Propranolol-withdrawal rebound phenomenon. Exacerbation of coronary events after abrupt cessation of antianginal therapy

The New England Journal of Medicine
R R MillerD T Mason


Effects on anginal symptoms of sudden withdrawal of large doses of propranolol or placebo were evaluated in 20 patients in a double-blind crossover efficacy trial requiring sudden cessation of the agent. With propranolol, 160 to 320 mg per day for six and 12 weeks, no patients had increased angina or nitroglycerin use, and there were no hospitalizations or deaths. However, within two weeks of discontinuance of propranolol, untoward ischemic events developed in 10 patients. Six had serious withdrawal complications: intermediate coronary syndrome in three, and ventricular tachycardia, fatal myocardial infarction, and sudden death in one each. In four patients discontinuance of placebo increased anginal symptoms; in the remaining 10, ischemic symptoms were not provoked. The rebound phenomenon was related to degree of pre-propranolol angina and relief of pain by the agent. Thus, chronically administered propranolol should be gradually reduced, and activity restricted during its withdrawal.


Mar 1, 1975·Annals of Internal Medicine·R Allen, B Genovese
May 12, 1973·Lancet·R G DiazB Levitt
Nov 1, 1974·Annals of Internal Medicine·E L AldermanD C Harrison
Apr 1, 1973·Minerva cardioangiologica·B MagnaniM Sanguinetti
May 1, 1974·Circulation·M A LichtmanA A Whitbeck
Mar 1, 1969·Progress in Cardiovascular Diseases·R A Bruce, T R Hornsten


