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

PROVE IT- More Intensive LDL Lowering is Beneficial after Acute Coronary Syndromes

The PROVE IT trial enrolled over four thousand patients within ten days of hospitalisation for an acute coronary event. The patients were randomised to 40 mg of pravastatin daily or to 80 mg of atorvastatin daily (intensive therapy). Median LDL cholesterol levels prior to treatment were 2.7 mmol/l.

The primary end point was a composite of:

• death from any cause
• myocardial infarction
• documented unstable angina requiring rehospitalization, and
• need for revascularisation after thirty days from enrollment.

Mean follow-up was for 24 months. The median LDL cholesterol level achieved during treatment was 2.46 mmol per liter in the pravastatin group and 1.6mmol/l in the high-dose atorvastatin group (P<.001).

The estimated two year event rates were reduced by 16 percent by intensive therapy, from 26.3 percent in the pravastatin group to 22.4 percent in the atorvastatin group. In other words, only about 25 patients need to be treated for two years to prevent one event.

Sub-group analysis should always be viewed with caution but interestingly showed no significant benefit with more intensive therapy in the group with LDL cholesterol levels less than 3.2 mmol/l prior to randomisation or in those who had prior treatment with statins. These issues may be worth considering if one has to advise a patient to consider purchasing atorvasatin to lower LDL cholesterol levels much more intensively, and as done in this trial.

Whether other markers will aid the selection of patients for more intensive therapy is also an area of debate. Potential markers that might be used include apo-B, highly sensitive CRP levels, and soluble CD40 ligand. A further analysis of the PROVE-IT trial suggests that those patients that attained the dual goals of LDLC <70mg/dl (1.8mmol/l) and hs-CRP<2mg/d had the best outcome. Those patients treated with high dose atorvastatin were more likely to attain the hs-CRP target. Ideally, there will be prospective validation of this finding and a better definition of the threshold of CRP that should be regarded as justifying more intensive therapy.

• PROVE IT-TIMI 22 Investigators. Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes. N Engl J Med 2004;350:1495-504.
• PROVE IT-TIMI 22 Investigators. C-Reactive Protein Levels and Outcomes after Statin Therapy. N Engl J Med 2005;352:20-8.