Influence of Aging on Outcomes of Sacubitril/Valsartan in Hypertensive Patients with Heart Failure: A Multicenter Retrospective Study.

BACKGROUND: The aim of this study was to investigate the influence of aging on the effectiveness and tolerance of sacubitril/valsartan (sac/val) among hypertensive patients complicated with heart failure in a real-world setting. METHODS: This multicenter, retrospective study included patients (≥18 years old) admitted with a diagnosis of hypertension and heart failure, starting sac/val therapy between January 2020 and December 2021 from 3 medical centers. Patients were grouped by the cutoff age of 65 years. Outcomes were collected 31-365 days after the initiation of sac/val and were compared in a matched cohort after 1: 1 propensity score matching (PSM). RESULTS: A total of 794 patients were finally analyzed. Blood pressure and cardiac functions improved significantly compared with values at baseline. There were 269 patients in each cohort (<65 years and ≥65 years) after PSM. After PSM, the incidence of hyperuricemia and hypotension in the elderly patients (≥65 years) was significantly higher than in those <65 years of age. Kaplan-Meier estimate suggested that the cumulative incidence of new or recurrent cardiovascular events increased significantly at the age of ≥65 years after the point of 3 months (log-rank P =.00087). CONCLUSION: Sac/val benefited patients in both cohorts by improving blood pressure and cardiac function. Elderly patients (≥65 years) were susceptible to hypotension, low diastolic blood pressure, hyperuricemia, and underwent cardiac-related readmissions more frequently.

Effectiveness and safety evaluation of sacubitril/valsartan in blood pressure control and clinical outcomes for elderly patients with heart failure and hypertension: A prospective cohort study.

AIM: This study was conducted to investigate the safety and effectiveness of sacubitril/valsartan (sac/val) for elderly patients with hypertension and heart failure in the real-world setting. METHODS: Patients with established hypertension complicated with structural or functional impairment of ventricular fillings [New York Heart Association (NYHA) functional class II-IV)] were enrolled. The effectiveness of sac/val in terms of BP reduction and improvement in frailty and echocardiographic evaluation of cardiac function were examined from baseline to 6-month administration. RESULTS: Overall, 241 patients were treated with sac/val and 227 with renin angiotensin aldosterone system inhibitor (RAASi) for hypertension control. There were significant difference in the degree of systolic blood pressure reduction between two groups. Echocardiography showed that sac/val significantly improved left ventricular ejection fraction [4.0% (95% CI: 2.0-7.5) vs -1.0 (95% CI: -4.0-2.0), P = 0.001] during the follow-up visits. Significant improvements in NYHA function class and FRAIL scores post sac/val were observed after 3 and 6 month treatment. The rate of primary cardiovascular composite outcome was higher in patients in the RAASi group (26.9%; 95% CI: 19.6-34.0) than in the sac/val group (22.0%; 95% CI: 16.7-27.3). CONCLUSIONS: Sac/val may be useful not only for reducing BP, but also for improving the structural and functional parameters of echocardiography, eventually resulting in a significant improvement of the overall symptomatic status, a significant reduction in NYHA class, and functional improvement.

A Novel Biomarker Scoring System Alone or in Combination with the GRACE Score for the Prognostic Assessment in Non-ST-Elevation Myocardial Infarction.

Purpose: The Global Registry of Acute Coronary Events (GRACE) score has proven value in predicting short-term prognosis in non-ST-elevation myocardial infarction (NSTEMI), but it has only moderate discrimination for long-term outcomes. The purpose of this study is to develop and test a multi-biomarker score for better risk stratification and indication of 2-year risk in patients with NSTEMI. Patients and Methods: A total of 6076 consecutive patients with NSTEMI (66 [59-73] years, 73.1% males) admitted at Zhongshan Hospital, Fudan University were collected in this observational, prospective study between 2012 and 2018 with a 24-month follow-up. The primary endpoint was all-cause death and non-fatal major adverse cardiac events (MACE). A biomarker score ranged from 0 to 12 was constructed. The predictive power of the biomarker score was evaluated alone or combined with the GRACE score by C-statistic, net reclassification index (NRI) and integrated discrimination index (IDI). Results: During a 2-year follow-up, all-cause death occurred in 159 patients (2.6%), and non-fatal MACEs were presented in 709 patients (11.7%). When added to the GRACE score, the biomarker score demonstrated better prognostic accuracy, patient reclassification and risk discrimination for both mortality and non-fatal MACEs at 2 years by improving the C-statistic from 0.714 (0.671-0.756) and 0.623 (0.600-0.646) to 0.851 (0.820-0.882) and 0.721 (0.702-0.741) with NRI >25% (P<0.001) and IDI >0.30 (P<0.001). Conclusion: The single use of biomarker score could markedly enhance the prognostic value of concurrent risk stratification tools for 2-year mortality and non-fatal MACEs in NSTEMI. The GRACE score with incorporation of the biomarker score led to more accurate risk reclassification and warrants more consideration in further NSTEMI management.

