In Reply: We agree with Dr Crouse that differences
in study design and in the LDL-C levels between patients receiving treatment
and those not receiving treatment in the A to Z trial and the PROVE IT trial
may have contributed to differences in outcomes between the 2 studies. Because
cholesterol-lowering studies typically enroll patients with variable cholesterol
levels at entry and then treat patients with fixed dosages of study drug,
they are not well-suited to identify specific LDL-C level treatment goals.
On the other hand, the A to Z trial and the PROVE IT trial do suggest that
more aggressive LDL-C level lowering strategies reduce intermediate (2-year)
adverse event rates in patients with ACS and support, albeit indirectly, an
LDL-C level treatment goal substantially below 100 mg/dL (<2.59 mmol/L).
Further studies are needed before a specific LDL-C treatment goal of 70 mg/dL
(1.81 mmol/L) can be firmly established. Finally, no patients in the A to
Z trial met the stringent definition of rhabdomyolysis from the American College
of Cardiology, the American Heart Association, and the National Heart, Lung,
and Blood Institute, which requires concomitant renal failure in addition
to muscle symptoms and creatine phosphokinase elevation.
de Lemos JA, Blazing MA, Califf RM, Wiviott SD, Braunwald E. High-Dose Statins in Acute Coronary Syndromes—Reply. JAMA. 2005;293(1):36–39. doi:10.1001/jama.293.1.38-b
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