High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL
Terje R Pedersen1, Ole Faergeman, John J P Kastelein
1Centre for Preventive Medicine, Ullevål University Hospital, Oslo, Norway. t.r.pedersen@medisin.uio.no
Insights
Intensive low-density lipoprotein cholesterol (LDL-C) lowering with high-dose atorvastatin did not significantly reduce major coronary events in patients with previous myocardial infarction (MI). However, it did lower the risk of nonfatal MI and other composite secondary endpoints without increasing mortality.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Evidence suggests intensive low-density lipoprotein cholesterol (LDL-C) lowering offers benefits in stable coronary artery disease.
- The optimal LDL-C reduction threshold for patients with established coronary artery disease remains under investigation.
Purpose of the Study:
- To compare the efficacy of high-dose atorvastatin versus usual-dose simvastatin in reducing cardiovascular events in patients with a history of myocardial infarction (MI).
Main Methods:
- The IDEAL study was a prospective, randomized, open-label trial involving 8888 patients with a history of MI.
- Patients received either high-dose atorvastatin (80 mg/d) or usual-dose simvastatin (20 mg/d) with a median follow-up of 4.8 years.
Main Results:
- Mean LDL-C levels were lower in the atorvastatin group (81 mg/dL) compared to the simvastatin group (104 mg/dL).
- A major coronary event occurred in 9.3% of atorvastatin patients versus 10.4% of simvastatin patients (HR, 0.89; P = .07).
- Nonfatal MI (6.0% vs 7.2%; P = .02) and major cardiovascular events (P = .02) were significantly reduced in the atorvastatin group. No differences in cardiovascular or all-cause mortality were observed.
Conclusions:
- Intensive LDL-C lowering with high-dose atorvastatin did not significantly reduce major coronary events but did reduce nonfatal MI and other composite secondary endpoints in patients with previous MI.
- This strategy was associated with increased transaminase elevations but no increase in cardiovascular or all-cause mortality or serious adverse events like myopathy.
Context:
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.
Objective:
To compare the effects of 2 strategies of lipid lowering on the risk of cardiovascular disease among patients with a previous myocardial infarction (MI).
Design, Setting, And Participants:
The IDEAL study, a prospective, randomized, open-label, blinded end-point evaluation trial conducted at 190 ambulatory cardiology care and specialist practices in northern Europe between March 1999 and March 2005 with a median follow-up of 4.8 years, which enrolled 8888 patients aged 80 years or younger with a history of acute MI.
Interventions:
Patients were randomly assigned to receive a high dose of atorvastatin (80 mg/d; n = 4439), or usual-dose simvastatin (20 mg/d; n = 4449).
Main Outcome Measure:
Occurrence of a major coronary event, defined as coronary death, confirmed nonfatal acute MI, or cardiac arrest with resuscitation.
Results:
During treatment, mean LDL-C levels were 104 (SE, 0.3) mg/dL in the simvastatin group and 81 (SE, 0.3) mg/dL in the atorvastatin group. A major coronary event occurred in 463 simvastatin patients (10.4%) and in 411 atorvastatin patients (9.3%) (hazard ratio [HR], 0.89; 95% CI, 0.78-1.01; P = .07). Nonfatal acute MI occurred in 321 (7.2%) and 267 (6.0%) in the 2 groups (HR, 0.83; 95% CI, 0.71-0.98; P = .02), but no differences were seen in the 2 other components of the primary end point. Major cardiovascular events occurred in 608 and 533 in the 2 groups, respectively (HR, 0.87; 95% CI, 0.77-0.98; P = .02). Occurrence of any coronary event was reported in 1059 simvastatin and 898 atorvastatin patients (HR, 0.84; 95% CI, 0.76-0.91; P<.001). Noncardiovascular death occurred in 156 (3.5%) and 143 (3.2%) in the 2 groups (HR, 0.92; 95% CI, 0.73-1.15; P = .47). Death from any cause occurred in 374 (8.4%) in the simvastatin group and 366 (8.2%) in the atorvastatin group (HR, 0.98; 95% CI, 0.85-1.13; P = .81). Patients in the atorvastatin group had higher rates of drug discontinuation due to nonserious adverse events; transaminase elevation resulted in 43 (1.0%) vs 5 (0.1%) withdrawals (P<.001). Serious myopathy and rhabdomyolysis were rare in both groups.
Conclusions:
In this study of 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 noncardiovascular mortality or other serious adverse reactions.Trial Registration ClinicalTrials.gov Identifier: NCT00159835.
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