Rozibafusp alfa (AMG 570) is a first‐in‐class bispecific IgG2‐peptide fusion designed to inhibit inducible T‐cell costimulator ligand (ICOSL) and B‐cell activating factor (BAFF). The pharmacokinetics (PK) and pharmacodynamics (PD) of rozibafusp alfa were investigated in two randomized, placebo‐controlled clinical studies: a phase Ia single ascending‐dose study (7–700 mg subcutaneously (s.c.)) in healthy subjects and a phase Ib multiple ascending‐dose study (70–420 mg s.c. every 2 weeks (q2w)) in patients with rheumatoid arthritis. Rozibafusp alfa exhibited nonlinear PK and dose‐related and reversible dual‐target engagement. Maximal reduction of naïve B cells from baseline (> 40%), reflective of BAFF inhibition, was achieved with rozibafusp alfa exposure (area under the concentration‐time curve from time 0 to time infinity (AUC_inf) and AUC within a dosing interval from day 0 to day 14 (AUC_tau)) above 51 and 57 days•μg/mL for the single‐dose (≥ 70 mg) and multiple‐dose studies (≥ 70 mg q2w), respectively. ICOSL receptor occupancy on circulating B cells, a surrogate PD end point for ICOSL inhibition, was directly related to drug concentration. PK/PD analysis showed > 90% RO at rozibafusp alfa ≥ 22.2 μg/mL (≥ 420‐mg single dose or ≥ 210 mg q2w multiple dose), with saturation occurring at higher drug concentrations. These results informed the design and dose selection of a phase IIb study assessing the safety and efficacy of rozibafusp alfa in patients with active systemic lupus erythematosus.

Previous studies found that cilostazol has a favorable effect on glucose and lipid homeostasis, endothelial function, atherosclerosis, and vasculo-angiogenesis. However, it is poorly understood whether these effects can translate into better clinical outcomes. This study investigated the outcome effect of cilostazol in patients with coronary artery disease (CAD) or at a high risk of cardiovascular (CV) disease. We conducted a randomized, double-blind, placebo-controlled trial involving 266 patients who received cilostazol, 200 mg/day (n = 134) or placebo (n = 132). Pre-specified clinical endpoints including composite major adverse cardiovascular events (MACE) (CV death, non-fatal myocardial infarct, non-fatal stroke, hospitalization for heart failure, or unplanned coronary revascularization), the composite major coronary event (MCE) and major adverse CV and cerebrovascular event (MACCE), were prospectively assessed. The mean duration of follow-up was 2.9 years. Relative to placebo, cilostazol treatment had a borderline effect on risk reduction of MACE (hazard ratio [HR], 0.67; 95% confidence interval (CI), 0.34–1.33), whereas the beneficial effect in favor of cilostazol was significant in patients with diabetes mellitus or a history of percutaneous coronary intervention (p for interaction, 0.02 and 0.06, respectively). Use of cilostazol, significantly reduced the risk of MCE (HR, 0.38; 95% CI, 0.17–0.86) and MACCE (HR, 0.47; 95% CI, 0.23–0.96). A significantly lower risk of angina pectoris (HR, 0.38; 95% CI, 0.17–0.86) was also observed in the cilostazol group. After multi-variable adjustment, cilostazol treatment independently predicted a lower risk of MCE. In conclusion, these results suggest cilostazol may have beneficial effects in patients with CAD or at a high risk of CV disease.

Atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease, cerebrovascular disease, and peripheral artery disease, carries a high morbidity and mortality. Risk factor control is especially important for patients with ASCVD to reduce recurrent cardiovascular events. Clinical guidelines have been developed by the Taiwan Society of Cardiology, Taiwan Society of Lipids and Atherosclerosis, and Diabetes Association of Republic of China (Taiwan) to assist health care professionals in Taiwan about the control of hypertension, hypercholesterolemia and diabetes mellitus. This article is to highlight the recommendations about blood pressure, cholesterol, and sugar control for ASCVD. Some medications that are beneficial for ASCVD were also reviewed. We hope the clinical outcomes of ASCVD can be improved in Taiwan through the implementation of these recommendations.

