|
Clinical Question:
Is intensive lowering of serum lipids with statin drugs beneficial in
patients with stable coronary artery disease?
Bottom Line:
The intensive reduction of low-density lipoprotein (LDL) levels to well
below 100 mg/dL (2.5 mmol/L) did not result in a significant reduction in
the recurrence of major coronary events or all-cause mortality among
patients with stable coronary artery disease. Intensive lowering is
associated with an increased risk of discontinuing medication because of
adverse events and significant drug costs. Aiming for an LDL of
approximately 100 mg/dL (2.5 mmol/L) seems optimal for the majority of
patients with stable disease.
Reference:
Pedersen TR, Faergeman O, Kastelein JJ, et al, for the Incremental Decrease
in End Points Through Aggressive Lipid Lowering (IDEAL) Study Group.
High-dose atorvastatin vs usual-dose simvastatin for secondary prevention
after myocardial infarction. The IDEAL study: A randomized controlled trial.
JAMA 2005; 294:2437-45.
Study Design:
Randomized controlled trial (single-blinded)
Synopsis:
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. To compare the effects of 2
strategies of lipid lowering on the risk of cardiovascular disease among
patients with a previous myocardial infarction (MI). 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. 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). Occurrence of a major coronary event, defined as coronary death,
confirmed nonfatal acute MI, or cardiac arrest with resuscitation. 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. |