The factor XI-directed antisense oligonucleotide IONIS-416858 was compared with enoxaparin in 300 patients undergoing elective knee arthroplasty. Patients were randomized to receive IONIS-416858 at doses of 200 or 300 mg starting 35 days prior to surgery, or enoxaparin at a dose of 40 mg starting after the surgery. The 200 mg IONIS-416858 regimen was noninferior and the 300 mg IONIS-416858 regimen was superior compared with enoxaparin in preventing the composite end point of asymptomatic DVT, symptomatic DVT or pulmonary embolism, or VTE- The rates of major or clinically relevant nonmajor bleeding were 3% in both IONIS- 416858 groups and 8% in the enoxaparin group. With respect to patients with AF, potential unmet needs addressed by these agents include patients at high risk for bleeding, such as those with end-stage renal disease who are on hemodialysis (ongoing phase 2 study).141 Another area of interest is in patients with mechanical heart valves. Data from a phase 2 trial of dabigatran in patients with mechanical heart valves (Randomized, Phase II Study to Evaluate the Safety and Pharmacokinetics of Oral Dabigatran Etexilate in Patients after Heart Valve Replacement [RE-ALIGN]) demonstrated inferior ef cacy and more bleeding, compared with warfarin.142 Factor XI-directed strategies may be very effective in this setting because factor XI depletion abolished mechanical valve- induced thrombin generation in vitro.140 Recommendations 6. For patients with AF, we recommend against antiplatelet therapy alone (monotherapy or aspirin in combination with clopidogrel) for stroke prevention alone, regardless of stroke risk (Strong recommendation, moderate quality evidence). Remark: Patients with AF might have other indications for antiplatelet drugs (eg, acute coronary syndrome, stents). 7. In patients with AF who are eligible for OAC, we recommend NOACs over VKA (Strong recommendation, moderate quality evidence). 