Effectiveness and safety of sacubitril/valsartan for patients with hypertension and heart failure in the real-world setting: A retrospective study in China.

WHAT IS KNOWN AND OBJECTIVE: Hypertension (HP) is associated with heart failure (HF). Sacubitril/valsartan (sac/val) has been approved for primary HP by China Food and Drug Administration (CFDA) in June 2021. The present study aimed to provide evidence on the effectiveness and safety of sac/val in Chinese patients complicated with HP and HF. METHODS: This retrospective study was conducted on adult patients diagnosed with HP and HF and treated with sac/val between July 2020 and December 2020. The potential risk factors for the discontinuation events caused by sac/val-related adverse events (AEs) were explored. The data, including blood pressure (BP), cardiac indicators, corresponding values on echocardiographic parameters, unplanned visits, and AEs throughout 3-12 months, were collected. RESULTS AND DISCUSSION: A total of 446 eligible patients were included in this study. The discontinuation events of sac/val were mainly attributed to its AEs (hypotension, hyperkalemia, and deterioration in kidney function). Univariate analysis revealed that history of chronic kidney disease, atrial fibrillation, higher values of serum creatinine, serum uric acid, serum N-terminal pro B-type natriuretic peptide, and lower estimated glomerular filtration rate were potential risk factors for discontinuation. Patients who maintained sac/val therapy throughout 3-12 months showed significantly improved values of clinical BP, cardiac indicators, and echocardiographic parameters compared to those at baseline (p < 0.0001). WHAT IS NEW AND CONCLUSION: Sac/val was effective on BP and improved cardiac function in patients complicated with HP and HF. The physicians should focus on patients with renal dysfunction to take timely precautions to improve tolerability for sac/val.

Evaluation of pharmacist-led telemedicine medication management for hypertension established patients during COVID-19 pandemic: A pilot study.

Aim: To evaluate the impact of a telemedicine medication management service in patients with hypertension. Methods: Participants were allocated to either a telemedicine service (N = 173) or usual care (UC) (N = 179). The primary outcome was blood pressure (BP) reduction from baseline to the 6-month follow-up visit, the proportion of the target BP achievement, overall adherence to prescribed medication as well as a composite of non-fatal stroke, non-fatal myocardial infarction and cardiovascular death. Results: At 6 months, BP was controlled in 89.6% (n = 155) of intervention patients and 78.8% (n = 141) of UC patients (OR = 1.14, 95% CI = 1.04-1.25, P = 0.006), giving a mean difference of -6.0 (-13.0 to -2.5 mmHg) and -2.0 mmHg (-4.0 to -0.1 mmHg) in SBP and DBP, respectively. 17.9% (n = 31) of the patients in the intervention group were non-adherent with medications, compared with 29.1% (n = 52) in the UC group (P = 0.014). The composite clinical endpoints were reached by 2.9% in the intervention group and 4.5% in the control group with no significant differences (OR = 1.566, 95% CI = 0.528-4.646). Conclusion: Telemedicine medication management for hypertension management had led to better BP control and medication adherence improvement than UC during COVID-19 epidemic, resulting in a reduction of overall adverse cardiovascular events occurrence.

Impact of Renal Function on Effectiveness and Safety Associated With Low Dose Dabigatran in Non-valve Atrial Fibrillation Patients After Catheter Ablation.

