"Mortality and Morbidity in Patients with Stable Coronary Heart Disease and LDL Cholesterol Levels".The New England Journal of Medicine. 2005.

Contents

1. Clinical Question
2. Bottom Line
3. Major Points
4. Guidelines
5. Design
6. Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7. Interventions
8. Outcomes
8.1 Primary Outcomes
8.2 Secondary Outcomes
9. Funding
10. Further Reading

Clinical Question

Does intensive lipid-lowering therapy with 80 mg of atorvastatin per day provide additional clinical benefit for patients with stable coronary heart disease (CHD) compared to 10 mg of atorvastatin per day when LDL cholesterol is already below 130 mg/dL?

Bottom Line

Intensive lipid-lowering therapy with 80 mg of atorvastatin per day in patients with stable CHD resulted in significant reductions in major cardiovascular events compared to treatment with 10 mg of atorvastatin per day, despite a greater incidence of elevated aminotransferase levels.

Major Points

Guidelines

As of the last knowledge update, guidelines recommend targeting lower levels of LDL cholesterol for secondary prevention in patients with a high risk of cardiovascular events.

Design

- Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial.
- N=10,001 patients with clinically evident CHD and LDL cholesterol <130 mg/dL.
- Intervention: 80 mg atorvastatin per day (n=4995) or 10 mg atorvastatin per day (n=5006).
- Setting: 14 countries.
- Enrollment: 1998-1999.
- Mean follow-up: 4.9 years.
- Primary outcome: Major cardiovascular event (CHD death, nonfatal myocardial infarction, resuscitation after cardiac arrest, fatal or nonfatal stroke).

Population

Inclusion Criteria
- Men and women aged 35-75 years with clinically evident CHD.
- Baseline LDL cholesterol between 130-250 mg/dL.
- Triglyceride levels ≤600 mg/dL.

Exclusion Criteria
- Patients with triglyceride levels >600 mg/dL or other exclusionary conditions.
- Patients did not tolerate initial 10 mg atorvastatin in run-in phase.

Baseline Characteristics
- Participants had a history of previous myocardial infarction, angina with evidence of CHD, or coronary revascularization.
- Demographics were well matched between groups at baseline.

Interventions

- Discontinuation of previous lipid-regulating drugs followed by an atorvastatin 10 mg run-in phase.
- Randomization to double-blind therapy with either 10 mg or 80 mg atorvastatin daily.

Outcomes

Primary Outcome
- 8.7% patients in the 80 mg group experienced a primary event compared to 10.9% in the 10 mg group, resulting in an absolute event rate reduction of 2.2% and relative risk reduction of 22% (hazard ratio = 0.78; P<0.001).

Secondary Outcomes
- Significant reductions in risk for major coronary events, cerebrovascular events, and hospitalization for congestive heart failure noted in the 80 mg group.

Funding

The study was funded by Pfizer.

Further Reading

The full trial publication is available at the New England Journal of Medicine: [link]