Outcomes of Patients with a Mechanical Heart Valve and Poor Anticoagulation Control on Warfarin.

BACKGROUND: Patients with a mechanical heart valve (MHV) require oral anticoagulation. Poor anticoagulation control is thought to be associated with adverse outcomes, but data are limited. OBJECTIVE: To assess the risks of clinical outcomes in patients with a MHV and poor anticoagulation control on warfarin. METHODS: We conducted a retrospective study of consecutive patients undergoing MHV implantation at a tertiary care center (2010-2019). Primary outcome was a composite of ischemic stroke, systemic embolism, or prosthetic valve thrombosis. Major bleeding and death were key secondary outcomes. We constructed multivariable regression models to assess the association between time in therapeutic range (TTR) on warfarin beyond 90 days after surgery with outcomes. RESULTS: We included 671 patients with a MHV (80.6% in aortic, 14.6% in mitral position; mean age 61 years, 30.3% female). Median follow-up was 4.9 years, mean TTR was 62.5% (14.5% TTR <40%, 24.6% TTR 40-60%, and 61.0% TTR >60%). Overall rates of the primary outcome, major bleeding, and death were 0.73, 1.41, and 1.44 per 100 patient-years. Corresponding rates for patients with TTR <40% were 1.31, 2.77, and 3.22 per 100 patient-years. In adjusted analyses, every 10% decrement in TTR was associated with a 31% increase in hazard for the primary outcome (hazard ratio [HR]: 1.31, 95% confidence interval [CI]: 1.13-1.52), 34% increase in major bleeding (HR: 1.34, 95% CI: 1.17-1.52), and 32% increase in death (HR: 1.32, 95% CI: 1.11-1.57). CONCLUSION: In contemporary patients with a MHV, poor anticoagulation control on warfarin was associated with increased risks of thrombotic events, bleeding, and death.

Incidence and risk factors for acute kidney injury in patients with excessive anticoagulation on warfarin: a retrospective study.

Anticoagulant-related nephropathy is an acute kidney injury (AKI) associated with excessive anticoagulation. The nature of the association between excessive anticoagulation with warfarin and AKI and its incidence remain unclear. To evaluate the incidence of AKI in excessively anticoagulated patients taking warfarin and examine potential risk factors. A retrospective chart review was performed in patients on chronic warfarin. The primary outcome was AKI, defined as an acute increase in creatinine of > 26.5 µmol/L within 7-14 days of an international normalized ratio (INR) ≥ 4.0. 292 patients with an INR ≥ 4.0 were included. 101 patients had CKD and 191 did not have CKD. Of the 292 patients with an INR ≥ 4.0, 38 (13%) had an AKI. In univariable analyses, CKD [odds ratio (OR) 2.1, 95% confidence interval (CI) 0.99-4.43] and use of renin-angiotensin system (RAS) blockers and/or diuretics (OR 3.85; 95% CI 1.15-20.15) were significantly associated with the risk of AKI. In a binomial logistic regression model, use of RAS blockers and/or diuretics was the only significant predictor of AKI (OR 3.4; 95% CI 1.02-11.76). Use of RAS blockers and/or diuretics significantly increased the risk of AKI in patients with warfarin-related excessive anticoagulation. Further prospective studies examining the association of high INRs and AKI are needed.

Postoperative low-molecular-weight heparin bridging is associated with an increase in wound hematoma following surgery for pacemakers and implantable defibrillators.

BACKGROUND: The perioperative management of patients receiving oral anticoagulation therapy (OAC) who undergo pacemaker (PM) and defibrillator (ICD) surgery remains controversial. Low-molecular-weight heparin (LMWH) is often used; however, wound hematoma is a common complication. METHODS: At a single academic Canadian center, between July 2003 and June 2005, details of perioperative OAC bridging and the rate of wound hematoma requiring reoperation or interruption of OAC were reviewed for all patients receiving LMWH bridging for PM or ICD surgery. RESULTS: A total of 148 PM/ICD patients underwent perioperative bridging with LMWH. A significant hematoma occurred in 23 patients, requiring reoperation in three patients. No patient died, developed infection, or stroke. The initial bridging regimen included LMWH (enoxaparin 1 mg/kg BID) given until evening prior to surgery, and reinitiated on postoperative day 3. In response to high rates of postoperative hematoma, subsequent protocols omitted the LMWH on the evening before surgery, all postoperative LMWH, or both. The use of LMWH the night before surgery had no effect on hematoma rates (12% vs 17%, P = 0.62); however, the use of any postoperative LMWH increased hematoma rates (23% vs 8%, P = 0.01). Hematoma rates were not increased in patients receiving acetylsalicylic acid (19% vs 16%, P = 0.62) or clopidogrel (25% vs 17%, P = 0.54). In a multivariate analysis, independent predictors of significant wound hematoma included postoperative LMWH (P = 0.001), a higher international normalized ratio on the day of surgery (P = 0.03), and male sex (P = 0.05). CONCLUSION: Elimination of postoperative LMWH was associated with a substantial reduction in hematoma rates following PM and ICD surgery.

Brief communication: Preoperative anticoagulant activity after bridging low-molecular-weight heparin for temporary interruption of warfarin.

BACKGROUND: Preoperative low-molecular-weight heparin (LMWH) is often used when warfarin therapy is interrupted for surgery. OBJECTIVE: To determine the preoperative anticoagulant activity of LMWH following a standardized "bridging" regimen. DESIGN: Prospective cohort study. SETTING: Single university hospital. PATIENTS: Consecutive patients who had warfarin therapy interrupted before an invasive procedure. INTERVENTION: Enoxaparin, 1 mg/kg of body weight, twice daily. The last dose was administered the evening before surgery. MEASUREMENTS: Blood anti-factor Xa heparin levels measured shortly before surgery. RESULTS: Preoperative anti-Xa heparin levels were obtained in 80 patients at an average of 14 hours after the last dose of enoxaparin was administered. The average anti-Xa heparin level was 0.6 U/mL. The anti-Xa heparin level, measured shortly before surgery, was 0.5 U/mL or greater in 54 (68%) patients and 1.0 U/mL or greater in 13 (16%) patients. A shorter interval since the last dose (P < 0.001) and a higher body mass index (P = 0.001) were associated with higher preoperative anti-Xa heparin levels. LIMITATIONS: The small sample size limits accurate estimates of the frequency of the clinical outcomes. A single regimen of LMWH was evaluated. CONCLUSIONS: Anti-Xa heparin levels often remain high at the time of surgery if a last dose of a twice-daily regimen of LMWH is given the evening before surgery.