Aim: The purpose of this study is to compare the effectiveness and safety of 110 mg dabigatran in non-valve atrial fibrillation (NVAF) patients with different eGFRs. Methods: We conducted a single-center retrospective cohort study to investigate the effectiveness and safety of 110 mg dabigatran for NVAF patients between January 2017 and December 2018 based on the eGFR category. Results: A total of 560 NVAF patients who treated with 110 mg dabigatran were included for analysis. In 12 months, the Kaplan-Meier survival curves indicated that the lower eGFR subgroups were more likely to experience thrombosis, bleeding, and cumulative events earlier (P = 0.021 for thrombosis; P = 0.026 for bleeding; P = 0.001 for cumulative events). Gastrointestinal bleeding occurred more frequently in the moderate group than in other groups (6.94% in the moderate group vs. 1.54% in the mild group vs. 1.22% in the normal group, P = 0.028). By multivariate analysis, chronic kidney disease (P = 0.043; OR = 4.273, 95% CI 1.043-17.543) and diabetes mellitus (P = 0.023; OR = 2.194, 95% CI 1.114-4.323) were independent predictors of the composite endpoints. A positive linear relationship was observed between eGFR levels and occurrence rate of thrombosis and bleeding under anticoagulation patients with 110 mg dabigatran (R 2 = 0.432 and R 2 = 0.784, respectively). Conclusions: Impaired renal function was associated with decreased safety and increased thrombosis risks in NVAF patients taking low dose dabigatran.

Real-World Data of Tigecycline-Associated Drug-Induced Liver Injury Among Patients in China: A 3-year Retrospective Study as Assessed by the Updated RUCAM.

Background: Tigecycline, a glycylcycline antibiotic, is increasingly used clinically for the treatment of severe infections caused by multidrug-resistant bacteria, but it is also associated with hepatotoxicity. However, the incidence and risk factors of tigecycline-associated drug-induced liver injury (DILI) are unclear. We conducted this study to investigate the incidence, characteristics and risk factors of tigecycline-associated DILI in the real-world clinic setting. Patients and Methods: A retrospective analysis was conducted in inpatients who received tigecycline treatment from January 2018 to January 2020. Based on the biochemical criteria of DILI and the causality assessment by Roussel Uclaf Causality Assessment Method (RUCAM) using cases with a probable or highly probable causality grading, two clinical pharmacists and one clinician worked together to screen patients for tigecycline-associated DILI. Then patients with DILI were randomly matched by gender in a ratio of 1:2 to the remaining patients in the tigecycline cohort without biochemical abnormalities to identify risk factors. Results: A total of 973 patients from 1,250 initial participants were included. The incidence of tigecycline-associated DILI was 5.7% (55/973). Among 55 DILI patients, 10 cases presented with the hepatocellular pattern, 4 cases belonged to the mixed pattern, and 41 presented with the cholestatic pattern. Most cases reached the severity of grade 1 and 2. The rate of recovery in hepatocellular pattern, mixed pattern, and cholestatic pattern was 70.0, 50.0, and 41.5%, respectively. The proportion of the DILI cases treated with high dose (100 mg) and prolonged duration (>14 days) was significantly higher than standard dose and routine duration (100.0% vs. 18.1%, p < 0.05). Logistic regression analysis showed that high maintenance dose (OR = 1.028, p = 0.002), prolonged duration (OR = 1.208, p = 0.000), and number of hepatotoxic drugs (OR = 2.232, p = 0.000) were independent factors of tigecycline-associated DILI. Conclusion: Tigecycline was associated with liver injury, with a slightly higher incidence (5.7%) than the frequency of "frequent" (5%) defined by the Medical Dictionary for Regulatory Activities. Patients with a high maintenance dose and prolonged tigecycline regimen, as well as concomitant use of multiple hepatotoxic drugs should be paid more attention.

Body Mass Index Influence on the Clinical Outcomes for Nonvalvular Atrial Fibrillation Patients Admitted to a Hospital Treated with Direct Oral Anticoagulants: A Retrospective Cohort Study.

