Survey of Anticoagulation Practices with the Impella Percutaneous Ventricular Assist Device at High-Volume Centers.

OBJECTIVES: To characterize anticoagulation practices with the Impella percutaneous ventricular assist device (pVAD). BACKGROUND: Managing anticoagulation in patients being supported by the Impella pVAD is made challenging by several unique features of the device. These include the release of a dextrose-based purge solution containing unfractionated heparin (UFH), the need to concurrently administer systemic anticoagulation with intravenous UFH, and the lack of an alternative strategy in patients with contraindications to UFH. METHODS: To characterize anticoagulation practices with the Impella pVAD, we conducted a survey of centers in the United States performing a high volume of Impella cases, which we defined as > 1 per month. Centers were contacted via email or phone and individuals who agreed to participate were provided with a link to complete the survey online. The primary measures of interest were variations in practice across centers and variations from the manufacturer's recommendations. RESULTS: Practices varied considerably among respondents (65 of 182 centers, or 35.7%) and often diverged from manufacturer recommendations. Approximately half of centers (52.4%) reported using a UFH concentration of 50 units/mL in the purge solution, whereas most of the remaining centers (41.3%) reported using lower concentrations. Strategies for the initiation and adjustment of systemic therapy also varied, as did practices for routinely monitoring for hemolysis. Nearly one-fifth of centers (16.7%) had not developed an alternative strategy for the purge solution in patients with contraindications to UFH. Most centers (58.4%) reported using argatroban or bivalirudin in this scenario, a strategy that diverges from the manufacturer's recommendations. CONCLUSIONS: Given these findings, studies to determine a systematic approach to anticoagulation with the Impella device are warranted.

Antithrombotic Usage Patterns in the Era of New Oral Anticoagulant Options for Atrial Fibrillation.

BACKGROUND: Appropriate treatment reduces the risk of stroke in patients with atrial fibrillation (AF). Despite the known benefits of warfarin, anticoagulation prescribing rates remain inadequate in high-risk patients. Over the last 6 years, 4 novel oral anticoagulants have been approved for use for stroke prophylaxis in non-valvular AF (NVAF), which may allow prescribers to tailor therapy for each NVAF patient. OBJECTIVE: The goal of this investigation was to determine the effect of dabigatran and rivaroxaban availability on the rate of anticoagulant prescribing at hospital discharge in patients with a principal diagnosis of NVAF. METHODS: A retrospective chart review of adult patients presenting with NVAF (CHADS2 score ≥2) was conducted using a historical control group of patients from 2009 compared to patients admitted in 2012 following formulary availability of dabigatran and rivaroxaban. In addition to antithrombotic therapy prescribed, subsequent hospitalizations during a 1-year period were reviewed for major bleeding and stroke events. RESULTS: Two hundred patients were enrolled in the study. The rate of anticoagulant prescribing in the 2009 and 2012 groups was 68.3% and 77.1%, respectively (p = .16). Of the patients in the 2012 group prescribed an anticoagulant, 58 (64%) received warfarin, 26 (28%) received dabigatran, and 7 (8%) received rivaroxaban. One patient (1.2%) in the 2009 group and 4 patients (4.4%) in the 2012 group had a major bleed (p = .4). CONCLUSION: There was no statistical difference in the rate of anticoagulant prescribing between the 2 groups. Despite the availability of additional anticoagulant options, the rate of prescribing remains suboptimal in this high-risk population.

Consequences of treating false positive heparin-induced thrombocytopenia.

Identification of patients with heparin-induced thrombocytopenia is encumbered by false positive enzyme-linked immuno assay (ELISA) antibody results, therefore a serotonin release assay (SRA) is used for confirmation. Recently, several studies have demonstrated that increasing the optical density (OD) threshold (currently at 0.4) of the antibody test enhances the positive predictive value. The purpose of this study was to determine the frequency of patients who were ELISA antibody positive but SRA negative, and the costs and bleeding events associated with alternative anticoagulant treatment. We hypothesized that treating patients with a positive ELISA antibody OD value of <1.0 would result in increased cost and bleeding risk. This retrospective chart review was conducted on adult hospitalized patients from 2011 to 2013. Patients with positive ELISA antibodies (OD of 0.4-1.0) and an SRA result were included. Eighty-five patients were identified with positive antibodies (average OD of 0.66), 100 % of which were found to be SRA negative. A total of 59 patients (69 %) received alternative anticoagulants. The average duration of treatment was 3.1 days, and 4 patients (4.7 %) experienced a bleeding event. The cost of testing and laboratory monitoring was $36,346 and the cost of the alternative anticoagulants totaled $47,179. The total cost was $83,525, with an average total cost per patient of $982. This study adds to the body of literature suggesting treatment should only be initiated if the OD is one or greater. The high false positive rate caused increased cost and some bleeding events.

