Faculty Bibliography

A parenteral anticoagulant is indicated in patients with acute coronary syndromes. Which anticoagulant should be preferred in each setting is not clearly established. Bivalirudin administration was considered in acute coronary syndromes after several clinical trials showed decreased bleeding risk with its use compared with the association of unfractionated heparin (UFH) with glycoprotein IIb/IIIa inhibitors (GPIs). Most recent data demonstrate that the bleeding benefit identified in the previous studies was not due to bivalirudin's properties but to higher bleeding incidence in the comparator arm due to the disproportional use of GPIs with heparin. This paper reviews clinical evidence on bivalirudin as anticoagulant in stable angina and acute coronary syndromes.

Endogenous endophthalmitis is a rare condition caused by the hematogenous spread of microorganisms from a remote infection site to the eye. Common predisposing conditions are intravenous drug abuse, diabetes, malignancy, immunosuppression, chronic renal failure, parenteral nutrition or invasive medical procedures. We describe a case of endogenous endophthalmitis in the setting of foot osteomyelitis in a patient with diabetes. A high index of clinical suspicion is required to diagnose this condition early in a patient with diabetes because visual symptoms commonly may be misattributed to retinopathy. Early diagnosis is important.

Bivalirudin and heparin are the major available parenteral anticoagulants for percutaneous coronary intervention (PCI) in ST-segment-elevation myocardial infarction. Even though hard clinical outcomes are comparable with both drugs, bivalirudin appears to be safer (less bleeding events) at the expense of lower short-term efficacy (more acute stent thrombosis events). The selection of anticoagulation during PCI in ST-segment-elevation myocardial infarction should be individualized, taking into account the patient's ischemic and bleeding risk. In patients with increased bleeding risk, bivalirudin might be preferable to heparin, whereas in complex PCI with increased risk for stent thrombosis, heparin is preferable. Further clinical studies are needed to elucidate the role of these drugs in PCI for ST-segment-elevation myocardial infarction in the era of radial approaches, new potent antiplatelet agents and the use of glycoprotein IIb/IIIa inhibitors.

Direct oral anticoagulants have recently emerged as an attractive choice for patients requiring anticoagulation treatment. They have a rapid onset of action and can be administered at fixed doses without the need for routine anticoagulation monitoring. They may present fewer interactions than warfarin but further experience is needed to assess the clinical significance of the interactions with cytochrome CYP3A and P-gp inhibitors/inducers. A higher rate of bleeding has been observed in association with antiplatelet agents or non-steroidal anti-inflammatory drugs. Their safety profile has not been sufficiently studied in the elderly, and in patients with liver disease or severe renal impairment. Dose adjustment is necessary in patients with moderate renal impairment and a higher bleeding rate has been observed in this subgroup, although not higher than with warfarin. The clinical settings that require monitoring of coagulation assays have not yet been specified. Reversal of their anticoagulant effect may be problematic in case of severe bleeding. Therefore, despite the obvious advantages of the direct oral anticoagulants, experience is still lacking for many patient subgroups in which they should be withheld awaiting more data.

Blockade of the renin-angiotensin-aldosterone system (RAAS) is a standard therapeutic intervention in diabetic patients with chronic kidney disease (CKD). Concomitant mineralocorticoid receptor blockade has been studied as a novel approach to further slow down CKD progression. We used PubMed and EMBASE databases to search for relevant literature. We included in our review eight studies in patients of at least 18 years of age, with a diagnosis of type 1 or type 2 diabetes mellitus and diabetic nephropathy, under an angiotensin converting enzyme inhibitor (ACEI) and/or an angiotensin II receptor blocker (ARB) as standard treatment. A subset of patients in each study also received a mineralocorticoid receptor blocker (MRB) (either spironolactone or eplerenone) in addition to standard treatment. Combined treatment with a mineralocorticoid receptor blocker further reduced albuminuria by 23 to 61% compared with standard treatment. Estimated glomerular filtration rate values upon study completion slightly decreased under combined treatment. Blood pressure levels upon study completion were significantly lower with combined treatment in three studies. Hyperkalemia prevalence increased in patients under combined treatment raising dropout rate up to 17%. Therefore, combined treatment by an ACEI/ARB and a MRB may further decrease albuminuria in diabetic nephropathy. This effect may be due to the specific properties of the MRB treatment. Clinicians should regularly check potassium levels because of the increased risk of hyperkalemia. Available evidence should be confirmed by an adequately powered comparative trial of the standard treatment (ACEI or ARB) versus combined treatment by an ACEI/ARB and a MRB.

The last few years have seen many studies, pharmacological molecules, and procedures addressing frequent clinical presentations and scenarios. The multiplicity of therapeutic options for, as examples, anticoagulation, the treatment of anaemia, glycemic control, closure of cardiac defects, nevertheless require validation so that medical practice can be based on clear therapeutic objectives, evidence of its effectiveness, and a certain economic viability. This selective review of the literature summarizes certain studies published this year.

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis is a rare complication of antithyroid drug use that was first described with propylthiouracil. We describe an ANCA-associated rapidly progressive glomerulonephritis in a patient treated with carbimazole during 6 months for Graves disease that resulted in end-stage renal disease. A 66-year-old man treated with carbimazole for Graves disease was admitted for macroscopic hematuria and edema of the lower extremities. Laboratory work-up showed elevated serum creatinine (435 μmol/L), mixed hematuria, nephrotic range proteinuria, and a low positive c-ANCA titer with proteinase-3 specificity. Renal biopsy showed necrotizing, crescentic, pauci-immune glomerulonephritis. Carbimazole was discontinued and hemodialysis was initiated as well as high-dose glucocorticoids and pulses of intravenous cyclophosphamide. Despite immunosuppressive treatment, the patient remained dialysis-dependent at 6 months after diagnosis. Graves disease remained in remission after carbimazole withdrawal. ANCA-associated vasculitis manifesting as glomerulonephritis is a potential adverse effect of all antithyroid drugs. Although prognosis is usually good, end-stage renal disease may ensue in rare cases. Physicians should have a high index of suspicion in patients receiving antithyroid drugs who present with symptoms or signs suggestive of progressive renal disease.

Thromboembolic disorders are among the major causes of morbidity and mortality, and anticoagulation remains the cornerstone of prevention and treatment of these disorders. Although effective, the well-established agents have significant drawbacks. Heparin, low molecular weight heparin, and fondaparinux must be given parenterally, which is inconvenient for long-term or home use. The orally administered vitamin K antagonists (such as warfarin) have a slow onset of action, thus requiring bridging therapy with a parenteral agent when immediate anticoagulation is needed (e.g. inpatients with acute deep vein thrombosis). Because vitamin K antagonists produce a variable anticoagulant response as a result of multiple drug-drug and food-drug interactions and genetic polymorphisms, frequent coagulation monitoring and dose adjustment are required to ensure a therapeutic level of anticoagulation, which is inconvenient for both patients and physicians. In the search for new agents to overcome the drawbacks associated with traditional agents, direct Factor Xa inhibitors (e.g. rivaroxaban, apixaban, and edoxaban) and direct thrombin inhibitors (e.g. dabigatran etexilate) have been developed and are undergoing late-stage clinical evaluation for the prevention and treatment of thromboembolic disorders. These new oral agents have already shown promise in large-scale clinical studies and data suggest that we have entered a new era with novel drugs that are closer than ever to the 'ideal anticoagulant'. Because these new oral agents have a rapid onset of action and can be given at fixed doses without the need for routine coagulation monitoring, they may simplify treatment paradigms and are expected to improve overall clinical outcome.