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Aims Sudden death is a leading cause of mortality in heart failure with reduced ejection fraction (HFrEF). In PARADIGM-HF, sacubitril/valsartan reduced the incidence of sudden death. The purpose of this post hoc study was to analyse the effect of sacubitril/valsartan, compared to enalapril, on the incidence of ventricular arrhythmias. Methods and results Adverse event reports related to ventricular arrhythmias were examined in PARADIGM-HF. The effect of randomized treatment on two arrhythmia outcomes was analysed: ventricular arrhythmias and the composite of a ventricular arrhythmia, implantable cardioverter defibrillator (ICD) shock or resuscitated cardiac arrest. The risk of death related to a ventricular arrhythmia was examined in time-updated models. The interaction between heart failure aetiology, or baseline ICD/cardiac resynchronization therapy-defibrillator (CRT-D) use, and the effect of sacubitril/valsartan was analysed. Of the 8399 participants, 333 (4.0%) reported a ventricular arrhythmia and 372 (4.4%) the composite arrhythmia outcome. Ventricular arrhythmias were associated with higher mortality. Compared with enalapril, sacubitril/valsartan reduced the risk of a ventricular arrhythmia (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.62-0.95; p = 0.015) and the composite arrhythmia outcome (HR 0.79, 95% CI 0.65-0.97; p = 0.025). The treatment effect was maintained after adjustment and accounting for the competing risk of death. Baseline ICD/CRT-D use did not modify the effect of sacubitril/valsartan, but aetiology did: HR in patients with an ischaemic aetiology 0.93 (95% CI 0.71-1.21) versus 0.53 (95% CI 0.37-0.78) in those without an ischaemic aetiology (p for interaction = 0.020). Conclusions Sacubitril/valsartan reduced the incidence of investigator-reported ventricular arrhythmias in patients with HFrEF. This effect may have been greater in patients with a non-ischaemic aetiology. [ABSTRACT FROM AUTHOR]

Aims: Recurrent hospitalizations are a major part of the disease burden in heart failure (HF), but conventional analyses consider only the first event. We compared the effect of sacubitril/valsartan vs. enalapril on recurrent events, incorporating all HF hospitalizations and cardiovascular (CV) deaths in PARADIGM-HF, using a variety of statistical approaches advocated for this type of analysis.Methods and Results: In PARADIGM-HF, a total of 8399 patients were randomized and followed for a median of 27 months. We applied various recurrent event analyses, including a negative binomial model, the Wei, Lin and Weissfeld (WLW), and Lin, Wei, Ying and Yang (LWYY) methods, and a joint frailty model, all adjusted for treatment and region. Among a total of 3181 primary endpoint events (including 1251 CV deaths) during the trial, only 2031 (63.8%) were first events (836 CV deaths). Among a total of 1195 patients with at least one HF hospitalization, 410 (34%) had at least one further HF hospitalization. Sacubitril/valsartan compared with enalapril reduced the risk of recurrent HF hospitalization using the negative binomial model [rate ratio (RR) 0.77, 95% confidence interval (CI) 0.67-0.89], the WLW method [hazard ratio (HR) 0.79, 95% CI 0.71-0.89], the LWYY method (RR 0.78, 95% CI 0.68-0.90), and the joint frailty model (HR 0.75, 95% CI 0.66-0.86) (all P < 0.001). The effect of sacubitril/valsartan vs. enalapril on recurrent HF hospitalizations/CV death was similar.Conclusions: In PARADIGM-HF, approximately one third of patients with a primary endpoint (time-to-first) experienced a further event. Compared with enalapril, sacubitril/valsartan reduced both first and recurrent events. The treatment effect size was similar, regardless of the statistical approach applied. [ABSTRACT FROM AUTHOR]

Question In Chinese adults with hypertension, does enalapril plus folic acid reduce incident stroke more than enalapril alone? Methods Design Randomized controlled trial (China Stroke Primary Prevention Trial [CSPPT]). ClinicalTrials.gov NCT00794885. Trial was stopped early for efficacy. Allocation Concealed.* Blinding Blinded* (patients, investigators, outcome and data assessors, monitoring committee). Follow-up period Median 4.5 years. Setting 32 communities in Jiangsu and Anhui provinces, China. Patients 20 702 patients 45 to 75 years of age (mean age 60 y, 59% women) who had hypertension (seated resting systolic blood pressure [BP] ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg at screening and recruitment visits or were receiving antihypertensive medication) and good adherence to oral enalapril, 10 mg/d, during a 3-week run-in phase. Exclusion criteria included previous stroke, myocardial infarction (MI), heart failure, coronary revascularization, or congenital heart disease. Intervention Combination pill of oral enalapril, 10 mg/d, plus folic acid, 0.8 mg (n = 10 348), or oral enalapril, 10 mg/d, alone (n = 10 354). Concomitant use of other antihypertensive drugs (except B vitamins) was permitted. Outcomes Primary outcome was first stroke (fatal or nonfatal, ischemic or hemorrhagic). Secondary outcomes included a composite of cardiovascular (CV) events (stroke, CV death, or MI), components of the composite outcome, and all-cause death. Patient follow-up 99.7% (intention-to-treat analysis). Main results The main results are in the Table. Conclusion In Chinese adults with hypertension, enalapril plus folic acid reduced incident stroke more than enalapril alone. [ABSTRACT FROM AUTHOR]

Provides information on a study which reported the case of a 23 year old patient who developed pancreatitis while receiving enalapril for hypertension. Overview of cases related to the use of enalapril; Steps taken in an attempt to link enalapril and pancreatitis; Speculation on the influence of angiotensin-converting enzyme inhibitors on pancreatic cells.