European Heart Journal - Cardiovascular Pharmacotherapy最新文献

Aims: Transcatheter mitral valve replacement (TMVR) has become a feasible alternative to surgical mitral valve replacement (SMVR) in selected patients at high surgical risk. The risk of valve thrombosis following SMVR and TMVR, and the optimal antithrombotic therapy following these procedures, remains uncertain. We aimed to compare the incidence of bioprosthetic mitral valve thrombosis (bMVT) after SMVR and TMVR, and the incidence of bMVT between patients on different antithrombotic regimens.

Methods and results: A literature search of Medline, Embase, and Cochrane Library was performed between January 2000 and August 2024. Random-effects models were used to derive pooled estimates of the incidence of bMVT in the absence of prior or active endocarditis and valve thrombosis. A total of 47 studies (6170 patients, total follow-up 9541.8 patient-years) were eligible for inclusion. The overall incidence of bMVT was 5.05 [95% confidence interval (CI) 3.18-8.01, I2 = 82%] per 100-patient-years. Subclinical bMVT was more common than clinically significant bMVT: incidence 19.11 vs. 7.91 per 100-patient-years, adjusted incidence rate ratio (aIRR) 4.62 (95% CI 1.39-15.36), P = 0.012. bMVT was numerically more common after TMVR than SMVR, but the comparison was not statistically significant: incidence 7.03 vs. 0.58 per 100-patient-years, aIRR 2.19 (95% CI 0.72-6.72), P = 0.170. Patients on vitamin-K antagonists (VKA) had a lower incidence of bMVT than patients on direct oral anticoagulants (DOAC; incidence 5.72 vs. 17.08, aIRR 0.31, 95% CI 0.13-0.73, P = 0.007).

Conclusions: bMVT is not uncommon, with numerically higher incidence in transcatheter compared to surgical valves, but the comparison was not statistically significant. VKAs are associated with a lower incidence of bMVT compared to DOACs.

Aims: A genotype-guided P2Y12-inhibitor de-escalation strategy, switching acute coronary syndrome (ACS) patients without a CYP2C19 loss-of-function allele from ticagrelor or prasugrel to clopidogrel, has shown to reduce bleeding risk without affecting the effectivity of therapy by increasing ischaemic risk. We estimated the cost-effectiveness of this personalized approach compared to standard dual antiplatelet therapy (DAPT; aspirin plus ticagrelor/prasugrel) in the Netherlands.

Methods and results: We developed a 1-year decision tree based on results of the FORCE-ACS registry, comparing a cohort of ACS patients who underwent genotyping with a cohort of ACS patients treated with standard DAPT. This was followed by a lifelong Markov model to compare lifetime costs and quality-adjusted life years (QALYs) for a fictional cohort of 1000 patients. The cost-effectiveness analysis was performed from the perspective of the Dutch healthcare system. A genotype-guided de-escalation strategy led to an increase of 57.73 QALYs and saved €808788 compared to standard DAPT based on a lifetime horizon. Probabilistic sensitivity analysis showed that the genotype-guided strategy was cost-saving in 96% and increased QALYs in 87% of simulations. The intervention remained cost-effective in the scenario where prices for all P2Y12 inhibitors were equalized. The genotype-guided strategy remained dominant in various other scenarios and sensitivity analyses.

Conclusion: A genotype-guided de-escalation strategy in patients with ACS was both cost-saving and yielded higher QALYs compared to standard DAPT, highlighting its potential for implementation in clinical practice. Trial registration: ClinicalTrials.gov identifier: NCT03823547.

Background and aims: Amiodarone is frequently prescribed alongside direct oral anticoagulants (DOACs) in atrial fibrillation. There are concerns regarding drug-drug interactions (DDIs) between amiodarone and DOACs. The literature is conflicting on the clinical implications of this DDI, hence we conducted a meta-analysis to compare bleeding risk among patients receiving DOACs, with and without concurrent amiodarone.

Methods and results: A systematic search was conducted for studies published between 1 January 2009 and 26 June 2024 in MEDLINE via PubMed, Embase, and CENTRAL. Included studies compared major bleeding in patients on concurrent amiodarone and DOACs to those on DOACs without amiodarone. Event rates were used to calculate odds ratios (ORs), which were pooled with a random-effects model. Nine studies were identified, which included 124 813 patients on amiodarone/DOACs, and 314 074 on DOACs. The average age was 77.2 years in the amiodarone/DOAC group, compared to 74.4 years in the DOAC group (P = 0.21). Among DOAC patients, there was a statistically significant increase in major bleeding with concurrent amiodarone (OR 1.22, 95% confidence interval (CI) 1.03-1.44, P = 0.02, I2 = 88%). Intracranial bleeding rate was numerically higher in the amiodarone/DOAC group (1.0 vs. 0.4%), but the difference did not reach statistical significance (OR 2.20, 95% CI 0.53-9.06, P = 0.27, I2 = 100%). There were no significant differences in gastrointestinal bleeding (OR 1.10, 95% CI 0.98-1.23, P = 0.12, I2 = 62%) and all-cause mortality (OR 1.38, 95% CI 0.70-2.73, P = 0.35, I2 = 99%).

