Dabigatran, a direct thrombin inhibitor, is an oral anticoagulant indicated for the prevention of stroke in patients with atrial fibrillation (AF) and for the treatment and prevention of deep vein thrombosis and pulmonary embolism. Dabigatran, as well as the other new anticoagulants-rivaroxaban, apixaban, and edoxaban-are substrates for P-glycoprotein (P-gp). Although the U.S. labeling for rivaroxaban and apixaban states to avoid concomitant use with phenytoin, a known P-gp inducer, the U.S. labeling for dabigatran and edoxaban are less clear. We describe the first case report, to our knowledge, documenting a drug interaction between phenytoin and dabigatran by using laboratory measurements of dabigatran serum concentrations. A 45-year-old African-American man was admitted to the inpatient cardiology service following defibrillations from his implantable cardioverter defibrillator. The patient was evaluated and received appropriate antitachycardia pacing for atrial tachyarrhythmias for an episode of ventricular tachycardia (VT), and antiarrhythmic therapy with sotalol was initiated to reduce both his AF and VT burden. On review of the patient's medications for potential interactions, it was discovered that the patient was taking both dabigatran and phenytoin. To determine the magnitude of this drug interaction prior to making a change in his anticoagulation regimen, a dabigatran serum concentration was measured. This concentration was undetectable, indicating that phenytoin had a significant influence on dabigatran's metabolism and that this patient was at high risk for stroke. Clinicians should be aware of this interaction between phenytoin and dabigatran as well as with all other new oral anticoagulants. In patients taking phenytoin who require an anticoagulant, only warfarin should be prescribed to minimize the risk of stroke. In addition, the prescribing information for dabigatran should be updated to include other medications that result in a significant reduction in dabigatran serum concentrations, such as phenytoin.

PCSK9 inhibitors are a class of lipid-lowering agents that significantly reduce low-density lipoprotein cholesterol (LDL-C) levels in patients with atherosclerotic cardiovascular disease and hyperlipidemia. Evolocumab is a monoclonal antibody that inhibits PCSK9 and has been evaluated in phase II and III studies as monotherapy, in combination with statins and other lipid-lowering therapies, in patients who are statin intolerant, and in patients with heterozygous and homozygous familial hypercholesterolemia. Data from these studies show that evolocumab significantly reduces LDL-C levels. Treatment with evolocumab also significantly improves levels of other lipid parameters (e.g., apolipoproteins A1 and B, lipoprotein(a), non-high-density lipoprotein cholesterol, and triglycerides). Recent results indicate that LDL-C reduction with evolocumab significantly reduces the risk of cardiovascular events and is also associated with atherosclerotic plaque regression. From a safety standpoint, rates of adverse events (AEs), serious AEs, and AEs leading to discontinuation were similar between evolocumab and controls in clinical trials, and no increase in AEs was observed when evolocumab was used in combination with statins. Patients with elevated LDL-C benefit from evolocumab treatment, suggesting that evolocumab could help meet an unmet medical need in high-risk patient populations with atherosclerotic cardiovascular disease and hyperlipidemia that are unable to reduce LDL-C levels sufficiently with statin therapy alone.

Baseline PR interval does not affect clinical outcomes or reverse remodeling with CRT in mild HF. (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction [REVERSE]; NCT00271154).

Background: Two recent changes in implantable cardioverter defibrillator (ICD) practice are the increased use of single coil leads and less frequent defibrillation threshold (DFT) testing at implantation. Single coil leads have higher mean DFTs which is of unclear clinical significance. Such leads were used in only a minority of subjects in SIMPLE, which showed no benefit of DFT testing. Hypothesis: Clinical characteristics can be used to predict patients at increased risk of an inadequate defibrillation safety margin with single coil leads. Methods: This analysis included 174 consecutive patients undergoing de novo left pectoral, single coil ICD implantation. A standardized modified step down testing algorithm at implantation was used to determine the delivered energy DFT. Logistic regression was used to assess predictors of DFT and of a high DFT (> 25 J). Results: The patient population was 71.3 percent male and 35 percent African American (AA). The mean age was 60.8 ± 14.3 years and ejection fraction was 34.3 ± 15.6 percent. Of twelve clinical factors assessed, the univariate predictors of DFT were age (p < 0.001), male sex (p < 0.001) and AA race (p < 0.001). After covariate adjustment, race, age and ejection fraction were found to be associated with a high DFT. The mean DFT (J) among AA was 16.1 ± 8.8 compared with 13.3 ± 6.5 for the rest of the cohort (p < 0.05). Moreover, 13.1% of AAs had a high DFT compared with 1.7% for the rest of the cohort (p < 0.005). Conclusions: Age, race and sex predict DFTs with single coil leads. AA are at increased risk for a high DFT and thus an inadequate defibrillation safety margin (< 10 J) and should be considered for dual coil leads and/or defibrillation testing at implantation.