Home > Information for doctors >Tutorials > Lipids and Cardiovascular Disease.
Francisco Machado 1997
Benefits of Lipid Lowering
| Lipids and secondary prevention of IHD |
| Lipids and primary prevention of IHD |
Lipids and secondary prevention of IHD
Lowering serum lipid concentrations in patients with IHD has been known to reduce the subsequent death from CVD for a number of years but there was concern that the all cause mortality was unchanged as deaths from cancer and violent deaths were increased. This led to alot of confusion until recently with the publication of the two trials reviewed below.
Scandinavian Simvastatin Survival Study (1)
4444 patients aged 35-70 (male and female) with a history of angina or acute
myocardial infarction. Exclusions were patients with AF, CCF, unstable angina
and those who had an MI within 6 months.
Patients with a fasting cholesterol between 5.5-8.0 mmol/l were randomized to receive simvastatin or placebo. Dose was increased to achieve a CE of <5.2 mmol/l. Patients continued on therapy and mean follow up was 5.4 yr. The trial was stopped early as there was a statistical difference between the two groups.
Results
Total mortality was decreased significantly in the treated group (8% vs. 12%), CVD deaths were decreased in the simvastatin group whilst there no increase in deaths from other causes particularly violent deaths. Simvastatin also reduced the incidence of a further AMI, angioplasty or CABG. Subgroup analysis showed that the effect was true for older patients. For women there was a reduction in CVS deaths but not all cause deaths, but this may have been due to low numbers.
The benefit of lipid lowering is incremental, i.e. patients already on aspirin and beta-blockers have additional benefit from simvastatin.
The significant benefit to patients did not occur for the first several years of therapy, which emphasizes the importance of continued treatment.
Cholesterol and Recurrent Events (CARE) Study (2)
Investigated whether lowering CE in survivors of MI with a "normal" CE
(<6.2mmol/l) would reduce the risk of a coronary event.
Over 4000 patients (86% men) aged 21- 75 were randomised to treatment for 5 years with either pravastatin 40mg or placebo.
the higher the pre- treatment LDL CE the greater the benefit, but with LDL < 3.2 there was no benefit found which might suggest that there is a threshold at which lipid lowering therapy is not effective in the prevention of CHD.
Long Term Intervention In Ischaemic Disease. LIPID study
(preliminary findings presented to the AHA meeting in 1997.
· 9,000 patients, either post MI or hospitalized with unsatble angina
· male and female, all age groups
· with average cholesterol (4-7mmol/l) and Tgs <5mmol/l
· randomly allocated to receive 40mg pravastatin or placebo
· mean follow up of 6 years
Trial was stopped prematurely
Main findings were:
· significant reductions in:
1. CHD death: RR reduction 24%
2. Fatal/non fatal MI: RR reduction 29%
3. CABG: RR reduction 24%
4. Total mortality RR reduction 23%
· benefit across all subgroups
The cost effectiveness of expensive drugs, such as statins, depends on the risk of IHD. A cost effective study based on the 4S study estimated that simvastatin treatment of men aged 55-64 who suffered a MI would cost £6000 per life year saved, whereas it would cost £361 000 life year saved for women aged 45-54 with angina.
Lipids and primary prevention of IHD
West of Scotland Coronary Prevention Study (WOSCOPS) (3)
6500 men, aged 45-64 years with a plasma total cholesterol > 6.5 mmol/land LDL 4.5 - 6 mmol/l, were randomised either to pravastatin 40mg od or to placebo for an average of 5 years.
Pravastatin:
The results suggest that treatment of 1000 such patients for 5 years would prevent 7 deaths and 20 non fatal MIs.
Sheffield Tables (4)
Identify patients who should have their cholesterol measured and who are likely to benefit from treatment. Risk factors for IHD such as hypertension, smoking, diabetes and LV hypertrophy are plotted against age in males and females, and a threshold for treatment is given.
Limitations:
I used must regularly review patients as their risk increases with age.
Other tables have been developed
Refs
1.Scandinavian Simvastatin Survival Study (4S) Lancet 1994; 344: 1383-89
2.Sacks et al. The effect of pravastatin on coronary events after myocardial
infarction in patients with average cholesterol levels. NEJM 1996;335 1001-9
3.Shepherd et al WOSCOPS: Prevention of coronary heart disease with pravistatin
in men with hypercholesterolaemia. NEJM 1995;333:1301-7
4.Ramsay et al Targeting lipid lowering drug therapy for primary prevention of
CHD: an updated Sheffield table. Lancet 1996;348:387-8
| [Top of page] |