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CLINICAL RESEARCH: ACUTE CORONARY SYNDROME

The Effect of Valsartan, Captopril, or Both on Atherosclerotic Events After Acute Myocardial Infarction

An Analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT)

John McMurray, MD, FACC^_*,_*, Scott Solomon, MD, FACC, Karen Pieper, MS, Shelby Reed, PhD, Jean Rouleau, MD, FACC, Eric Velazquez, MD, Harvey White, DSc, FACC^||, Jonathan Howlett, MD^¶, Karl Swedberg, MD, PhD^#, Aldo Maggioni, MD^_**, Lars Køber, MD, PhD, Frans Van de Werf, MD, FACC, Rob Califf, MD, FACC and Marc Pfeffer, MD, PhD, FACC

^_* Department of Cardiology, Western Infirmary, Glasgow, Scotland
Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts
Duke University Medical Center, Durham, North Carolina
The Montreal Heart Institute, Montreal, Canada
^|| Department of Cardiology, Green Lane Hospital, Auckland, New Zealand
^¶ QE 11 Heart Function and Transplantation Clinic, Dalhousie University, Halifax, Nova Scotia, Canada
^# Department of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden
^_** ANMCO Research Center, Florence, Italy
Department of Cardiology University of Copenhagen, Copenhagen, Denmark
Leuven Coordinating Center, Leuven, Belgium

Manuscript received June 22, 2005; revised manuscript received August 22, 2005, accepted September 8, 2005.

^_* Reprint requests and correspondence: Prof. John McMurray, Department of Cardiology, Level 4, Western Infirmary, Glasgow, G11 6NT, Scotland, United Kingdom. (Email: j.mcmurray{at}bio.gla.ac.uk).

OBJECTIVES: We attempted to compare the effect of an angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) on atherosclerotic events.

BACKGROUND: Angiotensin-converting enzyme inhibitors and ARBs interrupt the renin-angiotensin system by distinct mechanisms. It is not clear whether ARBs reduce atherosclerotic events such as myocardial infarction (MI) like ACE inhibitors. This evidence gap may reflect the nature of the studies conducted, to date. Placebo-controlled studies enrolled cohorts at low risk of atherosclerotic events (e.g., patients with chronic heart failure, most treated with an ACE inhibitor). One of the main active controlled trials was confounded by a blood pressure difference between treatments.

METHODS: We compared the effects of captopril, valsartan, and their combination on atherosclerotic events in 14,703 patients randomized in the Valsartan in Acute Myocardial Infarction Trial (VALIANT).

RESULTS: The number of individuals adjudicated as having a fatal or non-fatal MI in the captopril group was 559 (total investigator reported events 798), 587 (796) in the valsartan group, and 554 (756) in the combination group; valsartan versus captopril, p = 0.651 (0.965); combination versus captopril, p = 0.187 (0.350). Overall, all atherosclerotic events examined occurred at a similar frequency in the captopril and valsartan groups.

CONCLUSIONS: Angiotensin receptor blockers appear to be as effective as ACE inhibitors in reducing atherosclerotic events, even when used in addition to other secondary preventive treatments. These data, although not conclusive, also support the hypothesis that adding an ARB to an ACE inhibitor may have a small additional anti-infarction effect, a possibility that needs to be prospectively tested.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   ARB = angiotensin receptor blocker   CEC = Clinical End Points Committee   CHF = chronic heart failure   MI = myocardial infarction   ONTARGET = ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint trial   RAAS = renin-angiotensin system   SAVE = Survival And Ventricular Enlargement study   VALIANT = Valsartan in Acute Myocardial Infarction Trial   VALUE = Valsartan Antihypertensive Long-term Use Evaluation trial

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