Delayed and Indirect Effects of Antiarrhythmic Drugs in Reducing Sudden Cardiac Death

Abstract

In the USA, two-thirds of sudden cardiac deaths (SCDs) are caused by sustained ventricular tachycardia and ventricular fibrillation. Implantable cardioverter defibrillator (ICD) therapy has been demonstrated to decrease mortality caused by these arrhythmias, when used both for primary and secondary prevention. However, ICD use is expensive, has proarrhythmic effects and does not prevent ventricular arrhythmias. Antiarrhythmic drugs (AADs) can be used for acute or chronic therapy to prevent ventricular arrhythmias and SCD. Most commonly, AADs are often used in patients with an ICD who have recurrent ICD shocks due to ventricular arrhythmias. Class I AADs are used in patients with a structurally normal heart and are contraindicated in patients with structural heart disease. β-blockers have been demonstrated to be beneficial in preventing mortality and malignant tachyarrhythmias in postmyocardial infarction and congestive heart failure patients, and in patients who have an ICD. Amiodarone has a neutral effect on mortality, while other class III drugs may increase mortality in certain subgroups of patients. Dronedarone, a new class III drug, may reduce mortality, but sufficient data are not available to allow for its use in the prevention of malignant tachyarrhythmias. Few drugs that are not classified as AADs can also prevent arrhythmias, via their beneficial effects on cardiovascular remodeling. These non-ADDs have delayed and indirect effects, which are mediated by the renin-angiotensin-aldosterone system and lipid metabolism - n-3 polyunsaturated fatty acids (fish oil), and statins, and can thus can reduce the likelihood of future malignant ventricular arrhythmias in patients with coronary artery disease or congestive heart failure. The role of chronic drug therapy alone for primary and secondary prevention of SCD is less than desirable because of proarrhythmic and adverse side effects. The non-ADDs are well tolerated and have no proarrhythmic actions, thus their benefit could outweigh risks, although currently there are no concrete data to suggest this.

Effect of Statin Therapy In Ventricular Arrhythmias In Patient With Acute Anterior Myocardial Infarction

“…11 Statin are safe drugs with no proarrhythmic effect and can become a low risk preventive agent for ventricular arrhythmia. 12 The mean age of the patients was 50.7±11.2 years in group I and 51.2±11.5 years in Group II. The age of most of the patients in both groups ranged from 40 to 59 years (65% in group I and 67% in group II), 24 (24%) patients in group I and 23 (23%) patients in group II were of 40 years or younger, 11 (11%) patients in group I and 10 (10%) patients in group II were older than 60 years.…”

Sudden cardiac death and ischemic heart disease

“…В частности, согласно исследова-ниям CAST и CAST-II, назначение препаратов IC-класса пациентам с желудочковыми наруше-ниями ритма и ОИМ в анамнезе сопровождает-ся достоверным увеличением характеристик ВСС [20,21]. Тем не менее существует ряд ситу-аций, при которых назначение ААП может быть оправданным.…”

Medical treatment of sudden cardiac death

“…Было вы-сказано предположение, что сами молекулярные механизмы дислипидемии являются аритмоген-ными, и фармакологическая терапия, направ-ленная на липидные протромботические и про-воспалительные факторы, должна быть одним из основных пунктов фармакологических точек воздействия. В дополнение к ингибиторам ГМГ-КоА-редуктазы к таким препаратам в будущем могут быть отнесены антагонисты лейкотриено-вых рецепторов, ингибиторы изофермента цик-лооксигеназы, антагонисты фактора агрегации тромбоцитов и антагонисты цитокинов [31].…”