Continuous intravenous antiarrhythmic agents in the intensive care unit: strategies for safe and effective use of amiodarone, lidocaine, and procainamide.

The development of cardiac arrhythmias in the intensive care unit is common and associated with poor prognoses and outcomes. Because of the complexity of patients admitted to the intensive care unit, the management of arrhythmias is often difficult and may require multiple therapeutic interventions. In order for clinicians to appropriately manage arrhythmias, a thorough understanding of all available therapies, including intravenous antiarrhythmic agents, is essential. Suitable antiarrhythmic agents for use in the critical care setting include amiodarone, lidocaine, and procainamide. While these agents can be effective in managing cardiac arrhythmias, they also possess significant disadvantages and require additional monitoring during use. Therapy with these agents is often complicated because of the presence of significant associated adverse effects, clinician unfamiliarity, variable dosing strategies, and the potential for drug-drug interactions. The purpose of this review is to discuss indications and strategies for safe and effective use of amiodarone, lidocaine, and procainamide.

Colchicine for the Treatment of Acute and Recurrent Pericarditis.

OBJECTIVE: To evaluate the literature with colchicine for the acute treatment of pericarditis and prevention of recurrent pericarditis. DATA SOURCES: Searches of MEDLINE (1966-March 2014) and Cochrane Database (1993-March 2014) were conducted using the search terms pericarditis and colchicine. Limits were set for articles written in English with human subjects. Additional data were identified through bibliographic reviews. STUDY SELECTION AND DATA EXTRACTION: Case series and clinical trials identified from the data sources were evaluated. DATA SYNTHESIS: A total of 16 case series and 5 prospective controlled trials were identified in the search. Early observational studies examined the use of colchicine, as an adjunct to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs), in patients with multiple cases of recurrent pericarditis. These studies showed decreased rates of recurrence after the initiation of colchicine therapy and formed the basis of the only available guidelines for the treatment of pericarditis. Since then, 5 randomized controlled trials have been published; 3 trials studied colchicine therapy for 6 months in patients with recurrent pericarditis, and the other 2 studied colchicine therapy for 3 months in patients with acute pericarditis. All 5 trials showed decreased rates of recurrence and symptom persistence, with similar rates of adverse events between study groups. CONCLUSIONS: Clinical controlled trials have shown that colchicine, as an adjunct to aspirin or NSAIDs, is effective in the prevention of recurrent pericarditis and in the management of acute symptoms. Colchicine was generally well tolerated with a low incidence of adverse events.

Comparison of initial warfarin response in obese patients versus non-obese patients.

Achieving therapeutic anticoagulation with warfarin is complicated by substantial inter-patient and intra-patient variability with numerous factors known to influence dose requirements. Obesity is one factor for which there remains no study to date investigating its initial effect on warfarin response assessed by INR, stratified by BMI category in hospitalized patients. To compare initial warfarin response between obese and non-obese patients by evaluating average daily dose (ADD), time required to attain therapeutic INR, and mean discharge dose (MDD), stratified by BMI category. A retrospective review was conducted to evaluate initial warfarin response in hospitalized patients of different BMI categories initiated on warfarin with ≥4 consecutive days of therapy and managed by pharmacy dosing service. 211 patients were included (10 underweight, 45 normal weight, 48 overweight, 71 obese, 37 morbidly obese). Across BMI categories, the percentage of patients attaining therapeutic INR prior to discharge differed (p = 0.0004) with 71.1 % of normal weight therapeutic compared to 42.3 % of obese and 38 % of morbidly obese. Within BMI categories, when comparing ADD between patients therapeutic and subtherapeutic at discharge, no differences were observed, except among overweight patients (5.6 ± 0.3 vs. 7 ± 0.4 mg, p = 0.0143). Compared to normal weight, obese and morbidly obese required a significantly longer median time to achieve therapeutic INR (8 and 10 days vs. 6 days) and a higher ADD (6.6 ± 0.3 and 7.6 ± 0.5 vs. 5 ± 0.3 mg) and MDD (6.7 ± 0.5 and 6.7 ± 0.7 vs. 4.4 ± 0.5 mg). Compared to normal weight, obese and morbidly obese patients had a decreased initial response to warfarin.

