Antiarrhythmic Drugs A practical guide – Part 8 ppsx

For instance, given the almost universal risk of proarrhythmia, one should often consider placing patients on a cardiac monitor while antiarrhythmic drugs are being initiated be-cause, a

128 Chapter 9

Table 9.3Effect of antiarrhythmic drugs on pacing thresholds

Increase at normal drug levels Increase at toxic drug levels No increase

Amiodarone Disopyramide

Sotalol

several ways and is often clinically significant Two major problems caused by antiarrhythmic drugs are that they can change the en-ergy required for successful defibrillation and they can change the characteristics of the arrhythmia being treated

The effect of antiarrhythmic drugs on defibrillation energy re-quirements is an important consideration because increasing the defibrillation threshold can render an ICD ineffective The effects of various drugs on defibrillation energy requirements are summarized

in Table 9.4 In general, drugs that block the sodium channel increase defibrillation energy requirements (thus, Class IC drugs have the most profound effect, and Class IA and Class IB drugs tend to have proportionally lesser effects), and drugs that block the potassium channels (e.g., sotalol) decrease defibrillation energy requirements Drugs that affect both the sodium and potassium channels (i.e., Class

IA drugs and amiodarone) have mixed effects—sometimes they in-crease and sometimes they dein-crease defibrillation energy require-ments If one must prescribe a drug that has the potential of increas-ing defibrillation energy requirements for a patient who has an ICD, one should consider retesting defibrillation thresholds after the drug has been loaded to be sure that the ICD is still capable of delivering sufficient energy to reliably defibrillate the patient

Antiarrhythmic drugs can also interact with ICDs by changing the characteristics of a patient’s ventricular tachycardia By slowing the

Table 9.4Effect of antiarrhythmic drugs on defibrillation thresholds

Propafenone Procainamide

Mexiletine

Common adverse events with antiarrhythmic drugs 129

rate of ventricular tachycardia, a drug can render the arrhythmia more amenable to antitachycardia pacing, which potentially makes the ICD more effective On the other hand, by slowing the rate of ventricular tachycardia below the recognition rate of the ICD, a drug can cause the ICD to fail to recognize (and therefore fail to treat) re-current arrhythmias Antiarrhythmic drugs can also cause reentrant ventricular arrhythmias to recur more frequently or even to become incessant, thus inducing frequent ICD therapy, which, in turn, can cause excessive discomfort and premature battery depletion of the ICD In general, when one is compelled to add an antiarrhythmic drug to the treatment regimen of a patient with an ICD, one should consider electrophysiologic testing to reexamine the characteristics

of the patient’s arrhythmias and to be sure that the ICD is optimally programmed to treat the arrhythmias

Reference

1 Echt DS, Liebson PR, Mitchell B, et al Mortality and morbidity in patients receiving encainide, flecainide or placebo N Engl J Med 1991;324:781

Part 3

Antiarrhythmic drugs in the treatment of cardiac arrhythmias

C H A P T E R 1 0

Basic principles of using

antiarrhythmic drugs

The first two sections of the book concerned the mechanisms of car-diac arrhythmias, the mechanism of action of antiarrhythmic drugs, and the features of specific antiarrhythmic drugs In this final sec-tion, that information is applied to the use of antiarrhythmic drugs

in the treatment of specific cardiac arrhythmias Chapter 10 reviews some basic principles that should be kept in mind when using an-tiarrhythmic drugs

On the basis of the generally limited efficacy of antiarrhythmic drugs as well as their inherent propensity to cause serious problems, the first principle should be completely self-evident; namely, one should avoid using antiarrhythmic drugs whenever possible Thus, when one has decided to prescribe an antiarrhythmic drug, the final step before actually writing the order should be to ask, “Does this patient really need this drug?” There are only two general conditions

in which using an antiarrhythmic drug is entirely appropriate: first, when an arrhythmia needs to be suppressed because it threatens to cause death or permanent harm, and second, when an arrhythmia needs to be suppressed because it produces significant symptoms Before prescribing an antiarrhythmic drug, the physician should be certain that the arrhythmia meets one of these two conditions The second basic principle is to keep the goal of treatment clearly

in mind and to tailor the aggressiveness of one’s therapy accordingly

If one is treating an arrhythmia to prevent death or permanent in-jury, for instance, a relatively aggressive approach may be appropri-ate and necessary In theory, if the object is to spare life and limb, one should err on the side of efficacy, perhaps willingly accepting the risk of certain drug toxicities In practice, however, as we will see in Chapters 11 and 12, there are relatively few instances today where one ought to rely primarily on antiarrhythmic drugs to treat arrhythmias that threaten life and limb

133

134 Chapter 10

On the other hand, if one is treating an arrhythmia to relieve symptoms, a more circumspect approach is appropriate In these cases, one generally should use a stepwise strategy, beginning with milder, less risky forms of treatment, and carefully reassessing the risk-to-benefit ratio before each potential escalation of therapy All too often physicians pursue the treatment of relatively insignificant arrhythmias with Ninja-like intensity, an error that can result in unnecessary injury or death

