European Heart Journal - Cardiovascular Pharmacotherapy最新文献

Aims: To evaluate the risk of incident dementia associated with sacubitril/valsartan in patients with heart failure (HF) in South Korea.

Methods and results: We conducted a retrospective cohort study using the National Health Insurance Database in South Korea. Patients diagnosed with HF and prescribed either sacubitril/valsartan or angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) within 90 days of their first HF diagnosis between October 2017 and December 2020 were included. The primary outcome was incident dementia, categorized into Alzheimer's dementia and vascular dementia. Follow-up began after 1 year from the prescription date, to accommodate dementia onset latency, until the earliest occurrence of dementia, death, or end of study period (March 2023). After 1:4 propensity score matching, the hazard ratio (HR) with 95% confidence interval (CI) for dementia was estimated using a Cox proportional hazards model. Among 7085 sacubitril/valsartan users and 359 153 ACEI/ARB users, 6930 sacubitril/valsartan users [mean (SD) age, 61.7 (14.6) years; 70.9% male] were matched on propensity score to 27 720 ACEI/ARB users [mean (SD) age, 61.7 (15.8) years; 71.1% male]. During a mean follow-up of 2.2 and 2.3 years, dementia occurred in 200 (2.9%) sacubitril/valsartan users and 980 (3.5%) ACEI/ARB users, respectively. Sacubitril/valsartan showed a 16% lower risk of dementia compared with ACEI/ARB (HR 0.84; 95% CI 0.72-0.98). However, of 1180 cases of incident dementia, 1079 (91.4%) were categorized as Alzheimer's dementia and statistical significance was not reached in this main group.

Conclusion: Despite plausible biological mechanisms, no association between sacubitril/valsartan and an increased risk of dementia was observed in patients with HF.

Aims: The ability of sodium-glucose co-transporter 2 (SGLT2) inhibitors to prevent atrial fibrillation (AF) has been evaluated in various studies with conflicting results. This study aimed to determine whether SGLT2 inhibitors have a protective effect against AF depending on the baseline clinical condition in which the randomized controlled trials (RCTs) were conducted.

Methods and results: A trial-level meta-analysis was performed including 52 RCTs (112 031 patients) comparing SGLT2 inhibitors with placebo and reporting the number of patients who developed AF in each arm. Risk ratios (RRs) for AF development with 95% confidence intervals (95% CIs) were pooled using a random-effects model. Subgroup analyses were performed by classifying RCTs according to the inclusion criteria of each trial [diabetes, chronic kidney disease, heart failure with reduced ejection fraction (HFrEF), mildly reduced EF (HFmrEF), and preserved EF (HFpEF)]. Overall, SGLT2 inhibitors prevented AF (RR = 0.86, 95% CI 0.77-0.96). In the subgroup analysis, the AF-preventive ability of SGLT2 inhibitors was influenced by HF, being preserved in RCTs recruiting 9141 patients with HFrEF, but not in those recruiting 12 877 subjects with HFmrEF/HFpEF (P-value for group difference = 0.01). Meta-regression showed a reduced efficacy of SGLT2 inhibitors in preventing AF when more patients with hypertension or higher EF were enrolled (P < 0.01 for both).

Conclusion: Sodium-glucose co-transporter 2 inhibitors prevent AF. Their protective effect was confirmed in the HFrEF subgroup, but not in RCTs recruiting patients with HFmrEF/HFpEF, possibly indicating a different pathophysiology leading to AF among these conditions. However, given the limitations of a trial-level analysis, these findings are exploratory, pending confirmation from patient-level data.

Aims: Whether the adoption of CHA2DS2-VA score, the sex-independent version of the CHA2DS2-VASc score is beneficial for stratifying risk of stroke in patients with atrial fibrillation (AF) remains controversial.

Methods and results: Utilizing the data from the global, multicentre and prospective GLORIA-AF Registry Phase III, we compared the performances of CHA2DS2-VA and CHA2DS2-VASc scores in stratifying the risk of ischaemic stroke and thromboembolism (TE), and compared the risk of ischaemic stroke and TE, and the use of oral anticoagulants in male and female patients with AF. A total of 21 260 AF patients with available data were included in the analysis (mean age 70.2 ± 10.3 years, 44.9% female). Overall, female patients were less likely prescribed with oral anticoagulant (OAC) compared with males [odds ratio: 0.90, 95%confidence interval [CI]: (0.83-0.97)]. A significant interaction (P < 0.001) between sex and age was observed, with a lower likelihood of receiving OAC among younger female patients.The risk of ischaemic stroke [hazard ratio (HR):1.14, 95%CI: (0.85-1.53)] and TE [HR: 1.02, 95%CI: (0.82-1.26)] was similar between male and female patients, and the predictive ability of the two scores was similar for both outcomes: TE [area under the receiver operating characteristic curve (AUC): 0.641, 95%CI: (0.585-0.697) vs. AUC: 0.636, 95%CI: (0.580-0.692); P = 0.593] and ischaemic stroke [AUC: 0.660, (95%CI: 0.582-0.739) vs. AUC: 0.646, (95%CI: 0.568-0.725); P = 0.847]. There was a possible interaction between sex and age observed, with a higher risk of TE in younger female patients (P = 0.051).

