Rationale for an early aldosterone blockade in acute myocardial infarction and design of the ALBATROSS trial Farzin Beygui, MD, PhD, a,f Eric Vicaut, MD, PhD, b,f Patrick Ecollan, MD, c,f Jacques Machecourt, MD, PhD, c,f Eric Van Belle, MD, PhD, d,f Faiez Zannad, MD, PhD, e,f and Gilles Montalescot, MD, PhD a,f Paris, France Background Aldosterone is at its highest levels at presentation for acute myocardial infarction (AMI). High aldosterone levels are predictive of poor outcome regardless of heart failure. Angiotensin-converting enzyme inhibitors have delayed partial and temporary effects on aldosterone levels. We hypothesize that aldosterone receptor blockade, early after AMI onset on top of standard therapy, may improve clinical outcome. Study Design ALBATROSS is a nationwide, multicenter, open-labeled, randomized trial designed to assess the superiority of aldosterone blockade by a 200-mg intravenous bolus of potassium canrenoate followed by a daily 25-mg dose of spirinolactone for 6 months, on top of standard therapy compared to standard therapy alone among 1,600 patients admitted for ST-segment elevation or high risk non–ST-segment elevation acute AMI -TIMI score ≥3—within 72 hours after symptom onset regardless of heart failure and treatment strategy. The primary efficacy end point of the study is the 6-month rate of the composite of death, resuscitated cardiac arrest, significant ventricular arrhythmia, class IA American College of Cardiology/American Heart Association/European Society of Cardiology indication for implantable cardioverter device, and new or worsening heart failure. Secondary end points include each of the components of the primary end point, different combinations of such components, the primary end point assessed at hospital discharge and 30-day follow-up, and rates of acute renal failure. Safety end points include rates of hyperkalemia and premature drug discontinuation. Conclusions ALBATROSS will assess the cardiovascular benefit of a low-cost aldosterone receptor blocker on top of standard therapy in all-coming AMI patients. (Am Heart J 2010;160:642-648.e1.) Rationale Acute myocardial infarction (AMI) and its subsequent hemodynamic changes lead to complex neurohormonal activation. 1-3 The renin-angiotensin-aldosterone pathway is one corner stone of such neurohormonal activation. The blockade of angiotensin-converting enzyme (ACE) by ACE inhibitors has been widely demonstrated to be associated with a reduction in mortality after myocardial infarction. 4 Aldosterone is at its highest levels at presentation after AMI and ACE inhibitors effect on plasma aldosterone levels in a delayed, partial and temporary fashion. 1-3 Aldosterone, the final mediator of the renin-angioten- sin-aldosterone pathway, is reported to promote a broad spectrum of deleterious cardiovascular effects including acute endothelial dysfunction, 5 inhibition of NO activi- ty, 6 increased endothelial oxidative stress, 7 increased vascular tone, 8 inhibition of tissue recapture of catecho- lamines, 9 rapid occurrence of vascular smooth muscle cell and cardiac myocyte necrosis, 10,11 collagen deposi- tion in blood vessels, 12 myocardial hypertrophy, and fibrosis. 13-15 Moreover, the primary epithelial actions of aldosterone lead to Na + retention and to potentially arrhythmogenic K + and Mg ++ depletion. 9 Three recently published studies of independent cohorts have concordantly shown that high aldosterone From the a Institut de Cardiologie and INSERM U937, Centre Hospitalier Universitaire Pitié- Salpêtrière, Paris, France, b Centre Hospitalier Universitaire F. Widal-Lariboisère, Paris, France, c Centre Hospitalier Universitaire de Grenoble, France, d Centre Hospitalier Universitaire de Lille, France, and e Centre Hospitalier Universitaire de Nancy, France. f on behalf of the ALBATROSS Investigators. See online Appendix for complete listing. ALBATROSS: Aldosterone Lethal effects Blocked in Acute myocardial infarction Treated with or without Reperfusion to improve Outcome and Survival at Six months follow-up (clinicaltrials.gov registration number NCT 01059136). Submitted April 19, 2010; accepted June 28, 2010. Reprint requests: Gilles Montalescot, MD, PhD, Institut de Cardiologie, Bureau 236, Centre Hospitalier Universitaire Pitié-Salpêtrière, AP-HP, 47 Blvd de l'Hôpital, 75013 Paris, France. E-mails: gilles.montalescot@psl.aphp.fr, sissel.paulsrud@psl.aphp.fr 0002-8703/$ - see front matter © 2010, Mosby, Inc. All rights reserved. doi:10.1016/j.ahj.2010.06.049