This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 113/11/1406    most recent CIRCULATIONAHA.105.586347v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wiviott, S. D. Articles by Braunwald, E. Search for Related Content PubMed PubMed Citation Articles by Wiviott, S. D. Articles by Braunwald, E. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ATORVASTATIN HEPTANOIC ACID L-TYROSINE PYRROLE Medline Plus Health Information Statins Related Collections Secondary prevention Risk Factors Acute coronary syndromes Related Article

(Circulation. 2006;113:1406-1414.)
© 2006 American Heart Association, Inc.

Coronary Heart Disease

A Tale of Two Trials

A Comparison of the Post–Acute Coronary Syndrome Lipid-Lowering Trials A to Z and PROVE IT–TIMI 22

Stephen D. Wiviott, MD; James A. de Lemos, MD; Christopher P. Cannon, MD; Michael Blazing, MD; Sabina A. Murphy, MPH; Carolyn H. McCabe, BS; Robert Califf, MD; Eugene Braunwald, MD

From the TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, The Department of Medicine, Harvard Medical School, Boston, Mass (S.D.W., C.P.C., S.A.M., C.M.C., E.B.); The Donald W. Reynolds Cardiovascular Clinical Research Center, University of Texas Southwestern Medical School, Dallas (J.A.d.L.); and the Duke Clinical Research Institute, Durham, NC (M.B., R.C.).

Correspondence to Stephen D. Wiviott, MD, The TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115. E-mail swiviott{at}partners.org

Received August 31, 2005; revision received December 23, 2005; accepted January 3, 2006.

Background— The Aggrastat to Zocor (A to Z) and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) trials compared intensive and moderate statin therapy after acute coronary syndromes, with seemingly disparate results. We analyzed the design, implementation, and results of the two trials in an attempt to clarify the effects of early intensive statin therapy.

Methods and Results— Study design, end points, and definitions were compared. In each trial, comparisons were made between intensive and moderate arms for both trials’ primary end points and death/myocardial infarction. Analyses were performed over various time points: at the end of the trials, 4 months, and >4 months. Subjects in A to Z had higher-risk demographics. More PROVE IT subjects were enrolled in the United States and underwent prerandomization revascularization. The low-density lipoprotein (LDL) difference was greater in A to Z than in PROVE IT early (4 months) but less late. Significant C-reactive protein reduction was earlier in PROVE IT. With common end points, event rates were higher in A to Z, and early favorable separation of event curves was seen in PROVE IT but not in A to Z. Clinical end point rates and reductions were similar in both trials after 4 months.

Conclusions— An early benefit was seen in PROVE IT but not in A to Z. Late-phase results were similar. Factors that may explain this disparity include the intensity of therapy in the early phase, timing, and magnitude of LDL and C-reactive protein lowering, differences in early revascularization, and the play of chance. Taken together, the results of these trials support a strategy of early intensive statin therapy coupled with revascularization when appropriate in patients after acute coronary syndrome.

---

 

CLINICAL PERSPECTIVE

Related Article:

Issue Highlights
Circulation 2006 113: 1377. [Extract] [Full Text]

This article has been cited by other articles:

				J. Afilalo, A. A Majdan, and M. J Eisenberg Intensive statin therapy in acute coronary syndromes and stable coronary heart disease: a comparative meta-analysis of randomised controlled trials Heart, August 1, 2007; 93(8): 914 - 921. [Abstract] [Full Text] [PDF]

				E. M. Tuzcu and S. J. Nicholls Statins: Targeting Inflammation by Lowering Low-Density Lipoprotein? J. Am. Coll. Cardiol., May 22, 2007; 49(20): 2010 - 2012. [Full Text] [PDF]

				P. S. Chan, B. K. Nallamothu, H. S. Gurm, R. A. Hayward, and S. Vijan Incremental Benefit and Cost-Effectiveness of High-Dose Statin Therapy in High-Risk Patients With Coronary Artery Disease Circulation, May 8, 2007; 115(18): 2398 - 2409. [Abstract] [Full Text] [PDF]

				C. P. Cannon, B. A. Steinberg, S. A. Murphy, J. L. Mega, and E. Braunwald Meta-Analysis of Cardiovascular Outcomes Trials Comparing Intensive Versus Moderate Statin Therapy J. Am. Coll. Cardiol., August 1, 2006; 48(3): 438 - 445. [Abstract] [Full Text] [PDF]

				R. P. Giugliano and E. Braunwald The Year in Non-ST-Segment Elevation Acute Coronary Syndromes J. Am. Coll. Cardiol., July 18, 2006; 48(2): 386 - 395. [Full Text] [PDF]

				B. G. Brown Direct Comparison of the A to Z and PROVE IT Trials: A Second Chance to Gain a First Impression Circulation, March 21, 2006; 113(11): 1382 - 1384. [Full Text] [PDF]