Postgraduate Medicine
ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Antiarrhythmic drugs for ischemic heart disease Jan Koch-Weser To cite this article: Jan Koch-Weser (1976) Antiarrhythmic drugs for ischemic heart disease, Postgraduate Medicine, 59:5, 168-173, DOI: 10.1080/00325481.1976.11714364 To link to this article: http://dx.doi.org/10.1080/00325481.1976.11714364
Published online: 07 Jul 2016.
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Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipgm20 Download by: [Australian Catholic University]
Date: 01 September 2017, At: 11:58
Downloaded by [Australian Catholic University] at 11:58 01 September 2017
antiarrhythmic drugs for ischemie heart disease Jan Koch-Weser, MD
Centre de Recherche Merrell International Strasbourg, France
consider What are the most accurate predictors of ventricular fibrillation? How effective are alprenolol, practolol, propranolol, and quinidine in preventing lethal arrhythmias in ambulatory patients with ischemie heart disease? What factors increase the risk of sudden death following recovery from an acute myocardial infarction?
168
• Severe disturbances of cardiac impulse formation or conduction, leading to inadequate cardiac output, are the most common cause of death in patients with ischemie heart disease (IHD). Electrical interventions are frequently successful in restoring hemodynamically effective cardiac action. Many patients thus saved have adequate cardiac function and survive for many years. Unfortunately, most life-threatening cardiac dysrhythmias occur suddenly and out of immediate reach of the required deviees. Therapy with antiarrhythmic drugs to prevent potentially lethal rhythm disturbances may offer the best immediate hope for reducing mortality from IHD. However, si nee the effectiveness of such drugs remains uncertain and since they can have adverse effects, this therapeutic approach should not become routine before its usefulness has been demonstrated in clinical trials. Definite information on antiarrhythmic drugs in IHD is largely limited to their use in coronary care units (CCUs) in treating patients with rhythm disturbances as a complication of acute myocardial infarction (Ml). Even among these patients many important questions remain unanswered, because controlled studies have been few, the groups studied were small relative to the frequency of mortality due to arrhythmias in this protective setting, and dosage schedules were not individualized. What we know about the best drug therapy for the se patients does not necessarily apply to rhythm disturbances in different settings. The use of antiarrhythmic agents must be considered separately for ambulatory patients with IHD, for patients with acute MI before hospitalization, and for hospitalized patients. Ambulatory Patients
Ventricular fibrillation is the usual cause of sudden death in patients with IHD. About 60% of cases of fatal ventricular fibrillation develop after acute Ml. The risk is such that we cou Id consider chronic prophylactic therapy in ali cases of IHD if a fully effective and safe antiarrhythmic drug were available. Since ali presently marketed drugs are neither, attempts have been made to characterize subgroups of patients who are at highest risk and who would be logical candidates for chronic prophylactic drug therapy.
