All concepts, explanations, trials, and studies have been re-written in plain English and may contain errors. I am not a doctor ----------------------------------------------------------- NOTE: You can make the print bigger with the font button on your browser! (It's usually a big "A") ----------------------------------------------------------- 2002 Trial Results ------------------ AFFIRM This trial studied whether restoring and maintaining normal heart rhythm improved all-cause mortality versus using blood thinners and heart rate control in a-fib patients. A-fib patients have almost twice the usual risk of death. After screening 7400 patients, enrollment was stopped at just over 4000. The main underlying disorders were high blood pressure (51%), followed by coronary artery disease (26%). Only a very small number of patients had heart failure. The main study drugs were sotalol and amiodarone (for rhythm control), although quinidine was used early in the study. In the rate control group, ventricular rate control was done with digoxin, beta-blockers, and calcium-channel blockers (CCBs). In the rhythm control group, at least 80% were stabilized into normal heart rhythm and 60% remained in normal rhythm after 5 years. On the other hand, more patients in the rhythm control group were hospitalized. All-cause mortality was also slightly higher in the rhythm control group. Does this mean that in a-fib patients, restoring and maintaining normal heart rhythm may be somehow dangerous for the patient? Since it is unlikely that normal heart rhythm itself is harmful, perhaps the higher mortality rate is from a method used to achieve normal rhythm or a method for maintaining normal rhythm. Again, very few heart failure patients were in AFFIRM. ============================================ MADIT II The first MADIT was a relatively small trial (196 patients) that identified high-risk heart attack patients by the presence of nonsustained ventricular tachycardia (NSVT) and an EF less than 36%. Patients were further risk-identified by whether sustained VT (induced) was still inducible after procainamide was given. These patients then got either an ICD or an anti- arrhythmic drug, usually amiodarone. Close to 30% were not on drug therapy by the end of the study and there was a large imbalance in the patients on beta-blockers (7% in the drug group versus 27% in the ICD group). When the trial was stopped, total mortality in the ICD group was 53% less than that in the drug group. MADIT II included 1232 patients in a 3:2 ratio between ICD (742 patients) and drug therapy (490 patients). Average EF was 23% in both groups and 70% of patients were class one or class two. The groups were similar in all respects. During the 20 month follow-up, mortality in the ICD group was 14% versus 20% in the drug group. There is no explanation why new or worsened heart failure was higher in the ICD group. The survival advantage of ICD was no better than drug therapy until 9 months into the study. Also unclear is the impact of not including patients who had bypass surgery in the 3 months before the study started. In the CABG-Patch Trial, such patients got no survival benefit from an ICD after prolonged follow-up. Over half of MADIT II patients had CABG at some time before the study - just not in the previous 3 months. ============================================ ALIVE For 30 years, lidocaine has been the first-line drug for acute ventricular tachycardia/ventricular fibrillation (VT/VF). However, studies suggest that while lidocaine powerfully suppresses PVCs and VT/VF, it may increase risk of death. IV amiodarone also suppresses VT/VF. The ALIVE trial did a direct double-blind comparison of IV lidocaine versus IV amiodarone in similar patients. 347 patients who were revived from cardiac arrest immediately (before hospitalization) got either IV amiodarone (180 patients) or IV lidocaine (167 patients). Drug use was strictly controlled and both groups were very similar in all respects. About 80% of trial patients had VF. 41 (23%) patients survived to hospital admission in the amiodarone group but only 20 (12%) in the lidocaine group. IV amiodarone was better than IV lidocaine for getting out-of- hospital cardiac arrest patients to a hospital alive. Both the ARREST and ALIVE trials show that IV amiodarone is better than lidocaine both out-of-hospital and in emergency rooms and critical care units for VT/VF patients. -------------------------------------------- References: Wyse DG, AFFIRM Investigators. Survival in patients presenting with atrial fibrillation: the atrial fibrillation follow-up investigation of rhythm management (AFFIRM) study. Program and abstracts of the American College of Cardiology 51st Annual Meeting; March 17-20, 2002. Abstract 405-1. Moss AJ, Zareba W, Hall WJ, et al, for the Multicenter Automatic Defibrillator Implantation Trial II Investigators. Prophylactic implantation on a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med. 2002;346:877-883. Dorian P, Cass D, Schwartz , Cooper R, Zelaznikas R, Barr A. Amiodarone as compared with lidocaine for shock-resistant ventricular fibrillation. N Engl J Med. 2002;346:884-890. Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted defibrillator inpatients with coronary artery disease at high risk for ventricular arrhythmia. N Engl J Med. 1996;335:1833-1840. Bigger JT Jr. For the CABG-Patch Investigators. Prophylactic use of implantable cardiac defibrillators in patients at high risk for ventricular arrhythmias after coronary artery bypass graft surgery. N Engl J Med. 1997;337:1569-1575. Ogunyankin K, Singh BN. Mortality reduction by antiadrenergic modulation of arrhythmogenic substrate: significance of combining beta-blockers and amiodarone. Am J Cardiol. 1999;84(9A):76R-82R. Zivin A, Bardy GH. Implantable defibrillators and antiarrhythmic drugs in patients at risk for lethal arrhythmias. Am J Cardiol. 1999;84(9A):63R-68R. MacMahon S, Collins, Peto R, Koster RW, Yusuf S. Effects of prophylactic lidocaine in suspected myocardial infarction: an overview of the results from the randomized, controlled trials. JAMA. 1988;260:1910-1916. Hine LK, Laird N, Hewitt P, Chalmers TC. Meta-analytic evidence against prophylactic use of lidocaine in acute myocardial infarction. Arch Intern Med. 1989;149:2694-2698. Kudenchuk PJ, Cobb LA, Copass MK, et al. Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation. N Engl J Med. 1999;341:871-878. Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: an international consensus on science. Advanced cardiovascular life support. Circulation. 2000;102:(suppl 8):I105-I111. Singh BN. Initial antiarrhythmic drug therapy during resuscitation from sudden cardiac death: a time for a fundamental change in strategy? J Cardiovasc Pharmacol Ther. 2000;5:3-9. Singh BN. Routine prophylactic lidocaine administration in acute myocardial infarction. An idea whose time is all but gone? Circulation. 1992;86:1033-1035.