people with type 2 diabetes is cardiovascular disease. Accelerated coronary heart disease, diabetic cardiomyopathy and diabetic autonomic neuropathy contribute to this burden, and the mortality from coronary heart disease is doubled in people with diabetes.

[ILLUSTRATION OMITTED]

Lipid lowering

Reduction of cardiovascular risk requires a multifactorial intervention, based on the results of several large intervention trials (e.g. Gaede et al, 2003). This should include aggressive lipid lowering with statins, aggressive blood pressure lowering based on inhibition of the renin-angiotensin system, and appropriate use of antiplatelet agents.

There is now convincing evidence that the use of statins is beneficial for primary and secondary prevention in diabetes (Collins et al, 2003; Sever et al, 2003; Colhoun et al, 2004). The exact age at which therapy should be started is not clear. Patients over 40 years of age were included in the studies; it is not clear if statin therapy should be started in younger patients. The possible role of fibrates should become clearer later this year when the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study results are published.

Blood pressure lowering

Both ramipril and perindopril have been shown to reduce cardiovascular events separate from a blood pressure-lowering effect (heart Outcomes Prevention Evaluation Study Investigators, 2000; Fox et al, 2003), and the use of these drugs should form the cornerstone of the treatment of hypertension in diabetes. Many patients, however, will require multiple agents to reach target blood pressure readings, and diuretics or calcium-channel blockers are a suitable addition. Beta-blockers should be reserved for patients not controlled with these other drugs, or for patients with symptomatic coronary heart disease.

Antiplatelet agents

In a meta-analysis (Antithrombotic Trialists' Collaboration, 2002), aspirin reduced events when used as secondary prevention in diabetes, but the benefit for primary prevention is unproven, and is the subject of a large trial being run through the clinical trials unit in Oxford.

Glycaemia

The control of glycaemia should initially be based on treatment with metformin, but newer drugs may have some advantages. In particular, the recent PROspective pioglitAzone Clinical Trial In macro Vascular Events (PROactive) trial demonstrated that pioglitazone 45 mg added to current cardiovascular therapies reduced deaths, myocardial infarctions and strokes in patients with type 2 diabetes and macrovascular disease, as described at the European Association for the Study of Diabetes 41st Annual Meeting (see page 154; www.proactive-results.com [accessed 23.09.2005]). The main side effects were oedema and an increase in hospitalisation for heart failure, but this was counterbalanced by a reduction in infarctions and strokes.

The best method of controlling glycaemia following acute myocardial infarction remains uncertain, and the Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 study has not clarified this issue (Malmberg et al, 2005). The immediate treatment should be with intravenous insulin, and thereafter treatment should be aimed at obtaining tight control of glycaemia using whatever glucose-lowering treatment is required.

Miles Fisher

Consultant Physician, Glagsow

Dr Fisher will be talking on cardiovascular risk and emerging therapies at the PCDS Conference at The Belfry, Warwickshire, 11-12 November 2005

Antithrombotic Trialists' Collaboration (2002) Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. British Medical Journal 324(7329): 71-86

Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ (2004) Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 364(9435): 685-96

Collins R, Armitage J, Parish S, Sleigh P, Peto R; Heart Protection Study Collaborative Group (2003) MRC/BHF heart protection study of cholesterol lowering with simvastatin in 5693 people with diabetes. A randomised placebo-controlled trial. Lancet 361(9374): 2005-16

Fox KM; EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators (2003) Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet 362(9386): 782-8

Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O (2003) Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. New England Journal of Medicine 348(5): 383-93

Heart Outcomes Prevention Evaluation Study Investigators (2000). Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet 355(9200): 253-9

Malmberg K, Ryden L, Wedel H, Birkeland K, Bootsma A, Dickstein K (2005) Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity. European Heart Journal 26(7): 650-1

Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M et al (2003) Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol levels in the Anglo-Scandanavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA). Lancet 361(9364): 1149-58

COPYRIGHT 2005 S.B. Communications
COPYRIGHT 2005 Gale Group