| Authors |
| Armitage J, Bowman L, Wallendszus K, et al. |
| Title |
| Intensive lowering of LDL cholesterol with 80 mg vs. 20 mg simvastatin daily in 12,064 survivors of myocardial infarction |
| References |
| Lancet. 2010 Nov 13;376(9753):1658-69 |
| Background |
| Lowering of LDL cholesterol reduces major vascular events, but whether more intensive therapy safely produces extra benefits is uncertain. |
| Purpose |
| To help establish reliably the balance of efficacy and safety of more intensive LDL-cholesterol-lowering therapy by comparing long-term treatment with 80 mg vs. 20 mg simvastatin daily in a large population of patients at high risk of cardiovascular events. |
| Design |
- Multicenter, randomized, double blind study
- 12,064 patients
- Age 18-80 years with history of MI and qualified for statin therapy as per national guidelines
- Total cholesterol >3.5 mmol/L if already on statin; 4.5 mmol/L if not on statin already
|
| Exclusion Criteria |
- Hypersensitivity to statins
- Severe renal disease (Cr >2x ULN)
- CK >3x ULN
- ALT >1.5x ULN
- Therapy with immunosuppressants
|
| Follow-Up |
| Median 6.7 years |
| Treatment Regimen |
- Either simvastatin 80 mg or 20 mg per day
- Follow up visits 2, 4, 8 and 12 months after randomization and every 6 months thereafter. Assessments included routine blood work and clinical interview
|
| Results |
|
Primary Endpoints
Simvastatin 80 mg
n=6031 |
Simvastatin 20 mg
n=6033 |
Hazard Ratio |
p |
| Major vascular event (cardiac death, non-fatal MI, any stroke or revascularization) |
| 24.5% |
25.7% |
0.94 (0.88-1.01) |
0.10 |
Simvastatin 80 mg produced an average 0.35 (SE 0.01) mmol/L greater reduction in LDL cholesterol compared with allocation to 20 mg
Secondary Outcomes
(see study for complete list)
There were no apparent differences in numbers of haemorrhagic strokes (24 [0.4%] vs. 25 [0.4%]) or deaths attributed to vascular (565 [9ยท4%] vs. 572 [9.5%]) or non-vascular (399 [6.6%] vs. 398 [6.6%]) causes.
Compared with two (0.03%) cases of myopathy in patients taking 20 mg simvastatin daily, there were 53 (0.9%) cases in the 80 mg group.
|
| Summary |
- The 6% (SE 3.5%) reduction in major vascular events with a further 0.35 mmol/L reduction in LDLcholesterol in this trial is consistent with previous trials.
- There is limited clinical benefit from the increased dose of simvastatin with an increase in myopathy at the higher dose. Intensive lowering of LDL cholesterol can be achieved safely with other pharmacologic regimens.
|