Primary Prevention of Sudden Cardiac Death in Patients with Heart Failure: How Effective is Current Pharmacologic Therapy?

Abstract

Sudden cardiac death is the most common cause of death in the early stages of heart failure. Implantable cardioverter-defibrillator therapies substantially reduce sudden cardiac death but incur morbidity and are expensive, so are recommended only after failure of optimal medical therapy. Guidelines recommend simultaneous first-line therapy with an angiotensin converting enzyme inhibitor and a beta blocker for heart failure with reduced ejection fraction, with diuretic therapy for symptom relief. The all-cause mortality benefit of angiotensin converting enzyme inhibitors (or angiotensin receptor blockers) in this setting is largely attributable to reduced deaths related to disease progression. Addition of a beta blocker improves both all-cause survival and rates of sudden cardiac death. Where symptoms persist, introduction of a mineralocorticoid receptor antagonist is recommended and can reduce sudden cardiac death. If symptoms continue, substitution of the angiotensin converting enzyme inhibitor with the angiotensin receptor neprilysin inhibitor sacubitril/valsartan significantly reduces all-cause mortality, with the benefit arising from fewer deaths from both sudden cardiac death and worsening heart failure. Further medical interventions should be instituted in specific situations as required. Disappointingly, despite evidence-led guidelines, approximately a quarter of patients who have heart failure with reduced ejection fraction do not receive standard therapy with an angiotensin converting enzyme inhibitor and beta blocker. It remains to be seen if recent guidelines for successive interventions in the event of non-response to standard therapy are more effectively adopted.

Sacubitril/valsartan: An antiarrhythmic drug?

“…Large randomized controlled trials examining ACEi in HF showed no reduction in SCA/SCD. 22 Current guidelines recommend an ICD for primary prevention of SCD in most patients with an ejection fraction (EF) of ≤35. 23 However, optimal medical therapy, including beta blockers, ACEi/ARB, and MRA, promotes LV reverse remodeling and may allow for improvement in left ventricular ejection fraction (LVEF) such that after 9 months of GDMT, up to 67% of such patients with a formerly depressed EF no longer meet EF criteria for a primary prophylactic ICD.…”

“…Perhaps surprisingly, while ACEi and ARB reduce overall mortality and reverse remodeling, they have minimal direct effect on VT/VF/SCD in HF patients. Large randomized controlled trials examining ACEi in HF showed no reduction in SCA/SCD 22 …”