• DOI:10.1056/nejm199207233270403
• Corpus ID: 9094806

Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction.

@article{Rogers1992EffectOT,
  title={Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction.},
  author={W J Rogers and Ae Epstein and J G Arciniegas and G Crossley and Sm Dailey and G. Neal Kay and R E Little and W A Maclean and S E Papapietro and Vj Plumb and S. Silber and A Baker and K Carlisle and N Cohen and M Cox and C. Thomas and L Levson and D Vonhagel and A. E. Walton and C M Pratt and John J. Mahmarian and G Morris and Rj Capone and E I Berger and C A Chmielewski and Larry Gorkin and Ahmad Khan and Kenneth S. Korr and K Handshaw and Eugene Connolly and Drew Fitzpatrick and T Cameron and D. George Wyse and Hj Duff and L. Brent Mitchell and Am Gillis and J. Wayne Warnica and Rs Sheldon and Nr Lesoway and Joyce C. Kellen and C Hale and Melanie E. Inkster and Michael A. Brodsky and L J Wolff and Byron J. Allen and Robin Zelman and George Thomas and Guillermina Caudillo and D. Takeda and C. Sherwood and R. Ranazzi and Elliot Rapaport and Ml Dohrmann and Stephen Raskin and Dw Drew and Carolyn Somelofski and J W Danforth and Py Hui and P Johnson and Labarca and Albert L. Waldo and Carlson and Ds Adler and Jb Holland and Cm Buchter and Rc Bahler and F X Pamelia and R A Josephson and Rw Henthorn and J T Zuelgaray and Kathryn Wood and Patrick Redmon and Manuel Vargas and Laura Vargo and Sebastian Schaller and C Kobus and Nl Choban and J. Thomas Bigger and H Greenberg and Jj Gregory and Js. Hochman and Glauco Radoslovich and Js Steinberg and Stephen T. Rothbart and Robert Joseph Case and E Dwyer and A Squatrito and Michael T. Kelly and J Campion and Deborah Tormey and Robert Anthony and Edward Callaghan and Max Laitman Chapnick and Brian John Ripley and C{\'a}ssio Aparecido Pereira Fontana and R C Schlant and Daniel Arensberg and Jacopo Dal Corso and Jw Hurst and Dc Morris and S W Sherman and B Silverman and Melissa A. Silverman and Js Roberts and S. B. Ballou and Vd Jeffries and Barbara E. Brackney and A. Allen Seals and John Hartley and R G Baker and Kerry Gilmour and Sb Baker and Joseph B Howard and R Y Katz and G A Besch and David C. Brill and Robert Dibianco and Daniel Donohue and Georgette Fisher and C Fredi Francis and D M Friedman and David Goldberg and Samuel D Goldberg and G. Koss and L J Larca and Roger Leonard and Keith M. Lindgren and James A. Ronan and Andrew Rosenblatt and David Rosing and Allison C. Ross and A Rotsztain and Fayaz A. Shawl and T Sinderson and Ronald Stevenson and Barbara Ann Tinker and Jacob Varghese and J M Yackee and Heather Bigham and W Franklin and Robert L. Gold and George Graham and Daniel Grossberg and Rose Marie Hoare and W Levy and Tariq Mahmood and Elizabeth Tannenbaum and W Tullner and E Eisenhower and Therese S. Geraci and Lars Wilhelmsen and Robert H Bergstrand and B O Fredlund and Axel F. Sigurdsson and Ramon Sivertsson and Karl Swedberg and Birgitta Houltz and Ingela K Wiklund and Gunn Schlyter and Gunnel Hedelin and M Leijon and J. Morganroth and Julie Carver and Leonard N. Horowitz and Steven P. Kutalek and Louis A. Papa and Jon Sandberg and Maiskov Victor and S Cesare and Cynthia S. Vrabel and Kathryn M. Talarico and Scott J Luhmann and David P. Palazzo and Sidney O. Goldstein and A. David Goldberg and Howard I Frumin and Douglas C. Westveer and M Debutlier and John R. Schairer and Robert J. Stomel and D Frank and Regina Jarandilla and Debra L Davey and Cathrine Hasse and S Shinney and Jh Morledge and D J Farnham and Ph Hinderacker and W. Daniel Musser and K Devries and James M. Kushner and R. Govinda Rao and Dt Peterson and Cs Mccauley and Ts Bergen and Ko Bowman and Amelie r. Gillman and Lauara Fuller and James L. Obrien and Jh Morledge and A Demaria and Cs Kuo and Jm Kammerling and J Corum and Mads Thiemann and Raymond Paul Schrodt and Robert W. Peters and Fr{\'e}d{\'e}ric Laurent Sutton and Stephen S. Gottlieb and G C Papuchis and Thomas A. Mattioni and L Todd and Celeste Cusack and Justin Scheck and Sks Huang and J A Alpert and J M Gore and Mona M. Ryan and P Collettwilley and Ramez Chahine and Rf Sequeira and M L Lowery and Lm Delgado and Jl Correa and L. Sayagu{\'e}s Laso and Morrison Hodges and David M. Salerno and B Anderson and Rory Collins and Pablo Denes and D N Dunbar and Gregory Granrud and J. Mark Haugland and W T Hession and John McBride and Cc Gornick and Js Simonson and M Tolins and A Ettinger and S Peterson and R Slivken and L. Grimaldi and Denis Roy and Pierre Th{\'e}roux and Robert Lemery and D Morissette and Denise Beaudoin and Laurence Girard and {\'E}ric Lavall{\'e}e and Jh Mcanulty and S Reinhart and G. Pattengill Maurice and Esther Murphy and Jack Kron and Christy Marchant and J. Boxer and Lonnie Princehouse and K Sinner and Donald S. Beanlands and Ross A. Davies and Martin S. Green and W Williams and Mj Baird and Linda Garrard and Sucel Tamayo Heal and A Haspect and John Bishop Borthwick and Lisa Marois and Kirsten Woodend and Toshio Akiyama and Wb Hood and R M Easley and G. Ryan and G Kenien and Mary Johnson Patt and David J. Kazierad and A M Goldfarb and Llewyn Butler and Ml Keller and Paige Stanley and James M. Peebles and D Syrocki and Diego Cacho Lavin and James A. Schoenberger and Pr Liebson and Nj Stamato and At Petropulos and Tanya M. A. Buckingham and Tracy Remijas and Joanne Kocourek and K. Janko and Ah Barker and Jl Anderson and Re Fowles and Tb Keith and Cb Williams and Fl Moreno and Enver Can Doran and B Fowler and Kaye L. Summers and C White and Genta Ohara and J L Rouleau and Sylvain Plante and Charles Vincent and D Bouchard and R G Zoble and J{\'e}sica Abad{\'i}a Otero and W B Bugni and Km Schwartz and Ur Shettigar and J Brewington and J Umberger and Jd Zachary B. Cohen and Preben Bjerregaard and W. Donald Hamilton and Madeleine Garner and S Anderson and Nadia Abdalhafid Elsherif and Sn Ursell and George E. Gabor and B Ibrahim and Mohammed Hani Assadi and M L Brezsnyak and Avital Porter and A Staniorski and Rl Woosley and D. M. Roden and W B Campbell and Ds Echt and Jt Lee and Kt Murray and J. Christopher Spell and St Bonhotal and L Piper Jared and Tig Thomas and F Goldner and D W Richardson and D W Romhilt and Ka Ellenbogen and Bb Bane and Joanna Fields and Steven W. Shrader and E Powell and Cf Chaffin and A Wells and K. Conway and Ev Platia and Susan Odonoghue and Cm Tracy and Nada Mohammed Ahmed Ali and Patrick J. Bowen and Km Brooks and William J. Oetgen and Lt Weston and Peter E. Carson and D Obiasmanno and Jane Harrison and Amy R. Saylor and Sarah Powell and Cm. Haakenson and Sather and La Malone and A P Hallstrom and Ruth Mcbride and H. Greene and Mm Brooks and Robert B Ledingham and Ra Reynoldshaertle and Melissa Huther and M Scholz and Monica Rodriguez Morris and L M Friedman and Eleanor B. Schron and Joel I Verter and Cheryl Jennings and Michael A. Proschan and J. D. Bristow and Dl Demets and Caroline Fisch and A S Nies and Jeremy N. Ruskin and Hans D. Strauss and L Walters},
  journal={The New England journal of medicine},
  year={1992},
  volume={327 4},
  pages={
          227-33
        }
}