Conclusion: Concurrent use of amiodarone and DOACs was associated with an increase in major bleeding. This should be considered when co-prescribing these medications.

Despite substantial advances in cardiovascular pharmacotherapy and devices in recent years, prevention and treatment of many cardiovascular diseases (CVDs) remain limited, thus reflecting the need for more effective and safer pharmacological strategies. In this review, we summarize the most relevant studies in cardiovascular pharmacotherapy in 2024, including the approval of first-in-class drugs for the treatment of resistant hypertension and pulmonary arterial hypertension, label expansions for bempedoic acid and semaglutide, and the results of major randomized clinical trials (RCTs) that have met the pre-specified primary endpoints, thereby filling some gaps in knowledge and opening new perspectives in the management of CVD, and those RCTs whose results did not confirm the proposed research hypotheses. We also include a section on drug safety, where we describe the newest data on adverse reactions and drug-drug interactions that may complicate treatment and/or reduce drug adherence with the consequent decrease in drug effectiveness. Finally, we present the most important ongoing phase 2 and phase 3 clinical trials assessing the efficacy and safety of cardiovascular drugs for the prevention and treatment of CVD.

Aims: Cardiologists have only had rare exposure to haemophilia patients and patients with other congenital bleeding disorders during the last decades, as these patients had a reduced life expectancy and were partly protected against thrombosis due to the bleeding disorder. With the availability of effective and safe replacement therapies of clotting factors, the average life expectancy in these populations of patients has significantly increased, and thrombotic complications may occur.

Methods and results: The European Society of Cardiology Working Group on Thrombosis has taken the initiative to broaden the spectrum of these haematological conditions to include patients with a larger variety of congenital bleeding disorders with concomitant cardiac conditions as compared to a recent position paper by the European Haematology Association in collaboration with other societies (ISTH, European Association for Haemophilia and Allied Disorders, and ESO). Management of antithrombotic therapy or thromboprophylaxis in these individuals is challenging due to the wide phenotypes encompassed by congenital bleeding disorders. These include abnormalities in both primary haemostasis (involving von Willebrand factor and platelet function) and secondary haemostasis (related to coagulation factors and fibrinogen). Bleeding disorders range from mild to very severe. Based on existing literature, we provide clinical consensus statements on optimizing antithrombotic treatment strategies for patients with congenital bleeding disorders and highlight the current gaps in knowledge in these complex clinical settings.

Conclusion: Of importance, an individualized approach to antithrombotic therapy is warranted to properly balance the two risks of thrombosis and bleeding. Adoption of the safest interventional techniques, reduction of the intensity and/or duration of antithrombotic therapies, and attention to the safe levels of clotting factors is generally advised.

Background and aims: Multiple anti-inflammatory drugs have been tested for secondary prevention after myocardial infarction (MI), giving mixed results and questioning the efficacy of anti-inflammatory therapy. No head-to-head comparisons between anti-inflammatory drugs have been performed. This study aimed to compare the efficacy and safety of anti-inflammatory drugs for secondary prevention after MI and the relative merits of specific drugs and administration strategies.

Methods and results: Randomized trials of anti-inflammatory therapy for secondary prevention after MI were identified. Primary efficacy and safety endpoints were trial-defined major adverse cardiovascular events (MACEs) and serious adverse events. Secondary endpoints included all-cause death, individual MACE components, serious infection, cancer, and gastrointestinal adverse events. Pairwise meta-analyses were conducted with interaction analyses for drug type and timing of administration, in addition to network meta-analyses. Multiple sensitivity and meta-regression analyses were conducted to explore potential heterogeneity sources. Twenty-eight studies, involving 44 406 patients with a mean follow-up of 11 months, were included. Anti-inflammatory therapy reduced the incidence of MACEs [incidence rate ratio (IRR): 0.92; 95% confidence interval (CI): 0.86-0.98] compared to control, without increasing serious adverse events. However, it was associated with a higher incidence of gastrointestinal adverse events (IRR: 1.21; 95% CI: 1.07-1.36). No significant interaction was observed between the effects of anti-inflammatory therapy on MACE and the timing of administration.

Conclusion: In secondary prevention for MI, anti-inflammatory therapy significantly reduces MACE without increasing serious adverse events, but it is associated with an increased risk of gastrointestinal adverse events.