BACKGROUND: Considering that the current fixed dose of direct oral anticoagulants (DOACs) might have insufficient anticoagulation effect for overweight patients, the aim of this study was to compare the effectiveness and safety of anticoagulation between dabigatran and rivaroxaban in different body mass index (BMI) population. METHODS: We conducted a retrospective cohort study of 2402 DOAC anticoagulated patients with atrial fibrillation who underwent catheter ablation (1290 dabigatran, 53.7% and 1112 rivaroxaban, 46.3%) between January 2017 and December 2018. Patients were distributed based on the BMI into nonobese (1362, BMI <25 kg/m2), preobese (521, BMI 25.0-29.9 kg/m2), class I obese (344, BMI 30.0-34.9 kg/m2) and class II+ obese (175, BMI ≥35.0 kg/m2). We collected information regarding clinical features, laboratory data, bleeding complications and systemic embolic events from the electrical medical records system during 12 months. RESULTS: The incidence of systemic embolism and stroke complications was higher in the class II+ obese group (P=0.001 and P=0.003). The incidence of bleeding complications and the levels of anticoagulation parameters under the bleeding threshold were similar among the four groups (P>0.05). Cumulative Kaplan-Meier analysis illustrated that rivaroxaban-treated patients who belonged to higher BMI subgroups were more likely to experience shorter time to thrombosis (TTT) (12-month TTT rates of 0.5% for nonobese vs 1.7% for class I obese patients, HR=3.716, P=0.005; 12-month TTT rates of 0.5%, for nonobese vs 4.0% for class II+ obese patients, HR=6.843, P=0.001). However, no statistical significant difference in terms of the time to bleeding complications and the time to cumulative events among the four groups was observed. By multivariate analysis, a higher BMI value (BMI ≥25 kg/m2) (P=0.019; OR=2.094, 95%CI: 1.129-3.883) was an independent predictor for thrombosis in patients treated with dabigatran or rivaroxaban. Positive linear relationship was observed between BMI levels and occurrence rate of thrombosis and bleeding in under anticoagulation patients with NVAF (R2=0.451 and R2=0.383, respectively). CONCLUSION: The fixed dose of 15 mg rivaroxaban might carry a risk of under exposure, which would lead to an increase of thromboembolic complications in patients with high BMI. Therefore, rivaroxaban dose increase was suggested for obese patients. Use of DOACs appears to have considerable safety in obese patients.

Evaluation of Remote Pharmacist-Led Outpatient Service for Geriatric Patients on Rivaroxaban for Nonvalvular Atrial Fibrillation During the COVID-19 Pandemic.

OBJECTIVE: This study was designed to evaluate the efficacy of remote medication management of rivaroxaban by pharmacists for geriatric patients with nonvalvular atrial fibrillation during the COVID-19 pandemic. METHODS: A single-site, prospective cohort study was conducted among patients with non-valvular atrial fibrillation who received rivaroxaban therapy from July 2019 to December 2019. Patients in the pharmacist-led education and follow-up service (PEFS) group were managed remotely by a pharmacist. In contrast, those in the usual care (UC) group were managed by other providers. Data of routine blood tests, coagulation function tests, which also included cardiac function parameters were collected. The number and type of provider encounters, interventions related to rivaroxaban therapy, the occurrence of thromboembolism or bleeding, and the time of the first outpatient visit after discharge were recorded. RESULTS: A total of 600 patients were recruited, and results of 381 patients were analyzed in the end, of which 179 patients were from the PEFS group and 202 were from the UC group. There was no significant difference between the two groups in terms of the occurrence ratio of systemic thrombosis, heart failure (LVEF < 40%), and left atrial dilation, which was defined as enlargement of left atrial diameter (LAD) > 40 mm. The cumulative incidences of bleeding complications, such as gastrointestinal tract and skin ecchymosis, were significantly higher in the UC group (12.4% vs. 6.1%, P=0.038; 4.5% vs. 0.6%, P=0.018). There was no significant difference after pharmacist intervention in terms of thrombosis occurrence ratio between the two groups (P = 0.338, HR: 0.722, 95% CI: 0.372-1.405). Remote instruction by a pharmacist reduced outpatient service frequency within the first 30 days after discharge (23.7% vs. 1.1%, P < 0.001). However, more patients in the PEFS group presented for the first outpatient revisit later than 40 days post-discharge (12.8% vs. 21.3%, P < 0.001). CONCLUSION: Remote pharmacist-led medication instruction of rivaroxaban could reduce bleeding complications of the gastrointestinal tract and skin ecchymosis and postpone the first outpatient revisit after discharge.