POSTGRADUATE MEDICINE • May 1976 • Vol. 59 • No. 5
Downloaded by [Australian Catholic University] at 11:58 01 September 2017
High-risk groups- Table l lists proposed criteria for identification ofhigh-risk patients. Two of these are weil substantiated. Survivors of acute MI are cie arly at higher risk of sudden death than IHD patients who have never had an Ml. The incidence of sudden death during the first year after hospital discharge following MI may reach 10%. Ventricular ectopie activity is also associated with increased risk of arrhythmic death. However, we do not yet know which types of ventricular premature contractions (VPCs) are the best index of excess risk and whether ventricular ectopie activity, as detected by electrocardiographie (ECG) monitoring, is more significant if present during usual daily activity than when it appears during imposition of physical exertion or other stress. Chronic therapy with sorne antiarrhythmic agents, including phenytoin, procainamide, propranolol, quinidine, and severa! investigational drugs, can decrease VPCs in sorne patients. Unfortunately, we do not know whether partial suppression of VPCs with drugs benefits IHD patients. The fact that ventricular ectopie activity is an epidemiologie risk factor for death due to arrhythmias does not mean that VPCs are commonly responsible for initiating serious ventricular arrhythmias. They may only be an index of the severity of heart disease. Their suppression with drugs may have no effect on the likelihood of fatal arrhythmias or might even increase it. The fact that a drug is active against VPCs does not guarantee that it has useful antifibrillatory action, and the reverse is also true. The crucial question is whether chronic prophylactic treatment with available antiarrhythmic drugs can protect ambulatory IHD
Vol. 59 •
No. 5 • May 1976 • POSTGRADUATE MEDIC..E
table 1. possible criteria for selectlng ambulatory patients wlth Ischemie heart dlsease for antlarrhythmlc drug therapy Previous myocardial infarction (Ml) Previous ventricular tachycardia or fibrillation Severity of coronary disease (as determined by the presence of angina pectoris and by coronary angiography) lnterval since last Ml Presence of hypertension, cardiomegaly, or congestive heart failure; age; or other patient characteristics possibly associated with increased risk of death from arrhythmias Occurrence of ventricular premature contractions (VPCs), certain VPC patterns, ventricular tachycardia, ventricular fibrillation or conduction disturbances during rest, ambulatory monitoring, exercise testing, or other stress Appearance of prodromes of acute Ml
patients from sudden death. This question must also be posed for subgroups of such patients, including those which show no ventricular ectopie activity. We do not yet have the answers, and we know nothing at ali about the relative merits of various antiarrhythmic drugs. Thus, we cannat be confident that chronic drug therapy will protect a patient with IHD, even if such therapy effectively suppresses ventricular ectopie activity. E.fficacy of drug therapy-Evidence of a protective effect against sudden death of ambulatory patients is strongest for betaadrenergic blocking drugs (eg, alprenolol, practolol). Unfortunately, such evidence does not exist for propranolol, which is the only such drug marketed in the United States. During a two-year period, 114 survivors of acute MI were treated with 400 mg/day of alprenolol and only 3 died suddenly. 1 This mortality rate of 2.6% was significantly (P
ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Antiarrhythmic drugs for ischemic heart disease Jan Koch-Weser To cite this article: Jan Koch-Weser (1976) Antiarrhythmic drugs for ischemic heart disease, Postgraduate Medicine, 59:5, 168-173, DOI: 10.1080/00325481.1976.11714364 To link to this article: http://dx.doi.org/10.1080/00325481.1976.11714364
Published online: 07 Jul 2016.
Submit your article to this journal
View related articles
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipgm20 Download by: [Australian Catholic University]
Date: 01 September 2017, At: 11:58
Downloaded by [Australian Catholic University] at 11:58 01 September 2017
antiarrhythmic drugs for ischemie heart disease Jan Koch-Weser, MD
Centre de Recherche Merrell International Strasbourg, France
consider What are the most accurate predictors of ventricular fibrillation? How effective are alprenolol, practolol, propranolol, and quinidine in preventing lethal arrhythmias in ambulatory patients with ischemie heart disease? What factors increase the risk of sudden death following recovery from an acute myocardial infarction?
168
• Severe disturbances of cardiac impulse formation or conduction, leading to inadequate cardiac output, are the most common cause of death in patients with ischemie heart disease (IHD). Electrical interventions are frequently successful in restoring hemodynamically effective cardiac action. Many patients thus saved have adequate cardiac function and survive for many years. Unfortunately, most life-threatening cardiac dysrhythmias occur suddenly and out of immediate reach of the required deviees. Therapy with antiarrhythmic drugs to prevent potentially lethal rhythm disturbances may offer the best immediate hope for reducing mortality from IHD. However, si nee the effectiveness of such drugs remains uncertain and since they can have adverse effects, this therapeutic approach should not become routine before its usefulness has been demonstrated in clinical trials. Definite information on antiarrhythmic drugs in IHD is largely limited to their use in coronary care units (CCUs) in treating patients with rhythm disturbances as a complication of acute myocardial infarction (Ml). Even among these patients many important questions remain unanswered, because controlled studies have been few, the groups studied were small relative to the frequency of mortality due to arrhythmias in this protective setting, and dosage schedules were not individualized. What we know about the best drug therapy for the se patients does not necessarily apply to rhythm disturbances in different settings. The use of antiarrhythmic agents must be considered separately for ambulatory patients with IHD, for patients with acute MI before hospitalization, and for hospitalized patients. Ambulatory Patients
Ventricular fibrillation is the usual cause of sudden death in patients with IHD. About 60% of cases of fatal ventricular fibrillation develop after acute Ml. The risk is such that we cou Id consider chronic prophylactic therapy in ali cases of IHD if a fully effective and safe antiarrhythmic drug were available. Since ali presently marketed drugs are neither, attempts have been made to characterize subgroups of patients who are at highest risk and who would be logical candidates for chronic prophylactic drug therapy.
