The FDA recently approved two new oral antibiotics for the treatment of uncomplicated urogenital gonorrhea: zoliflodacin (Nuzolvence®) and gepotidacin (Blujepa®). These approvals represent significant advances in gonorrhea treatment, as resistance to current therapies, including ceftriaxone and azithromycin, continues to increase worldwide. Both drugs offer oral alternatives to injectable ceftriaxone, potentially improving treatment access and patient convenience. The approvals come at a critical time, as the Centers for Disease Control and Prevention declared antimicrobial-resistant Neisseria gonorrhoeae an urgent public health threat in 2019.
In a phase 3, randomized, controlled, open-label, non-inferiority trial (N=930), zoliflodacin demonstrated microbiological cure rates of 90.9% (95% CI 88.1–93.3) compared with 96.2% (95% CI 92.9–98.3) for ceftriaxone plus azithromycin. The treatment difference was 5.3% (95% CI 1.4–8.6), meeting the prespecified non-inferiority margin of less than 12%. The gepotidacin trial (EAGLE-1), a phase 3, randomized, open-label, sponsor-blinded, multicentre, non-inferiority study (N=628), showed microbiological success rates of 92.6% (95% CI 88.0 to 95.8) for gepotidacin versus 91.2% (95% CI 86.4 to 94.7) for ceftriaxone plus azithromycin, with an adjusted treatment difference of -0.1% (95% CI -5.6 to 5.5), also meeting non-inferiority criteria. Both drugs were generally well tolerated, with most adverse events being mild or moderate in severity.
Gepotidacin was recently approved by the FDA for the treatment of uncomplicated urinary tract infections in females, and its gonorrhea indication expands its clinical utility. Zoliflodacin, while FDA-approved, is not yet available in pharmacies as of early 2026. Zoliflodacin is administered as a single 3 g oral dose (mixed with water as an oral suspension), with dosing instructions based on body weight: patients weighing 77 lbs to less than 110 lbs (35 kg to less than 50 kg) should take it on an empty stomach, while those weighing ≥110 lbs (50 kg) should take it with food. Gepotidacin is given as two 3000 mg doses (four 750 mg tablets each) taken approximately 12 hours apart, and should be administered after a meal. Both drugs work on the same bacterial enzymes (DNA gyrase and topoisomerase IV), but they come from different chemical classes: gepotidacin is a triazaacenaphthylene antibacterial, while zoliflodacin is a spiropyrimidinetrione antibacterial. Due to animal studies showing potential fetal harm, zoliflodacin should not be given to pregnant women, and males with female partners of reproductive potential should use effective contraception for at least 3 months after administration. Common side effects of zoliflodacin include neutropenia (7%), headache (10%), leukopenia (4%), dizziness (3%), nausea (3%), and diarrhea (2%). Gepotidacin’s most common adverse reactions include diarrhea (49%), nausea (24%), abdominal pain (15%), vomiting (12%), flatulence (10%), dizziness (8%), soft feces (8%), headache (7%), fatigue (6%), and hyperhidrosis (6%). Both drugs have important drug interactions: zoliflodacin is contraindicated with moderate or strong CYP3A4 inducers, while gepotidacin should not be used with strong CYP3A4 inhibitors and should be avoided with moderate CYP3A4 inhibitors in gonorrhea patients.
Catheter ablation has become a common treatment for atrial fibrillation (AF), and many patients undergo the procedure in hopes of stopping anticoagulation. However, the risks and benefits of discontinuing anticoagulation after successful ablation have not been clearly defined. Current guidelines recommend continuing anticoagulation indefinitely after ablation based on stroke risk factors rather than ablation success, but these recommendations are based on limited evidence from small, nonrandomized studies. Since catheter ablation is not 100% curative and AF can recur without symptoms, stopping anticoagulation after the procedure may increase stroke risk. Conversely, continuing anticoagulation increases bleeding risk. Two recent randomized trials have examined this question.