The final basic principle of using antiarrhythmic drugs is that, if one feels compelled to expose a patient to the risk of the drugs, one should also feel compelled to take every reasonable precaution

to reduce the risks For instance, given the almost universal risk

of proarrhythmia, one should often consider placing patients on a cardiac monitor while antiarrhythmic drugs are being initiated be-cause, although proarrhythmia can occur any time during the course

of treatment, a significant proportion of these events occur during the first 3 or 4 days of drug usage Most importantly, one must take great care in deciding which drug to use The choice must be indi-vidualized

The accompanying tables summarize the factors that should be considered in choosing antiarrhythmic drugs for patients with and without significant underlying cardiac disease

Some drugs are plainly contraindicated for particular patients Pro-cainamide, for instance, should not be used in patients with systemic lupus erythematosus; quinidine should not be used in patients with chronic colitis; patients with severe lung disease (in whom mild drug-induced pulmonary toxicity goes a long way) ideally should not receive amiodarone; patients with a history of heart failure should not receive drugs with negative inotropic effects

Beyond these obvious individual considerations, the presence or absence of underlying heart disease is the most important variable in choosing an antiarrhythmic drug, because heart disease predisposes patients to reentrant circuits and, therefore, to proarrhythmia As shown in Table 10.1, beta blockers and Class IB drugs are the safest choice regardless of whether the patient has underlying heart dis-ease Class IC drugs are reasonably safe for patients with normal hearts, but because they very frequently exacerbate reentrant ven-tricular tachyarrhythmias, they are to be avoided in patients with underlying cardiac disease Class IA drugs carry a moderate risk of toxicity for patients without cardiac disease because they cause both torsades de pointes and end-organ toxicity; in patients with cardiac

Basic principles of using antiarrhythmic drugs 135

Table 10.1Relative overall risk of serious toxicity from antiarrhythmic drugs∗

Increasing order of risk for patients Increasing order of risk for patients with no underlying heart disease with underlying heart disease†

Class IC Sotalol and dofetilide

Sotalol and dofetilide Amiodarone

Amiodarone‡ Class IC (should not use)

∗Ranking of relative risks takes into account the risk of both proarrhythmia and

end-organ toxicity.

†For patients with underlying heart disease, the ranking changes because these

patients have a much higher propensity for proarrhythmia Amiodarone rises in rank because of its relatively low risk of producing proarrhythmia Class IC drugs should virtually never be used in these patients.

‡For patients without underlying heart disease, its impressive range of end-organ

toxicity makes amiodarone the riskiest drug.

disease, they also add a moderate risk of exacerbation of reentrant arrhythmias Sotalol and dofetilide carry a moderate risk of torsades

de pointes for all patients Amiodarone carries a substantial risk of significant end-organ toxicity for all patients, though only a rela-tively small risk of proarrhythmia

Table 10.2 ranks the efficacy of antiarrhythmic drugs for atrial and ventricular tachyarrhythmias and for atrioventricular (AV)-node-dependent arrhythmias For atrial tachyarrhythmias, Class IA drugs, sotalol, and dofetilide, are roughly equal in efficacy Class

IC drugs and amiodarone are somewhat more effective than are Class IA drugs, and Class IB drugs have virtually no efficacy for these arrhythmias Most antiarrhythmic agents have some degree

of efficacy against AV-node-dependent arrhythmias For ventricu-lar tachyarrhythmias, Class II and Class IB drugs are least effective; amiodarone is most effective

Table 10.3 synthesizes the data from Tables 10.1 and 10.2 to gen-eralize about the potential drugs of choice for atrial and ventricular tachyarrhythmias (keeping in mind that drug selection must be in-dividualized in every case) The main consideration is always to bal-ance efficacy with safety

136 Chapter 10

Table 10.2Increasing order of relative efficacy for tachyarrhythmias

tachyarrhythmias∗ tachyarrhythmias† tachyarrhythmias

Amiodarone

Verapamil§

Adenosine

∗Atrial tachycardia, atrial fibrillation, and atrial flutter.

†AV-nodal reentry and macroreentry (bypass-tract-mediated).

‡When used orally for maintenance of sinus rhythm.

§When used intravenously for acute termination of the arrhythmia.

The drug of choice in treating both atrial and ventricular tach-yarrhythmias depends on the presence or absence of underlying cardiac disease For instance, in the absence of heart disease, Class IC drugs may offer the most favorable balance of efficacy and safety in the treatment of atrial tachyarrhythmias However, in the presence

of underlying heart disease, Class IC agents (because of their im-pressive propensity to exacerbate reentrant ventricular arrhythmias)

Table 10.3Drugs of choice for atrial and ventricular arrhythmias∗

Underlying heart disease absent Underlying heart disease present

arrhythmias† arrhythmias‡ arrhythmias arrhythmias

Class IC

Sotalol

Class IA

Class II Class IB Sotalol Class IC Class IA Amiodarone

Sotalol Amiodarone Class IA

Amiodarone Sotalol Class IA

∗Drugs are listed in decreasing order of choice.

