American Journal of Cardiovascular Drugs最新文献

Background

Colchicine has been incorporated into major clinical guidelines for the secondary prevention of cardiovascular disease (CVD). However, recent randomized trials have presented contradictory results.

Objective

We aimed to synthesize the current evidence on colchicine in secondary CVD protection, using a cumulative-dose approach.

Methods

We conducted a meta-analysis incorporating all randomized controlled trials (RCTs) globally. RCTs directly comparing colchicine versus placebo/standard care for the secondary prevention of cerebrovascular or coronary vascular disease were included. Odds ratios (OR) were derived for the primary outcome, defined as the prospective occurrence of major adverse cardiovascular events (MACE). Secondary outcomes included mortality, individual components of MACE, C-reactive protein, and adverse effects.

Results

In total, 14 RCTs including 31,397 participants were included. Colchicine significantly reduced MACE (OR 0.80; 95% confidence interval [CI] 0.68–0.94) in both acute atherothrombotic CVD and all CVD (OR 0.72; 95% CI 0.60–0.86) and resulted in significant prospective reductions in C-reactive protein. The threshold effect was apparent, with a protective benefit of colchicine against MACE at higher cumulative exposure ≥ 90 mg-days (OR 0.66; 95% CI 0.52–0.84). Colchicine resulted in no differences in cardiovascular or non-cardiovascular mortality.

Conclusions

Colchicine significantly reduces MACE in both acute atherothrombotic and all CVD across multiple ethnicities, with a threshold protective effect that clinically corresponds to treatment with 0.5 mg daily for at least 6 months. Importantly, there was no signal of increased all-cause mortality.

Registration

PROSPERO identifier no. CRD420251003142.

Despite the well-established benefits of statin therapy in reducing atherosclerotic cardiovascular disease (ASCVD) risk, many patients fail to achieve recommended low-density lipoprotein cholesterol (LDL-C) targets or experience statin intolerance, necessitating alternative approaches. This review examines advances in non-statin lipid-lowering therapies, focusing on proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (monoclonal antibodies and inclisiran), bempedoic acid, and other non-statin lipid medications. We evaluate their mechanisms of action, clinical efficacy, and safety profiles on the basis of landmark trials. A conceptual framework for personalized lipid management is proposed, addressing residual cardiovascular risk, statin intolerance, and complex patient profiles. Clinical decision pathways are presented for high-risk patients, statin-intolerant individuals, and those with adherence challenges. We explore emerging therapies targeting novel pathways, including lipoprotein(a), apolipoprotein C-III inhibitors, angiopoietin-like protein 3 (ANGPTL3) inhibitors, cholesteryl ester transfer protein (CETP) inhibitors, and gene-editing technologies. Implementation barriers, including cost considerations, insurance challenges, and global access disparities, are discussed alongside solutions.

Bruton tyrosine kinase (BTK) plays a pivotal role in B-cell receptor signaling, making it a key therapeutic target in hematologic malignancies. Bruton tyrosine kinase inhibitors (BTKIs) have revolutionized the treatment landscape, improving survival outcomes in conditions such as chronic lymphocytic leukemia and mantle cell lymphoma. However, despite their clinical efficacy, BTKIs—particularly first-generation agents such as ibrutinib—are associated with significant cardiovascular toxicity, including atrial fibrillation, hypertension, bleeding, and, in rare cases, ventricular arrhythmias and heart failure. This narrative review explores the evolving landscape of BTKI-related cardiovascular toxicity, from first-generation drugs to next-generation agents that have improved safety profiles. We summarize current evidence on the incidence, mechanisms, and risk factors of BTKI-induced cardiovascular events and highlight potential predictive tools and mitigation strategies. Given the increasing use of these agents, a comprehensive understanding of their cardiovascular impact is essential for optimizing treatment selection and patient outcomes. Future research should focus on refining risk stratification models and developing cardioprotective strategies to ensure the long-term safety of BTKI therapy.

Cardio-renal-metabolic (CRM) syndrome is an emerging nosological entity that reflects the interaction between metabolic risk factors, chronic kidney disease, and cardiovascular disorders. In recent years, it has attracted particular interest, as it appears to be associated with a growing incidence of cardiovascular events, progression of kidney disease, and mortality. The fact that the syndrome has a complex pathophysiology, multiple risk factors, and deleterious effects on different organs and systems necessitates an interdisciplinary approach to its management. Pharmacological agents with positive effects on different components of CRM syndrome, such as sodium–glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, have recently been added to our pharmacological arsenal. However, these treatments are underprescribed and used at disproportionately low rates given the significant benefits they offer and the strong level of evidence supporting them, highlighting the need for greater vigilance among physicians regarding the recognition and treatment of the syndrome. This article provides recent data on the definition, pathophysiology, staging, and diagnosis of CRM syndrome and the holistic management of affected patients.

Aim

Our aim was to evaluate the safety of empagliflozin in escalating doses among patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis who also have heart failure.