In the ALONE-AF trial, an open-label, multicenter, randomized clinical trial, 840 patients (mean age 64 years, mean CHA2DS2-VASc score 2.1) with AF who had undergone catheter ablation and had no documented AF recurrence for at least one year were randomized to discontinuing oral anticoagulant therapy (n=417) or continuing it with direct oral anticoagulants (n=423). After two years, the primary outcome, a composite of stroke, systemic embolism, and major bleeding, occurred in 0.3% of the discontinue group versus 2.2% of the continue group (absolute difference, -1.9 percentage points [95% CI, -3.5 to -0.3]; P=0.02). Ischemic stroke occurred in 0.3% and 0.8%, respectively, and major bleeding in 0% and 1.4% (P=0.03). Antiplatelet therapy was used in 8.6% of patients in the discontinue group versus 5.0% in the continue group. In the OCEAN trial, an open-label, randomized, blinded-outcome-assessment trial, 1,284 patients (mean age 66 years, mean CHA2DS2-VASc score 2.2) who had undergone successful catheter ablation for AF at least one year earlier were randomized to rivaroxaban 15 mg daily (n=641) or aspirin 70 to 120 mg daily (n=643) and followed for three years. The primary outcome, a composite of stroke, systemic embolism, or new covert embolic stroke detected by MRI, occurred in 0.8% of the rivaroxaban group versus 1.4% of the aspirin group (relative risk, 0.56; 95% CI, 0.19 to 1.65; P=0.28). Stroke occurred in 0.8% and 1.1%, respectively. Fatal or major bleeding occurred in 1.6% of the rivaroxaban group versus 0.6% of the aspirin group (hazard ratio, 2.51; 95% CI, 0.79 to 7.95).
Both trials demonstrate that stroke rates are very low after successful ablation, with annualized stroke rates of approximately 0.3% to 0.4% in patients without documented AF recurrence. The ALONE-AF trial found that discontinuing anticoagulation was superior to continuing it, primarily due to reduced bleeding events without an increase in stroke risk. The OCEAN trial found no significant difference between rivaroxaban and aspirin for stroke prevention, but rivaroxaban was associated with more bleeding. These findings suggest that for patients with successful ablation and no documented AF recurrence, the stroke risk may be low enough that anticoagulation discontinuation or aspirin therapy may be reasonable alternatives to continued anticoagulation, particularly for patients concerned about bleeding risk. However, both trials emphasize the importance of regular rhythm monitoring to detect AF recurrence, as asymptomatic recurrences can occur. The criteria used in these studies for documenting successful ablation serve as a starting point for selecting patients who may be candidates for anticoagulation discontinuation or de-escalation.
For decades, clinicians have debated the optimal management of asymptomatic high-grade carotid stenosis. While revascularization (stenting or endarterectomy) is often performed to prevent future strokes, previous trials comparing these interventions to medical therapy are outdated, predating the era of high-intensity statins and aggressive blood pressure control. To determine if revascularization provides a benefit over modern pharmacotherapy, researchers conducted CREST-2, a pair of parallel, multicenter, randomized trials involving 2,485 patients with severe asymptomatic carotid stenosis (≥70%).
In the study, all participants received intensive medical management (IMM) involving lifestyle coaching and pharmacotherapy targeting a systolic blood pressure <130 mm Hg and an LDL cholesterol <70 mg/dL. Patients were then randomized into two distinct trials based on their suitability for revascularization type: one comparing carotid artery stenting (CAS) plus IMM versus IMM alone (n=1,245), and another comparing carotid endarterectomy (CEA) plus IMM versus IMM alone (n=1,240). The primary outcome was a composite of perioperative stroke or death (within 44 days) or ipsilateral ischemic stroke up to 4 years. The results were as follows:
The CREST-2 study suggests that the benefit of revascularization for asymptomatic carotid stenosis depends heavily on the modality used. Carotid stenting combined with intensive medical management significantly reduced the risk of stroke or death compared to medical management alone. Conversely, carotid endarterectomy did not demonstrate a statistically significant benefit over medical therapy.
Perhaps the most clinically relevant finding from CREST-2 is the low rate of stroke in the medically managed groups (approximately 1.3% to 1.7% annualized rate). These rates are markedly lower than those seen in historical trials, confirming that modern, aggressive management of blood pressure and lipids is highly effective at stabilizing plaque and preventing events. This poses a challenge to the "fix it" reflex; while stenting offered a relative risk reduction, the absolute risk difference was modest. Furthermore, any procedural intervention carries an upfront risk of periprocedural stroke or death (1.3% to 1.5% in this study).
These findings support a nuanced approach to patient care. For patients with asymptomatic disease who are good candidates for stenting and have a reasonable life expectancy, CAS offers a durable advantage. However, for patients who are surgical candidates or those preferring a conservative approach, intensive medical management alone is a safe and robust strategy, provided that strict targets for blood pressure and lipids are achieved.
