European Heart Journal - Cardiovascular Pharmacotherapy最新文献

Cardiovascular adverse effects of drugs has significant practical implications for patient management. While cardiovascular adverse effects have commonly been associated with oncologic therapeutics, a growing body of evidence suggests that non-oncologic medications can also be associated with significant cardiovascular harm. These adverse effects range from arrhythmias, conduction abnormalities, QT prolongation, heart failure, myocardial infarction, or structural cardiomyopathy. Non-oncologic drugs that have been implicated include antibiotics (e.g., macrolides, fluoroquinolones), antidiabetics (e.g., thiazolidinediones), non-steroidal anti-inflammatory drugs (NSAIDs), drugs for gastrointestinal and urological conditions, and most importantly, cardiovascular drugs. In this narrative review, we focus on the most common non-oncologic drugs that cause cardiovascular adverse effects, their proposed underlying mechanisms with particular emphasis on their clinical manifestations and clinical implications for everyday cardiovascular practice.

Aims: To analyse utilization and discontinuation of secondary preventive medications after acute myocardial infarction (MI).

Methods and results: In separate analyses for each drug [statins, beta-blockers, aspirin, and renin-angiotensin-aldosterone system (RAAS) inhibitors], patients with a first-time MI (2006-2021) registered in the nationwide Swedish MI register SWEDEHEART, surviving >30 days, and discharged with a new prescription of the drug were included. Based on filled prescriptions, treatment initiation, discontinuation (defined as ≥90-day period of non-treatment after the end of previous prescriptions), reinitiation (restarting treatment after discontinuation), and the proportion of patients with ongoing treatment at various time points after the MI were assessed. The analyses included 159 155 patients: 122 288 patients discharged with a statin, 79 968 with a RAAS inhibitor, 105 095 with a beta-blocker, and 127 463 with aspirin: 95%-97% of the patients filled their first prescription for the drug. Treatment discontinuation ranged from 12% to 14% at 1 year, 27%-37% at 5 years, and 36%-51% at 12 years across drugs. Among those who discontinued treatment, the proportion who reinitiated treatment was 28%-46% at 1 year, 42%-62% at 5 years, and 47%-67% at 12 years after discontinuation across drugs. The proportion of patients who were alive with ongoing treatment (regardless of previous discontinuation/reinitiation episodes) was 91%-92% at 1 year, 79%-82% at 5 years, and 74%-79% at 12 years after the index MI.

Conclusion: Discontinuation of secondary preventive medications was common, but so was reinitiation. Thus, the proportion of patients with ongoing treatment was 91%-92% at 1 year and 74%-79% at 12 years after the MI. This study, which did not assess reasons for drug discontinuation, indicates that long-term utilization of secondary preventive medication after MI may not be as low as previously thought.

Aims: This network meta-analysis of randomized controlled trials (RCTs) evaluates the comparative safety and efficacy of intra-coronary (IC) pharmacological and procedural treatments-on top of balloon angioplasty and stent placement-on clinical outcomes and surrogate endpoints of coronary microvascular obstruction (CMVO) in patients with ST-elevation myocardial infarction (STEMI).

Methods and results: Two electronic databases were searched for eligible studies. Primary efficacy endpoints included all-cause mortality, non-fatal myocardial infarction (MI), and heart failure (HF) hospitalization. Primary safety endpoints included peri-procedural arrhythmias including atrioventricular blocks (AVBs) and ventricular fibrillation/sustained ventricular tachycardia (VF/SVT), any bleeding, and stroke. Secondary efficacy endpoints included the occurrence of post-procedural thrombolysis in myocardial infarction (TIMI) flow grade 0-2 and ST-segment resolution. A total of 64 RCTs involving 27 243 patients were included. In mixed comparisons, no treatment significantly reduced the incidence of primary efficacy endpoints compared to conventional primary PCI during a mean follow-up of 8 months. Several treatments significantly reduced the occurrence of post-PCI TIMI 0-2 flow grade [adenosine: 0.40 (odds ratio), (95% Confidence Interval 0.24-0.68); verapamil: 0.22 (0.07-0.69); tirofiban: 0.43 (0.27-0.71); manual thrombus aspiration (TA): 0.61 (0.45-0.82); fibrinolytic + manual TA: 0.24 (0.12-0.48); tirofiban + manual TA: 0.32 (0.14-0.75)], compared to conventional primary PCI. IC administration of tirofiban increased the risk of any bleeding [incidence rate ratio: 1.65 (1.11-2.45)], while IC adenosine increased the risk of peri-procedural AVBs [OR: 2.80 (1.14-6.84)]. Nicorandil reduced the incidence of peri-procedural VF/SVT [OR: 0.31 (0.12-0.81)].

Conclusion: Adjunctive IC treatments during primary PCI do not influence hard clinical outcomes compared to conventional therapy within a mean 8-month follow-up, although several of them lead to an improvement in surrogate endpoints of CMVO.

Study registration number: CRD42023468559.

Aims: The optimal short-term antithrombotic strategy following left atrial appendage occlusion (LAAO) remains uncertain, with the need to balance thromboembolic prevention and bleeding risk presenting a critical challenge. Recent evidence suggests that direct oral anticoagulants (DOACs) may provide a favourable safety-efficacy profile, with low-dose regimens showing potential benefits during the device endothelialization period. This network meta-analysis (NMA) aimed to compare the efficacy and safety of various antithrombotic strategies, including DOAC dosing, following LAAO.

Methods and results: A systematic review and NMA were conducted following Cochrane and PRISMA guidelines. Eligible studies included randomized controlled trials (RCT) and observational studies comparing at least two antithrombotic regimens in patients with non-valvular atrial fibrillation undergoing percutaneous LAAO. Primary outcomes were major bleeding and thromboembolism. Secondary outcomes included device-related thrombosis (DRT) and all-cause mortality. Pairwise and network meta-analyses were performed using a random-effects model. A total of 52 studies (49 observational and 3 RCTs) involving 69 751 patients were included. DOACs were consistently associated with significantly lower rates of major bleeding and all-cause mortality than other antithrombotic regimens. Low-dose DOACs showed a potential advantage over standard-dose DOACs in reducing major bleeding risk (odds ratio 0.45, 95% confidence interval: 0.22-0.92). For thromboembolism and DRT, standard-dose DOAC significantly reduced risk compared with single antiplatelet therapy (SAPT) but not with dual antiplatelet therapy (DAPT), whereas low-dose DOAC significantly reduced both outcomes compared with SAPT, DAPT, and vitamin K antagonists plus SAPT. In ranking analysis, DOACs emerged as the most effective and safest antithrombotic strategy, with low-dose DOACs demonstrating further safety benefits in bleeding outcomes.

Conclusion: DOACs provide a superior safety-efficacy profile compared with other antithrombotic strategies following LAAO, significantly reducing the risks of major bleeding, thromboembolic events, and mortality. While low-dose DOACs may offer additional bleeding risk reduction without compromising efficacy, further research is warranted to confirm their role in clinical practice.