Hyperlipidaemia

Footnotes

1. Evidence is for patients < 70 years. Discretion for patients> 70 years.
2. The recent SMAC advice on use of statins distinguishes between a level for patients post MI (4.8mmolll) and for other symptomatic CHD (5.5mmolll). We have chosen a level for all secondary prevention of 5.0 mmol/l aiming to include more patients in a regime for secondary prevention and for ease of use.
3. Great care in initiating thyroxine in hypothyroid patients. Use small initial dose and careful titration to avoid exacerbation of ischaemia.
4. Consider referral to dietician.
5. This guideline is equally applicable for patients with non-coronary atherosclerotic disease.

Explanatory text on guidelines for the management of serum cholesterol

By mid 1994 a number of secondary prevention trials using HMG-CoA reductase inhibitors in post AMI patients had been published. In general these studies showed that for each 10% reduction in cholesterol a 20% reduction in morbidity and mortality is obtained. The same was shown by the older "non-statin ¹⁰ trials. The Scandinavian Simvastatin Survival Study (4S) trial was the first single trial to show that cholesterol reduction in post AMI patients will reduce morbidity and mortality (including total mortality).

"4S" Study (1)

Brief synopsis of "45" trial

• Males and females, 35 - 70 years (average 60 years) 80% had previous AMI and the other 20% angina.
• Initial total cholesterol >5.5 mmol/L, randomised to simvastatin 20 mg od po, or placebo.
• After a follow up of 5.4 years, total cholesterol was reduced by 25% and total mortality reduced by 30%.
• In addition, major coronary events (defined as coronary death or any non-fatal AMI or resuscitation from cardiac arrest) were reduced by 34%.
• The risk of developing unstable angina, need for revascularisation, having a TIA or CVA were also reduced by about 30%.
• There were no increases in deaths from suicide, cancer or accidents. 6% withdrew from therapy in both treatment and placebo groups (presumed side effects).

"Care" Trial (2)

The CARE study progressed understanding by addressing the issue of secondary prevention as it applies to the majority of patients with average (not high) cholesterol values.

Brief synopsis of "CARE" study

• Survivors of acute MI with total cholesterol, 6.2 (and LDL 3.0-4.5).
• Pravastatin 4Omg od po versus placebo.
• 4159 males and females whose cholesterol levels were similar to the general population (the high and low cholesterol patients were removed from the study).
• A 20% reduction in total cholesterol occurred.
• A significant reduction (p=0.002) in CAD fatality and non-fatal MI were observed over five years.
• There was also a significant reduction in PTCA and CABG rates in treated group, and a significant reduction in CVA.

"ASPIRE" study (3)

Brief synopsis of ASPIRE study:

• The objective was to measure the potential for secondary prevention in CAD in the UK (which was found to be considerable).
• 2583 CAD patients surveyed. Found very poor rates of success in secondary prevention. For example >75% had cholesterol >5.2 at follow-up, up to 27% still smoked, 75% remained overweight, up to 25% remained hypertensive, only 30% were on a beta blocker, and up to 20% were not on aspirin.

Comments

• The guidelines for the management of serum cholesterol presented here are straightforward. Patients with known coronary disease are targeted.
• Measures to reduce total cholesterol to less than 5.Ommol/L are mandatory in every patient with coronary disease.

References

1. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with curonary heart disease. Lancet 1994, 344, 1383 - 9.
2. Frank M et al. The Effect of Pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. New Eng J Med 1996, 335, 1001-1009.
3. A British Cardiac Society survey of the potential for the secondary prevention of coronary disease: ASPIRE (Action on secondary prevention through intervention to reduce events) principal results. ASPIRE Steering Group. Heart 1996, 75 (4), 334 - 342.

Bradley Cheek 1999