Aug 1, 1979·Journal of Clinical Pharmacology·S B GarbusF A Hubbell
Apr 15, 1980·Documenta Ophthalmologica. Advances in Ophthalmology·F E Ros, C L Dake
Jan 1, 1985·European Journal of Clinical Pharmacology·A D Struthers, C T Dollery
Jan 1, 1984·European Journal of Clinical Pharmacology·K S Kiyingi, J Shaw
Jan 1, 1976·European Journal of Clinical Pharmacology·O L Pedersen
Jan 1, 1983·European Journal of Clinical Pharmacology·B SilkeS H Taylor
Aug 1, 1982·American Heart Journal·R J WaldenB N Prichard
Aug 19, 1983·European Journal of Pharmacology·T E Tenner
Mar 1, 1978·Life Sciences·G KunosL Mucci
Jan 1, 1983·Pharmacology & Therapeutics·A J Scriven, P J Lewis
Jan 1, 1983·Pharmacology & Therapeutics·M J Kendall, L Beeley
Jan 1, 1982·General Pharmacology·R H Kennedy, T E Donnelly
Oct 1, 2013·Journal of Hepatology·Phillip S Ge, Bruce A Runyon
Feb 5, 2008·Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology·Alan W AhlbergGary V Heller
Aug 4, 1998·International Journal of Cardiology· Martsevich SYuV I Metelitsa
Jan 1, 1983·Journal of the American College of Cardiology·A M Watanabe
Mar 21, 1998·Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology·P J HuangC T Su
Apr 22, 1976·The New England Journal of Medicine·O B Holland, N M Kaplan
Nov 29, 1979·The New England Journal of Medicine·J G Gerber, A S Nies
Apr 2, 1981·The New England Journal of Medicine·Norwegian Multicenter Study Group
Aug 26, 1982·The New England Journal of Medicine·D LebrecJ P Benhamou
Aug 8, 2009·The Journal of Biological Chemistry·Lin XuDonald R Menick
Sep 23, 2008·American Journal of Therapeutics·Jeffrey S Borer, Jean-Yves Le Heuzey
Jun 1, 1978·British Journal of Clinical Pharmacology·F WaagsteinA Hjalmarson
Oct 1, 1979·Acta Anaesthesiologica Scandinavica·H Tydén, C J Westerholm
May 1, 1980·Clinical and Experimental Pharmacology & Physiology·J D EnglandM Carlton
Sep 1, 2006·International Journal of Clinical Practice·L F CorfieldD Wilson
Oct 8, 2005·BMJ : British Medical Journal·Donald RedelmeierAlexander Kopp
Jan 1, 1983·British Heart Journal·B HockingsM M Webb-Peploe
Jun 1, 1984·British Heart Journal·O J OrmerodM C Petch
Feb 1, 1977·Postgraduate Medical Journal·B FagherS E Svensson
May 1, 1980·The Journal of Clinical Investigation·R D AaronsP B Molinoff
Jun 1, 1997·Anesthesia and Analgesia·M D SeebergerN B Schiller
Sep 17, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Gwenaëlle L ClarkePeter G Smith
Oct 5, 1984·The American Journal of Medicine·D T LowenthalK Conry
Apr 29, 1977·Virchows Archiv. A, Pathological Anatomy and Histology·O PenttiläP Siltanen
Feb 25, 1978·British Medical Journal
Sep 1, 1987·Medical Toxicology and Adverse Drug Experience·C F George, D Robertson
Mar 16, 2012·Journal of Cardiothoracic and Vascular Anesthesia·Robert B SchonbergerMatthew M Burg
Oct 1, 1980·The American Journal of Cardiology·F G Estafanous, R C Tarazi
Jul 1, 1979·American Heart Journal·F LeuteneggerD Burckhardt
Sep 8, 1979·Lancet·C Prys-Roberts
May 1, 1987·Progress in Cardiovascular Diseases·N A Silverman, S Levitsky
Nov 1, 1976·Progress in Cardiovascular Diseases·M E ConollyC T Dollery
Jul 1, 1987·International Journal of Cardiology·A Simon, J Levenson
Aug 1, 1982·American Heart Journal·W H Aellig
Mar 1, 1979·American Heart Journal·M G MyersG Wisenberg
Jan 1, 1982·British Journal of Clinical Pharmacology·E SzécsiE Lang
Jan 1, 1980·British Journal of Pharmacology·S P Baker, L T Potter
Feb 1, 1982·Journal of Clinical Pharmacology·J B ChambersA K Suda
Jan 1, 1982·British Journal of Clinical Pharmacology·W J Louis, J J McNeil
Feb 1, 1978·The Annals of Thoracic Surgery·M M KirshH Sloan
Apr 1, 1978·The Annals of Thoracic Surgery·A PetersonM M Kirsh
Oct 23, 1985·The American Journal of Cardiology·J G Reves, P Flezzani
Dec 22, 1999·The Journal of the American Dental Association·C ZhangJ T Hamilton
Oct 20, 1999·Journal of Molecular and Cellular Cardiology·P E MorganH E Cingolani
Dec 1, 1981·The American Journal of Cardiology·D S Goldstein
Apr 1, 1978·The American Journal of Cardiology·R A ShiroffA H Hayes
Jan 1, 1988·The Journal of Allergy and Clinical Immunology·J H Toogood
Dec 8, 2004·Annales Françaises D'anesthèsie Et De Rèanimation·N DantonV Piriou
Jul 28, 2016·The Journal of Pharmacology and Experimental Therapeutics·Shahrooz Nasrollahi-ShiraziChristian Nanoff
May 19, 2009·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·M J C CarmonaS R C J Santos
May 27, 2005·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·M J C CarmonaS R C J Santos
Nov 1, 1986·International Journal of Cardiology·R J VechtW B Cooper
May 1, 1987·International Journal of Cardiology·R J Northcote
Jun 26, 2017·Psychotherapy and Psychosomatics·Guy ChouinardMasaomi Iyo
Nov 15, 2017·International Journal of Molecular Sciences·H M Mazhar AsjadChristian Nanoff
Aug 1, 1978·Circulation·D G Shand, A J Wood
Jul 1, 1980·Hypertension·D W JohnsS C Williams
Jun 1, 1979·Circulation·S NattelG Van Loon
Jan 1, 1986·British Heart Journal·P R Walker
Sep 1, 1982·Journal of Clinical and Hospital Pharmacy·P L Weissberg
Jun 1, 1983·Journal of Clinical and Hospital Pharmacy·P Foëx
Jan 1, 1982·Acta Anaesthesiologica Scandinavica. Supplementum·S ReizM Ostman
Jan 15, 2011·Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions·William J KostisIgor F Palacios
Sep 13, 2011·Congestive Heart Failure·Marco A Caccamo, Peter M Eckman
Sep 13, 2019·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Xiying YangLiping Zou
Mar 1, 1992·Postgraduate Medicine·J N Dalal, A C Jain
Jan 1, 1982·Acta Anaesthesiologica Scandinavica. Supplementum·J PonténA Hjalmarson
Jan 1, 1982·Acta Anaesthesiologica Scandinavica. Supplementum·J PonténD Lundberg
Sep 1, 1986·Medical Toxicology·R V Lewis, D G McDevitt
Jan 1, 1982·Acta Medica Scandinavica. Supplementum·P Hjemdahl, G Olsson
Jun 1, 1989·Journal of Pharmacokinetics and Biopharmaceutics·J J LimaH Boudoulas
Feb 1, 1980·Postgraduate Medicine·L E Feinberg
Aug 1, 1980·Postgraduate Medicine·F A Hubbell, M A Weber
Aug 1, 1981·British Journal of Clinical Pharmacology·J WebsterJ C Petrie
Sep 18, 2007·Journal of Perioperative Practice·Manish Chand, Natalie Dabbas
Jan 1, 1982·British Journal of Clinical Pharmacology·R E Rangno, S Langlois
Nov 1, 1976·Postgraduate Medicine·W S Aronow
Apr 12, 2000·British Journal of Clinical Pharmacology·J M KennedyI G Tucker
Jan 1, 1982·Acta Anaesthesiologica Scandinavica. Supplementum·P FoëxG R Cutfield
Jan 1, 1982·British Journal of Clinical Pharmacology·B N Prichard, R J Walden
Apr 22, 2020·Proceedings·Madison K Bangert, Gabriel M Aisenberg
Aug 1, 1988·Postgraduate Medicine·D Thompson, L Ampel
Mar 1, 1976·The Journal of Dermatologic Surgery·H Drasin, I Sharkey
Aug 1, 1979·The International Journal of the Addictions·D Arensberg, N K Wenger
Jun 1, 2001·Canadian Journal of Anaesthesia = Journal Canadien D'anesthésie·Joel Parlow
Feb 23, 2020·Current Heart Failure Reports·Patrick Tran, Prithwish Banerjee
Aug 1, 1981·British Journal of Clinical Pharmacology·J F De PlaenC Van Ypersele de Strihou
May 9, 2020·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Goran KoracevicZaklina Ristic
Jul 3, 2020·Frontiers in Medicine·Ekamol TantisattamoAlpesh Amin

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