Secondary Prevention of Cardio-Vascular Disease

• NZ Guidelines Group

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• Overview

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• Treating to New Targets (TNT) trial
• Supports a lower LDL cholesterol target in stable coronary artery disease
• Comparison of the TNT trial with selected studies
• Apo B in TNT and IDEAL

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• PROVE IT
• Supports more intensive lipid lowering after acute coronary syndromes

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• Looking Beyond LDL
• Apolipoprotein-B and A1
  
  • Notes from ASEANZ 2009
  • Apo B in TNT and IDEAL
• HDL Cholesterol
• Non-HDL cholesterol Levels
• CRP in the PROVE IT trial

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• Diabetes
• New targets for management- notes from ASEANZ 2009
• Controversies- notes from ASEANZ 2009
• Macrovascular complications- more than just HbA1C- notes from ASEANZ 2009

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• Supplements
• Folic Acid

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• South Asians
  • Optimal Risk Factor Status for South Asians for Secondary Prevention
  • BMI measurement leads to underestimation of obesity

Lipid Modifying Therapy for Secondary Prevention

What is the Target LDL Cholesterol Level For Those With Stable Coronary Artery Disease?

The PROVE-IT study randomised patients after an acute coronary syndrome to intensive lipid lowering with atorvastatin vs treatment with pravastatin. This was one of studies that prompted a change in the USA's guidelines in 2004 to include an option of more intensive LDL lowering for secondary prevention.

The Treating to New Targets (TNT) study was recently published in the New England Journal of Medicine giving further support to the "lower is better" approach for secondary prevention.

TNT enrolled almost 18,500 participants (mean age approximately 61 years) with stable coronary artery disease that had a LDL cholesterol less than 130mg/dl (3.4 mmol/l) when treated with atorvastatin 10mg daily. The patients were randomised to atorvastation 10mg daily or 80mg daily.

The study's primary endpoint was the occurrence of a first major cardiovascular event, defined as death from CHD, nonfatal nonprocedural-related MI, resuscitation, or fatal or nonfatal stroke. After a mean follow-up of 4.9 years the study found:

• a 22% reduction in the primary endpoint for a 2.2% absolute reduction (10.9% vs 8.7%)
• no significant reduction in cardiovascular or all cause mortality. The trial was not large enough to investigate these endpoints in isolation presumably because the mortality rates were much lower than some of the earlier landmark trials such as 4S and LIPID.

An analysis of the individual components of the primary endpoint showed:

• coronary heart disease death reduced from 2.5% to 2.0% (NS)
• non-procedural non-fatal myocardial infarction reduced from 6.2% to 4.9%
• fatal and non-fatal stroke reduced from 3.1% to 2.3%
• similar rates of resuscitation from cardiac arrest in both groups- 0.5%

The mean LDL cholesterol level in the high dose atorvastatin group was 2.0 mmol/l compared with a level of 2.6 mmol/l in the low dose group. Many will regard the findings as supporting a lower LDL cholesterol target level for secondary prevention. However, the editorial that was published in the same issue of the New England Journal Of Medicine raised concerns about the non-significant increase in non-cardiovascular deaths in the high dose atorvastatin group.

However, quite clearly, the cost-benefit ratio will not be as favourable for using atorvastatin 80 mg daily vs atorvastatin 10 mg daily. For the sake of consistency, if we decide to treat all patients to a lower LDL cholesterol target, then we will also have to review our threshold for pharmacological therapy for primary prevention, we would have to regard the threshold suggested by the NZ guidelines as being too high.

Hitesh Patel, Cardiologist
23rd March, 2005

Reference:

• TNT investigators. Intensive Lipid Lowering with Atorvastatin in Patients with Stable Coronary Disease. N Engl J Med 2005;352.
• PROVE IT-TIMI 22 Investigators. Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes. N Engl J Med 2004;350:1495-504.