| Authors |
| Pedersen TR, Faergeman O, Kastelein JJ,et al. |
| Title |
| High-dose atorvastatin vs. usual-dose simvastatin for secondary prevention after myocardial infarction |
| References |
| JAMA. 2005 Nov 16;294(19):2437-45. |
| Background |
| Evidence suggests that more intensive lowering of low-density lipoprotein cholesterol (LDL-C) than is commonly applied clinically will provide further benefit in stable coronary artery disease. |
| Purpose |
| To determine if intensive lowering of LDL-C with atorvastatin at the highest recommended dose would yield incremental benefit compared with the moderate, most widely used dose of simvastatin among patients with a previous myocardial infarction. |
| Design |
- Multicenter, randomized, open label, blinded end-point
- 4439 patients (atorvastatin 80mg/day); 4449 patients (simvastatin 20mg/day)
- Age <80 years with history of MI and qualified for statin therapy as per national guidelines
|
| Exclusion Criteria |
- Hypersensitivity to statins
- Uncontrolled diabetes
- Hemodynamically significant valvular disease
- ALT >2x ULN
- Uncontrolled hypothyroidism
- Treatment with lipid lowering drugs
- Congestive heart failure (NYHA III/IV)
- Triglycerides >6.8mmol/L
- Nephrotic syndrome, alcohol abuse, therapy with immunosuppressants
|
| Follow-Up |
| Median 4.8 years |
| Treatment Regimen |
- Either atorvastatin 80 mg or simvastatin 20 mg per day
- Follow up visits 12, 24 weeks and every 6 months thereafter. Assessments included routine blood work and clinical interview
- If at 24 weeks total cholesterol >5.0 mmol/L, the dose of simvastatin doubled to 40 mg/day. The dose of atorvastatin could be decreased to 40 mg/day for adverse events
|
| Results |
|
Primary Endpoints
Simvastatin
n=4449 |
Atorvastatin
n=4439 |
Hazard Ratio |
p |
| Major CV event (cardiac death, non-fatal MI or resuscitation after cardiac arrest) |
| 10.4% |
9.3% |
0.89 (0.78-1.01) |
0.07 |
| Cardiac death |
| 4.0% |
3.9% |
0.99 (0.80-1.22) |
0.90 |
| Non-fatal MI |
| 7.2% |
6.0% |
0.83 (0.71-0.98) |
0.02 |
Mean LDL 2.7mmol/L (simvastatin); 2.1mmol/L (atorvastatin)
Secondary Outcomes
(see study for complete list)
Simvastatin
n=4449 |
Atorvastatin
n=4439 |
Hazard Ratio |
p |
| Major CV event |
| 13.7% |
12.0% |
0.87 (0.78-0.98) |
0.02 |
| Any CHD event |
| 23.8% |
20.2% |
0.84 (0.76-0.91) |
<0.001 |
| Any CV event |
| 30.8% |
26.5% |
0.84 (0.78-0.91) |
<0.001 |
- Major cardiovascular events (any primary event plus stroke)
- Any CHD event (any primary event, any coronary revascularization procedure, or hospitalization for unstable angina)
- Any cardiovascular events (any of the former plus hospitalization with congestive heart failure and peripheral arterial disease, defined as new clinical diagnosis or hospitalization for such disease)
|
| Summary |
- In patients with previous MI, intensive lowering of LDL-C did not result in a significant reduction in the primary outcome of major coronary events, but did reduce the risk of other composite secondary end points and nonfatal acute MI. There were no differences in cardiovascular or all-cause mortality.
- Patients with MI may benefit from intensive lowering of LDL-C without an increase in noncardio-vascular mortality or other serious adverse reactions.
|