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IDEAL: The IDEAL: The IIncremental ncremental DDecrease in ecrease in EEnd Points nd Points

Through Through AAggressive ggressive LLipid ipid Lowering StudyLowering Study

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IDEAL: Study design

Objective: To compare intensive vs less-intensive lipid-lowering therapies

Design: Prospective, randomized, open-label, blinded end-point evaluation ( PROBE)

Population: N = 8888 with previous MI

Treatment: Atorvastatin 80 mg, simvastatin 20-40 mg/d

Primary outcome: Coronary death, nonfatal MI, resuscitated cardiac arrest

Secondary outcomes: Major CVD (primary event, stroke), CHD (primary event,

coronary revascularization, hospitalization for UA), any CVD (any of the above, PAD, hospitalization for CHF), all-cause mortality

Follow-up: Median 4.8 years

Pedersen TR et al. JAMA. 2005;294:2437-45.

Incremental Decrease in End Points Through Aggressive Lipid Lowering

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IDEAL: Reduction in primary endpoint

Pedersen TR et al. JAMA. 2005;294:2437-45.

Cumulativehazard (%)

Major coronary event*

Time from randomization (years)No. at risk

Simvastatin 4449 4293 4165 4037 3917 1200Atorvastatin 4439 4285 4170 4053 3940 1182

16

12

8

4

01 2 3 4 50

Simvastatin

Atorvastatin

11% RRRHR = 0.89 (95% CI, 0.78–1.01) P = 0.07

*Death from CAD, nonfatal MI, cardiac arrest with resuscitation

Incremental Decrease in End Points Through Aggressive Lipid Lowering

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IDEAL: Reduction in secondary endpoints

Pedersen TR et al. JAMA. 2005;294:2437-45.

Cumulativehazard (%)

Any coronary heart disease*

Time from randomization (years)

No. at riskSimvastatin 4449 3937 3920 3527 3370 1002Atorvastatin 4439 3984 3799 3632 3496 1032

40

30

20

10

0

1 2 3 4 50

Any cardiovascular disease†

Time from randomization (years)

4449 3841 3580 3338 3127 9084439 3902 3671 3469 3299 963

40

30

20

10

0

1 2 3 4 50

Simvastatin

Atorvastatin

Simvastatin

Atorvastatin

*Major coronary event, hospitalization for UA, coronary revascularizations†CHD endpoints, peripheral vascular disease, hospitalization for nonfatal CHF

Incremental Decrease in End Points Through Aggressive Lipid Lowering

16% RRRHR = 0.84 (95% CI, 0.76–0.91) P < 0.001

16% RRRHR = 0.84 (95% CI, 0.78–0.91) P < 0.001

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IDEAL: Summary

High-dose atorvastatin vs usual-dose simvastatin in post-MI patients:

• Trend to benefit in primary outcome (11% RRR)

• Significant reductions in composite secondary outcomes (13% to 16%)

• No difference between groups in all-cause or CV mortality

• No difference between groups in serious adverse events

– Incidence of liver enzyme elevation with atorvastatin was <1% and comparable with results of other trials

4 studies now support aggressive lipid lowering to reduce CV events in high-risk patients:

IDEAL, PROVE IT-TIMI 22, A to Z, TNT

Pedersen TR et al. JAMA. 2005;294:2437-45.Cannon CP. JAMA. 2005;294:2492-4.

Incremental Decrease in End Points Through Aggressive Lipid Lowering