POSTGRADUATE MEDICINE • May 1976 • Vol. 59 • No. 5
Downloaded by [Australian Catholic University] at 11:58 01 September 2017
High-risk groups- Table l lists proposed criteria for identification ofhigh-risk patients. Two of these are weil substantiated. Survivors of acute MI are cie arly at higher risk of sudden death than IHD patients who have never had an Ml. The incidence of sudden death during the first year after hospital discharge following MI may reach 10%. Ventricular ectopie activity is also associated with increased risk of arrhythmic death. However, we do not yet know which types of ventricular premature contractions (VPCs) are the best index of excess risk and whether ventricular ectopie activity, as detected by electrocardiographie (ECG) monitoring, is more significant if present during usual daily activity than when it appears during imposition of physical exertion or other stress. Chronic therapy with sorne antiarrhythmic agents, including phenytoin, procainamide, propranolol, quinidine, and severa! investigational drugs, can decrease VPCs in sorne patients. Unfortunately, we do not know whether partial suppression of VPCs with drugs benefits IHD patients. The fact that ventricular ectopie activity is an epidemiologie risk factor for death due to arrhythmias does not mean that VPCs are commonly responsible for initiating serious ventricular arrhythmias. They may only be an index of the severity of heart disease. Their suppression with drugs may have no effect on the likelihood of fatal arrhythmias or might even increase it. The fact that a drug is active against VPCs does not guarantee that it has useful antifibrillatory action, and the reverse is also true. The crucial question is whether chronic prophylactic treatment with available antiarrhythmic drugs can protect ambulatory IHD
Vol. 59 •
No. 5 • May 1976 • POSTGRADUATE MEDIC..E
table 1. possible criteria for selectlng ambulatory patients wlth Ischemie heart dlsease for antlarrhythmlc drug therapy Previous myocardial infarction (Ml) Previous ventricular tachycardia or fibrillation Severity of coronary disease (as determined by the presence of angina pectoris and by coronary angiography) lnterval since last Ml Presence of hypertension, cardiomegaly, or congestive heart failure; age; or other patient characteristics possibly associated with increased risk of death from arrhythmias Occurrence of ventricular premature contractions (VPCs), certain VPC patterns, ventricular tachycardia, ventricular fibrillation or conduction disturbances during rest, ambulatory monitoring, exercise testing, or other stress Appearance of prodromes of acute Ml
patients from sudden death. This question must also be posed for subgroups of such patients, including those which show no ventricular ectopie activity. We do not yet have the answers, and we know nothing at ali about the relative merits of various antiarrhythmic drugs. Thus, we cannat be confident that chronic drug therapy will protect a patient with IHD, even if such therapy effectively suppresses ventricular ectopie activity. E.fficacy of drug therapy-Evidence of a protective effect against sudden death of ambulatory patients is strongest for betaadrenergic blocking drugs (eg, alprenolol, practolol). Unfortunately, such evidence does not exist for propranolol, which is the only such drug marketed in the United States. During a two-year period, 114 survivors of acute MI were treated with 400 mg/day of alprenolol and only 3 died suddenly. 1 This mortality rate of 2.6% was significantly (P