Methods

This single-arm, open-label, dose-escalation study enrolled patients with ESRD on maintenance hemodialysis with heart failure (reduced or preserved ejection fraction) from June to September 2023. Patients sequentially received empagliflozin at doses of 5 mg, 10 mg, and 25 mg daily for 4 weeks per dose, alongside standard care. Pre-dialysis vital signs, electrocardiograms, complete blood counts, and biochemical profiles were monitored weekly. Dose-dependent changes were assessed using linear mixed models.

Results

A total of 17 patients participated, without significant adverse events. Empagliflozin treatment was associated with a significant shortening of QRS duration (regression coefficient − 3.35 ms, P < 0.001), stable QT intervals, increased serum calcium (regression coefficient 0.02 mg/dL, P = 0.004), and decreased bicarbonate levels (regression coefficient − 0.27 mmol/L, P = 0.019). Additionally, diastolic blood pressures measured pre-dialysis significantly increased over time (regression coefficient 1.70 mmHg, P = 0.025).

Conclusion

Empagliflozin at doses of 5 mg, 10 mg, and 25 mg per day, administered sequentially for 4 weeks each, demonstrated a favorable safety profile in patients with ESRD undergoing maintenance hemodialysis. Further studies are warranted to explore clinical implications of the observed physiological changes.

Registration

This was a single-arm, open-label, dose-escalating safety study required by the institutional review board of the National Taiwan University Hospital before the commencement of two randomized controlled trials registered at ClinicalTrials.gov (EMPA-PRED [NCT06249945] and EMPA-RRED [NCT06249932]).

Background

Emerging evidence suggests that sodium–glucose co-transporter-2 (SGLT2) inhibitors reduce cardiovascular events in patients with diabetes mellitus (DM) after acute myocardial infarction (AMI), but evidence in Asian populations remains limited.

Objective

We assessed the impact of SGLT2 inhibitors on in-hospital, 30-day, and 30-day to 1-year mortality in a Northern Chinese real-world cohort.

Methods

An electronic health record-based cohort was constructed from the Tianjin Health and Medical Data Platform from January 2013 to December 2022. Statistical analyses, including Kaplan–Meier survival analysis, multivariable regression analysis, and propensity score matching, were undertaken to evaluate the impact of SGLT2 inhibitors on in-hospital, 30-day, and 1-year mortality rates.

Results

A total of 23,486 patients with both AMI and DM were included. Patients treated with SGLT2 inhibitors (n = 5053) were younger (64.2 vs 67.2 years) and had a higher frequency of dyslipidemia (26.4% vs 18.5%) and history of percutaneous coronary intervention (17.1% vs 15.3%) than those who did not receive them. After multivariable adjustment, the use of SGLT2 inhibitors showed a lower mortality rate during hospitalization (odds ratio 0.44; 95% confidence interval [CI] 0.33–0.58), at 30 days (hazard ratio 0.44; 95% CI 0.36–0.53), and at 30 days to 1 year (hazard ratio 0.86; 95% CI 0.73–1.00). These findings were further supported by propensity score matching and subgroup analyses, which consistently confirmed the reduction in mortality across all three time points.

Conclusion

In a real-world electronic health record-based cohort in China, this study confirmed a mortality benefit with the use of SGLT2 inhibitors in patients with combined DM and AMI. Further studies are needed to validate these benefits across broader populations.

Background

In the CLEAR Outcomes study, 13,970 high cardiovascular risk patients with hypercholesterolemia and statin intolerance were randomized to treatment with bempedoic acid or standard of care (placebo). Bempedoic acid reduced the risk of major adverse cardiovascular events by 13%. However, the cost-effectiveness of bempedoic acid in this patient population is unknown.

Methods

Markov modeling estimated cost-effectiveness of bempedoic acid versus standard of care alone to reduce cardiovascular risk from a US third-party payer perspective. Baseline risk was estimated by applying individual patient characteristics from the trial to established risk equations. Treatment benefit was extrapolated over a lifetime horizon using hazard ratios for individual major adverse cardiovascular event (MACE) components from CLEAR Outcomes. Scenario analyses included on-treatment analysis, alternate bempedoic acid costs, and modeling effects of the fixed-dose combination with ezetimibe on low-density lipoprotein cholesterol (LDL-C) reduction and predicted MACE.

Results

Bempedoic acid was estimated to reduce lifetime MACE (1.58 versus 1.95 per patient) versus standard of care. At list price, bempedoic acid was associated with increased costs (+ $22,600) and improved quality-adjusted life-years (QALYs, + 0.14), resulting in an incremental cost-effectiveness ratio (ICER) of $166,830 per QALY. The on-treatment analysis resulted in an ICER of $70,279 per QALY. Reduction in bempedoic acid price by 25% resulted in lower incremental total costs and an ICER of $99,993 per QALY. Modeling the effects of the fixed-dose combination resulted in an ICER of $40,317 per QALY.

Conclusions

Use of bempedoic acid offers improved lifetime cardiovascular (CV) risk reduction over standard of care in patients with or at high risk for CV disease (CVD) at common cost-effectiveness thresholds ($150,000 per QALY).

Trial Registration

ClinicalTrials.gov identifier: NCT02993406 (CLEAR Outcomes study).