To the Editor: The article by Dr de Lemos et al1 reporting the results of phase Z of the A to Z trial and the accompanying editorial by Dr Nissen2 provide important new information about event reduction by statins. Differences between conclusions of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL)3 and the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT)4 trials may be due to differences in trial design.
In contrast to the PROVE IT trial and the A to Z trial, MIRACL compared statin treatment with placebo, rather than an active comparator or different dose of statin treatment, and MIRACL relied on soft end points. The PROVE IT trial and the A to Z trial differed in the acuteness of the intervention setting, the magnitude of the difference in low-density lipoprotein cholesterol (LDL-C) levels among patients in the 2 treatment groups, and the LDL-C levels in the less aggressively treated group. The PROVE IT trial has been used to justify an LDL-C level of 70 mg/dL (1.81 mmol/L) for high-risk individuals.5 However, in the PROVE IT trial, only half of the participants taking pravastatin achieved an LDL-C level lower than 100 mg/dL (<2.59 mmol/L), and there was no difference in events between the aggressively and less aggressively treated groups for the subset with LDL-C levels at baseline lower than 125 mg/dL (<3.24 mmol/L), a subgroup in which pravastatin would likely achieve an LDL-C level lower than 100 mg/dL (<2.59 mmol/L). In the low-dose group in the A to Z trial, the 25th percentile LDL-C level was 66 mg/dL (1.71 mmol/L) and the 75th percentile was 96 mg/dL (2.49 mmol/L), suggesting that this group achieved its LDL-C level goal.
Additionally, the clinical advisory board of the American College of Cardiology, the American Heart Association, and the National Heart, Lung, and Blood Institute6 defines rhabdomyolysis as an elevation in creatine phosphokinase with myalgia and evidence of renal failure. It would be of interest to know how many patients in the A to Z trial fulfilled this renal failure criterion for rhabdomyolysis.
Financial Disclosure: Dr Crouse has received honoraria for speaking engagements from Bristol-Myers Squibb, Kos Pharmaceuticals, Abbott, Merck-Schering-Plough, Parke-Davis, Pfizer, Bayer, Sankyo Pharmaceuticals, AstraZeneca, and Otsuka Pharmaceuticals; has received grant support from Bristol-Myers Squibb, Kos Pharmaceuticals, Merck, Merck-Schering-Plough, AstraZeneca, Bayer, Sankyo Pharmaceuticals, Pfizer, and Otsuka Pharmaceuticals; has served on advisory boards for Merck, Merck-Schering-Plough, Pfizer, Kos Pharmaceuticals, AstraZeneca, and Andrx Pharmaceuticals; and receives a partial salary from AstraZeneca as primary investigator of the METEOR trial.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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