Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

BACKGROUN

Impact of chronic coronary syndromes on cardiovascular hospitalization and mortality: the ESC-EORP CICD-LT registry

Abstract Aims In Europe, global data on guideline adherence, geographic variations, and determinants of clinical events in patients with chronic coronary syndrome (CCS) remain suboptimal. The European Society of Cardiology (ESC) EURObservational Research Programme (EORP) Chronic Ischemic Cardiovascular Disease Long-Term (CICD-LT) registry is a prospective European registry, and was designed to describe the profile, management, and outcomes of patients with CCS across the ESC countries. Methods and results We aimed to investigate clinical events at 1-year follow-up from the ESC EORP CICD-LT registry. One-year outcomes of 6655 patients from the 9174 recruited in this European registry were analysed. Overall, 168 patients (2.5%) died, mostly from cardiovascular (CV) causes (n = 97, 1.5%). Northern Europe had the lowest CV mortality rate, while southern Europe had the highest (0.5 vs. 2.0%, P = 0.04). Women had a higher rate of CV mortality compared with men (2.0 vs. 1.3%, P = 0.02). During follow-up, 1606 patients (27.1%) were hospitalized at least once, predominantly for CV indications (n = 1220, 20.6%). Among the population with measured low-density lipoprotein-cholesterol level at 1 year, 1434 patients (66.5%) were above the recommended target. Age, history of atrial fibrillation, previous stroke, liver disease, chronic obstructive pulmonary disease or asthma, increased serum creatinine, and impaired left ventricular function were associated with an increased risk of CV death or hospitalization. Conclusion In the CICD registry, the majority of patients with CCS have uncontrolled CV-risk factors. The 1-year mortality rate is low, but these patients are frequently hospitalized for CV causes. Early identification of comorbidities may represent an opportunity for enhanced care and better outcomes. </jats:sec

Cohort profile. the ESC-EORP chronic ischemic cardiovascular disease long-term (CICD LT) registry

The European Society of cardiology (ESC) EURObservational Research Programme (EORP) Chronic Ischemic Cardiovascular Disease registry Long Term (CICD) aims to study the clinical profile, treatment modalities and outcomes of patients diagnosed with CICD in a contemporary environment in order to assess whether these patients at high cardiovascular risk are treated according to ESC guidelines on prevention or on stable coronary disease and to determine mid and long term outcomes and their determinants in this population

The ESC-EORP Chronic Ischaemic Cardiovascular Disease Long Term (CICD LT) registry

Abstract Aims The European Society of Cardiology (ESC) EURObservational Research Programme (EORP) Chronic Ischaemic Cardiovascular Disease Long Term (CICD LT) registry aims to study the clinical profile, treatment modalities, and outcomes of patients diagnosed with CICD in a contemporary environment in order to assess whether these patients at high cardiovascular (CV) risk are treated according to ESC guidelines on prevention or on stable coronary disease and to determine mid- and long-term outcomes and their determinants in this population. Methods and results Nine thousand one hundred and seventy-four patients over 18 years with documented CICD defined by a history acute coronary syndrome with/without ST elevation, previous coronary revascularization, or stable coronary artery disease were enrolled between 1 May 2015 and 31 July 2018. Individual patient data on clinical profile, biology, and treatment modalities were collected across 154 centres from 20 ESC countries. Two years of follow-up is scheduled in order to determine the following clinical outcomes: all-cause and CV death, all-cause and CV hospitalizations, changes in medications, and quality of life using the EuroQol5D-5L score. Conclusion The CICD LT is an international registry of care and outcomes of patients hospitalized with CICD which will provide insights into the contemporary profile and management of patients with this common disease. </jats:sec

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin- kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. RESULTS At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P = 0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P = 0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P = 0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001). CONCLUSIONS In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients