Anticoagulant therapy is the cornerstone of stroke prevention in atrial fibrillation (AF), yet its management in elderly and frail patients remains particularly challenging. This review aims to summarize current evidence, guideline recommendations, and future perspectives regarding the optimal anticoagulant strategy in this vulnerable population. Main findings A narrative review of pivotal randomized clinical trials and major real-world registries was conducted, focusing on outcomes of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in patients aged ≥75 years or meeting frailty criteria. Across studies, DOACs consistently demonstrated similar or superior efficacy compared with VKAs for the prevention of stroke and systemic embolism, with a substantially lower risk of intracranial hemorrhage. Apixaban and edoxaban, particularly at adjusted doses, showed the most favorable balance between thromboembolic protection and bleeding risk. Conversely, switching stable elderly patients from long-term VKAs to DOACs, as in the FRAIL-AF trial, was associated with an early excess of clinically relevant non-major bleeding. Frailty, multimorbidity, renal impairment, and polypharmacy remain critical modifiers of both efficacy and safety, underlining the need for individualized dosing and regular renal function monitoring. Recent European Society of Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS) and the American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guidelines recommend DOACs as the preferred treatment for non-valvular AF, emphasizing comprehensive risk assessment and shared decision-making. Emerging agents, such as factor XI inhibitors, offer a promising approach to minimizing bleeding risk in the elderly, though confirmation of their efficacy against ischemic events remains to be fully established. Conclusions In elderly and frail patients with AF, DOACs represent the first-line anticoagulant therapy when appropriately dosed and monitored. A personalized, multidisciplinary approach incorporating frailty assessment, renal evaluation, and patient preference is essential to optimize outcomes. Future trials specifically enrolling very old and severely frail patients are urgently needed to close existing evidence gaps.

Transcatheter aortic valve replacement (TAVR) is a widely accepted treatment option for patients with severe aortic valve stenosis. However, approximately one-third of patients undergoing TAVR present with a small aortic annulus, which is associated with impaired valve performance. The primary objective of this study was to evaluate 2-year mortality after transfemoral TAVR in patients with a small aortic annulus (valve size ≤23 mm for balloon-expandable valves and ≤26 mm for self-expanding valves), comparing balloon-expandable with self-expanding valves. The CENTER2-study includes data from 25,771 patients undergoing TVR. Patients were propensity score-matched and compared on clinical outcomes. A total of 8,827 (37.2%) patients had a small aortic annulus. Mean age was 81.9 ± 6.3 years, 76.9% were female, and the median STS-PROM score was 4.8% (IQR 2.3 to 5.6). In the matched cohort of 2,692 patient pairs, patients receiving a balloon-expandable valve had higher rates of life-threatening bleeding at 30 days (3.6% vs 2.4%, p = 0.01) and two-year mortality (19.1% vs 15.3%, HR 1.23, 95% confidence intervals 1.07 to 1.43, p = 0.004). However, permanent pacemaker implantation was more frequent in patients receiving a self-expanding valve (21.6% vs 8.7%, p < 0.001). In conclusion, in this large real-world cohort of patients undergoing transfemoral TAVR, more than a third of patients had a small aortic annulus. Patients with a small aortic annulus receiving a balloon-expandable valve had higher 2-year mortality rates. Patients receiving a self-expanding valve had higher rates of permanent pacemaker implantation.

Severely calcified coronary lesions are associated with increased risk of procedural complications, stent underexpansion, and restenosis. While atherectomy prepares vessels for treatment, drug-eluting stents (DES) are traditionally preferred over drug-coated balloons (DCB). DCBs offer a stent-free alternative that may improve vessel remodeling and may require shorter antiplatelet therapy. However, for severely calcified lesions, it remains unclear whether DCB or DES is more effective. Following PRISMA guidelines, a systematic search of PubMed, Embase, Web of Science, Scopus, and Cochrane Central identified randomized controlled trials and adjusted observational studies comparing DCB versus DES following atherectomy. The study endpoints included major adverse cardiovascular events (MACE), all-cause death, myocardial infarction (MI), target lesion revascularization (TLR), and major bleeding. Random-effects models were used to estimate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Eight observational studies comprising a pooled total of 1,968 patients (698 DCB and 1,270 DES) met the inclusion criteria. There was no statistically significant difference between the DCB and DES strategies regarding MACE (RR 1.12; 95% CI 0.85 to 1.47; I[2] = 0%), MI (RR 1.11; 95% CI 0.40 to 3.04; I[2] = 0%), major bleeding (RR 1.11; 95% CI 0.36 to 3.37; I[2] = 0%), all-cause mortality (RR 1.18; 95% CI 0.78 to 1.79; I[2] = 0%), or cardiac death (RR 0.67; 95% CI 0.34 to 1.32; I[2] = 0%). However, DES was associated with a significantly lower risk of TLR in the pooled analysis (RR 1.82; 95% CI 1.14 to 2.91; I[2] = 37.4%) and in the Kaplan-Meier curve (HR = 1.64, 95% Cl 1.11 to 2.42, p = 0.014). In conclusion, following mechanical atherectomy for calcified lesions, both DCB and DES demonstrate favorable MACE, mortality, and safety profiles. However, DES exhibits a consistent association with lower TLR. Given the observational nature and inherent selection biases of the data, these findings cannot establish definitive causal relationships and require caution.

Whether prehospital statin therapy is associated with better outcomes in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) remains unclear. We evaluated the association between priorstatin use and lower 1-year cardiovascular event rates in this population. We analyzed data from 827 consecutive patients with STEMI undergoing primary PCI from a multicenter registry and classified them into a prior statin group (n = 510, 62%) and a nonprior statin group (n = 317, 38%). The primary endpoint was 1-year major adverse cardiovascular events (MACE), defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Inverse probability of treatment weighting (IPTW) was the primary analytic approach. After IPTW adjustment, the prior statin group had a lower weighted 1-year MACE incidence than the nonprior statin group (3.1% vs 7.6%; hazard ratio, 0.31; 95% confidence interval, 0.17 to 0.57). The association between prior statin therapy and lower MACE risk was consistent in multivariable Cox regression and sensitivity analyses using modified IPTW approaches. In conclusion, statin therapy before STEMI onset was associated with lower 1-year cardiovascular event rates after primary PCI, a finding mainly driven by lower mortality.