Prevention of coronary plaque rupture or a direct cardioprotective effect reducing VA has been suggested. Experimental ischemia/reperfu- sion models demonstrate a cardioprotective effect of statins, and a large observational analysis observed this effect in humans.S5.1.5.2-42,S5.1.5.2-56 S5.1.5.2-58 This was ex- plored further in HF in several secondary analyses of patients on statins in ICD prevention trials, including the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy), SCD-HeFT, AVID (Antiarrhythmics versus Implantable and DEFINITE (DEFibrillators In Non-Ischemic Cardiomyopathy Treatment Evaluation) trials that showed less SCD risk among the patients However, this general effect in HF was not confirmed in 2 prospective RCTs of rosuvastatin in HF; the CORONA (Controlled Rosu- vastatin Multinational Trial in Heart Failure) and GISSI- HF (Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca-Heart Failure).S5.1.5.2-63,S5.1.5.2-64 It appears that the beneficial effects of statins are con- CLINICAL STATEMENTS AND GUIDELINES fined to the population with or at risk for atheroscle- rotic cardiovascular disease and/or ischemia, and not HF generally. 5.2. Preventing SCD With HF Medications Recommendation for Pharmacological Prevention of SCD References that support the recommendation are summarized in Online Data Supplement 10. COR LOE Recommendation I A In patients with HFrEF (LVEF 40%), treatment with a beta blocker, a mineralocorticoid receptor antagonist and either an angiotensin-converting enzyme inhibitor, an angiotensin-receptor blocker, or an angiotensin receptor-neprilysin inhibitor is recommended to reduce SCD and all-cause Recommendation-Specific Supportive Text 1. For patients with HF and depressed LV func- tion, appropriate medical therapy is important to reduce SCD. These therapies have various beneficial effects on arrhythmia mechanisms. Beta blockers reduce myocardial oxygen demand and electrical excitability, and counter arrhyth- mogenic effects of sympathetic stimulation. 