Conclusion: CHA2DS2-VA score had similar predictive performance for thromboembolic events compared with CHA2DS2-VASc score. The role of female sex in the management and outcomes of patients with AF may differ according to age. Whether the omission of the female criterion from CHA2DS2-VA would lead to less OAC use in female AF patients over the next years remains to be seen.

Aims: This study, using a prospective cohort, evaluated the effectiveness and safety of off-label reduced-dose apixaban vs. the on-label dose in atrial fibrillation (AF) patients meeting a single-dose reduction criterion.

Methods and results: The efficAcy and Safety of aPixaban In REal-world practice in Korean frail patients with AF (ASPIRE) study is a multicentre, prospective observational cohort involving AF patients who met a single-dose reduction criterion of apixaban. Patients were divided into two groups: an on-label standard dose (5 mg twice daily) and an off-label reduced dose (2.5 mg twice daily). The primary effectiveness outcome was stroke/systemic embolism (SSE), and the primary safety outcome was major bleeding. Of 1944 patients (mean age 74.3 ± 7.9 years, 56% women), 997 (51%) were receiving off-label reduced-dose apixaban. The off-label reduced-dose group was older, had more comorbidities, higher concomitant antiplatelet use, and higher CHA2DS2-VASc and HAS-BLED scores. During follow-up (1.0 ± 0.2 year), crude incidence rates were 0.9 vs. 0.7 per 100 person-years for SSE and 0.5 vs. 1.0 for major bleeding in the on-label vs. off-label groups. After inverse probability of treatment weighting, the off-label reduced-dose group showed no significant differences in the risk of SSE [hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.28-1.59, P = 0.370] and major bleeding (HR 1.38, 95% CI 0.44-4.35, P = 0.578) compared with the on-label standard dose group.

Conclusion: In Korean patients with AF meeting a single-dose reduction criterion of apixaban, off-label reduced-dose apixaban showed no significant differences in SSE and major bleeding compared with the on-label standard dose. These findings suggest that individualized anticoagulation strategies, such as reduced-dose apixaban, may be beneficial for patients with a high risk of bleeding.

Aims: Therapeutic advancements have significantly enhanced cancer patient survival rates yet concomitantly increased the prevalence of associated toxicities, such as cancer therapy-related cardiac dysfunction (CTRCD), either symptomatic (heart failure) or not. Using the World Health Organization's VigiBase® individual case safety report database, the aim was to establish the association between anticancer drugs and CTRCD reporting.

Methods and results: This study was a disproportionality analysis conducted in VigiBase® from the initial report of any anticancer drug until 29 February 2024. Reporting odds ratios for CTRCD were evaluated using a stepwise selection procedure and multivariable-adjusted analyses. Subsequently, secondary analyses consisted of the description of CTRCD cases associated with the identified anticancer drugs. ClinicalTrials.gov registration number: NCT06268535. Among 36 580 288 database reports, 42 828 CTRCD cases associated with at least one anticancer drug were identified with death reported in 20.6% of cases (8833 CTRCD cases). Primary analysis revealed 25 anticancer drugs significantly associated with CTRCD reporting, with trastuzumab, doxorubicin, and bortezomib exhibiting the strongest associations. Cancer therapy-related cardiac dysfunction reporting was associated with kinase inhibitors, including BCR-ABL inhibitors, ibrutinib, and osimertinib. New signals were identified for trabectedin, clofarabine, fludarabine, entrectinib, gemtuzumab ozogamicin, and anagrelide. In contrast, immune checkpoint inhibitors and most anti-vascular endothelial growth factor therapies showed no association with CTRCD.

Conclusion: This disproportionality study identified 25 anticancer drugs significantly associated with CTRCD reporting, including new signals. It highlights discrepancies compared with drugs recommended for cardiac dysfunction evaluation in the 2022 ESC Guidelines. This underscores the importance of including CTRCD as a safety endpoint in cancer studies.