Background: P2Y12 inhibitor monotherapy is an alternative antiplatelet strategy in patients undergoing percutaneous coronary intervention (PCI). However, the ideal P2Y12 inhibitor for monotherapy is unclear. Methods and Results: We performed a multicenter, retrospective, observational study to compare the efficacy and safety of monotherapy with clopidogrel versus ticagrelor in patients with acute coronary syndrome (ACS) undergoing PCI. From 1 January 2014 to 31 December 2018, 610 patients with ACS who received P2Y12 monotherapy with either clopidogrel (n = 369) or ticagrelor (n = 241) after aspirin was discontinued prematurely were included. Inverse probability of treatment weighting was used to balance covariates between the groups. The primary endpoint was the composite of all-cause mortality, recurrent ACS or unplanned revascularization, and stroke within 12 months after discharge. Overall, 84 patients reached the primary endpoint, with 57 (15.5%) in the clopidogrel group and 27 (11.2%) in the ticagrelor group. Multivariate adjustment in Cox proportional-hazards models revealed a lower risk of the primary endpoint with ticagrelor than with clopidogrel (adjusted hazard ratio (aHR): 0.67, 95% confidence interval (CI): 0.49–0.93). Ticagrelor significantly reduced the risk of recurrent ACS or unplanned revascularization (aHR: 0.46, 95% CI: 0.28–0.75). No significant difference in all-cause mortality and major bleeding events was observed between the 2 groups. Conclusions: Among patients with ACS undergoing PCI who cannot complete course of dual antiplatelet therapy, a significantly lower risk of cardiovascular events was associated with ticagrelor monotherapy than with clopidogrel monotherapy. The major bleeding risk was similar in both the groups.

Background: Despite a preferred endocrine therapy for women with estrogen and progesterone receptor-positive breast cancer, aromatase inhibitors (AIs) have been reported to increase risks of cardiovascular events. Given that breast cancer patients in Asia are younger at diagnosis, it is urgent to investigate this safety concern. Methods: Through the Taiwanese National Cohort, we identified breast cancer patients initiating selective estrogen receptor modulators (SERMs) or AIs from 2010 to 2016. Outcomes includes major adverse cardio- and cerebrovascular events (MACCEs). The average follow-up duration was five years. Results: We identified 16,730 breast cancer patients treated with SERMs and 11,728 receiving AIs. The population was older and had more comorbidities in the AI group than in the SERM group. After adjusting for age, cancer stage, cancer therapies, cardiovascular drugs and comorbidities, despite similar risks of MACCEs between AI and SERM users, the risk of HF was significantly higher in patients treated with SERMs after adjusted mortality as a competing risk. When divided by the age of 50 years, despite a similar MACCEs in the younger population, MACCEs remained significantly higher in the older population who received SERMs. Conclusions: In this Asian cohort, we found that among patients of old age or with advanced cancer stage, the use of SERMs was associated with a higher risk of cardiovascular events than the use of AIs.

Rationale: Sodium polystyrene sulfonate is commonly administered to treat hyperkalemia. Severe pneumonia due to aspiration of this drug is rare and no survival case has thus far been reported. Patient concerns: A 45-year-old man was hospitalized for acute decompensated heart failure and acute kidney injury with hyperkalemia. He aspirated sodium polystyrene sulfonate while consuming the drug. Severe acute respiratory distress syndrome (ARDS) developed rapidly, and he was transferred to the intensive care unit (ICU). Diagnoses: Chest radiography results after aspiration showed new consolidation in the left upper lung. He underwent emergency bronchoscopy, which revealed a considerable amount of yellow mud-like material in the trachea and bronchi. Chest radiography results after the bronchoscopic removal of the foreign material revealed rapid resolution of the left upper lung consolidation. Interventions: In the ICU, mechanical ventilation with low tidal volume and high positive end-expiratory pressure was administered and extracorporeal membrane oxygenation (ECMO) was set up for treating severe ARDS. We arranged an emergency bronchoscopy for diagnosis and removal of polystyrene sulfonate. Outcomes: ECMO was discontinued after 10 days and the patient was discharged after approximately 2 weeks. Lessons: Aspiration of sodium polystyrene sulfonate is not common but can be lethal. Clinicians should be cautious and appropriately inform patients of the aspiration risk while administering this drug. Mechanical ventilation and bronchoscopy were effective treatments for severe ARDS caused by aspiration of this drug.