†Atrial tachycardia, atrial fibrillation, and atrial flutter.

‡Complex ventricular ectopy, ventricular tachycardia, and ventricular fibrillation.

Basic principles of using antiarrhythmic drugs 137

should never be used For ventricular arrhythmias, the primary con-sideration in patients without underlying heart disease (i.e., patients

in whom the risk for sudden death is usually very low) is to be sure not to increase the risk of death by exposing the patients to the risk

of proarrhythmia Thus, in choosing drug therapy, one should err on the side of safety; Class II and Class IB drugs should be considered despite their limited effectiveness As soon as one moves beyond these two classes of drugs, one begins accepting a substantial risk of proarrhythmia or other significant toxicity On the other hand, for patients with underlying heart disease who require therapy for ven-tricular arrhythmias, efficacy (which here includes avoiding proar-rhythmia) is often the primary consideration Thus, amiodarone

is often the first drug considered despite its potential for causing long-term end-organ toxicity In the last column of Table 10.3, for drugs listed as secondary choices after amiodarone, not only do the odds of efficacy decrease but the risk of proarrhythmia increases

To summarize, when it comes to using antiarrhythmic drugs, there are no pretty choices The best choice is to avoid them altogether

If this is not possible, one must proceed with the goals of treatment clearly in mind and take every precaution to avoid producing more problems than are caused by the arrhythmias being treated

C H A P T E R 1 1

Treatment of

supraventricular

tachyarrhythmias

Traditionally, clinicians have tended to divide the supraventricu-lar tachyarrhythmias into two broad categories: paroxysmal atrial tachycardia (PAT) and atrial flutter and atrial fibrillation The term PAT has fallen into disfavor of late (it is an artifact of the days before the mechanisms of supraventricular arrhythmias were understood), but this bimodal categorization of supraventricular arrhythmias still lends itself nicely to a discussion of therapy

Paroxysmal atrial tachycardia

PAT is a term used to describe regular supraventricular tachyarrhyth-mias that occur with sudden onset and terminate equally suddenly Thus, PAT is a catchall phrase that incorporates virtually all reen-trant supraventricular arrhythmias except atrial fibrillation and atrial flutter More than 50% of PATs are caused by atrioventricular (AV) nodal reentrant tachycardia, and approximately 40% are caused by macroreentrant tachycardia mediated by an overt or concealed by-pass tract The remaining 10% or so of PATs are caused by reentrant atrial tachycardia or sinoatrial (SA) nodal reentrant tachycardia (see Chapter 1 for a description of the mechanisms of supraventricular arrhythmias)

The acute and chronic therapies of PAT are listed in Table 11.1 Acute therapy is aimed at terminating an episode of PAT In gen-eral, this is easy to achieve Since the AV node or the SA node is an integral part of the reentrant circuit in 90–95% of PATs (the excep-tion is reentrant atrial tachycardia, an arrhythmia that can usually

be recognized by the presence of an unusual P-wave axis), maneu-vers or drugs that produce transient SA nodal or AV nodal block are

138

Treatment of supraventricular tachyarrhythmias 139

Table 11.1Acute and chronic treatment of PAT

Acute treatment

Goal: Termination of the arrhythmia

Step 1: Vagal maneuvers, such as Valsalva (may be tried by the patient before seeking medical attention)

Step 2: Intravenous administration of adenosine or verapamil

Termination by antitachycardia pacing or DC cardioversion (rarely necessary) Chronic treatment

Goal: Prevention of recurrences

Infrequent or easy-to-terminate recurrences—no specific chronic therapy may

be necessary

Other types of recurrences

Treatment of choice—EP testing with RF ablation to abolish reentry Drug therapy—one or more of several drugs may be tried empirically (see Table 10.2)

EP, electrophysiologic; RF, radiofrequency.

highly effective in terminating supraventricular arrhythmias Many patients who have recurrent PAT can therefore terminate episodes themselves by performing maneuvers that cause a sudden increase

in vagal tone Such maneuvers include Valsalva, carotid massage, ocular massage, and dunking one’s face in ice water If pharmaco-logic intervention is necessary, the treatment of choice is intravenous adenosine, which is virtually always effective—in fact, if adenosine fails to terminate the arrhythmia, the diagnosis of PAT needs to be seriously reconsidered Intravenous verapamil is also highly effec-tive Other AV nodal blocking drugs (digoxin and beta blockers) are effective but have a much longer onset of action and, once loaded, their effect persists Unless these drugs are being administered for chronic use, they are almost never given for acute treatment of PAT Antitachycardia pacing techniques are also highly effective in termi-nating supraventricular arrhythmias, but since so many less invasive options are available, pacing is rarely used unless an atrial pacemaker

is already in place

The chronic therapy for PAT has undergone a revolution in recent decades Prior to the 1990s, pharmacologic therapy was the only viable option for most patients Although the choices of drug therapy for the chronic treatment of PAT are broad and include all AV nodal blocking agents (beta blockers, calcium blockers, and digoxin) and Class IA, Class IC, and Class III antiarrhythmic drugs, in earlier days