• W. Rogers, A. Epstein, +381 authors L. Walters
• Published 1992
• Medicine
• The New England journal of medicine

BACKGROUND
The Cardiac Arrhythmia Suppression Trial (CAST) tested the hypothesis that the suppression of asymptomatic or mildly symptomatic ventricular premature depolarizations in survivors of myocardial infarction would decrease the number of deaths from ventricular arrhythmias and improve overall survival. The second CAST study (CAST-II) tested this hypothesis with a comparison of moricizine and placebo.

METHODS
CAST-II was divided into two blinded, randomized phases: an early, 14-day exposure phase that evaluated the risk of starting treatment with moricizine after myocardial infarction (1325 patients), and a long-term phase that evaluated the effect of moricizine on survival after myocardial infarction in patients whose ventricular premature depolarizations were either adequately suppressed by moricizine (1155 patients) or only partially suppressed (219 patients).

RESULTS
CAST-II was stopped early because the first 14-day period of treatment with moricizine after a myocardial infarction was associated with excess mortality (17 of 665 patients died or had cardiac arrests), as compared with no treatment or placebo (3 of 660 patients died or had cardiac arrests); and estimates of conditional power indicated that it was highly unlikely (less than 8 percent chance) that a survival benefit from moricizine could be observed if the trial were completed. At the completion of the long-term phase, there were 49 deaths or cardiac arrests due to arrhythmias in patients assigned to moricizine, and 42 in patients assigned to placebo (adjusted P = 0.40).

CONCLUSIONS
As with the antiarrhythmic agents used in CAST-I (flecainide and encainide), the use of moricizine in CAST-II to suppress asymptomatic or mildly symptomatic ventricular premature depolarizations to try to reduce mortality after myocardial infarction is not only ineffective but also harmful.