Pharmacists: an important resource to improve core measure performance.

In 2001, the Quality Initiative from the Department of Health and Human Services resulted in the development of a set of core measures focused on five patient populations. Although not part of the original list of providers able to document core measures involving medications, pharmacists were added to the list in November 2007. Within the set of core measures, there are 22 of 44 (50%) that are medication related. The authors' purpose is to describe the role of a pharmacist in meeting core measurements and provide an example of how a pharmacist is utilized at our institution.

Analysis of antithrombotic therapy after cardioembolic stroke due to atrial fibrillation or flutter.

BACKGROUND: Guidelines recommend that all patients with atrial fibrillation and a history of ischemic stroke should receive an anticoagulant. Prior analyses show that warfarin is underutilized in most populations. OBJECTIVE: To examine the use of antithrombotic and anticoagulant therapy in patients with atrial fibrillation or flutter during the index hospitalization for acute, ischemic stroke. METHODS: Retrospective electronic medical record review of 200 patients treated at a tertiary care hospital with a primary ICD-9 code for ischemic stroke and a secondary ICD-9 code for atrial fibrillation or flutter. Exclusion criteria were active bleeding, pregnancy, age less than 18, pre-existing warfarin allergy, or dabigatran use. RESULTS: Fifty-two percent of patients received at least one dose of warfarin during the index hospitalization. There was no relationship between CHADS2 score and likelihood of receiving warfarin (P > .05). There was no significant difference in adverse event rate in patients receiving warfarin compared to those receiving aspirin (3.8% vs 9.1%; P = .14), but the rate of hemorrhagic transformation was lower in patients receiving warfarin (1% vs 7%; P = .03). The composite of hemorrhagic stroke or hemorrhagic transformation was significantly lower in patients receiving bridging therapy (0% vs 11%; P = .03). Sixteen patients were readmitted for stroke within 3 months of discharge. Ten were readmitted for ischemic stroke, 3 for hemorrhagic stroke or hemorrhagic transformation, and 3 for systemic bleeding. Ten patients (62.5%) were receiving warfarin at readmission, but only one of these patients had a therapeutic INR. CONCLUSIONS: Warfarin was underutilized as secondary stroke prophylaxis in these high-risk patients. Bridging therapy appeared to be safe and was not associated with an increase in adverse events.

Update on the use of direct oral anticoagulants for the prevention and treatment of thromboembolism.

Following publication of our review article 4 years ago, there has been an uptake in the use of nonvitamin K oral antagonists, also known as direct oral anticoagulants. The most recent Xa inhibitors to receive approval are edoxaban, which has been approved for use in both atrial fibrillation and venous thromboembolism prevention and betrixaban, which has been approved in the USA for extended thromboprophylaxis in the medically ill population. Additional analyses of certain types of atrial fibrillation patients have now become available. Ongoing prescriber vigilance is recommended as additional information continues to emerge with this class of medications. The purpose of this paper is to provide an update on the use of the direct oral anticoagulant agents for the prevention and treatment of thromboembolism.

The effect of obesity on the rate of heparin-induced thrombocytopenia.

: Heparin-induced thrombocytopenia (HIT) occurs in patients receiving heparin-containing products due to the formation of platelet-activating antibodies to heparin and platelet factor 4. Diagnosis includes utilization of a scoring system known as the 4-T score, and HIT laboratory assays. Recently, obesity was identified as a potential factor associated with the development of HIT. The objective of this study was to evaluate the association of HIT with obesity in ICU and general medicine patients. We performed a chart review of adult patients within the Methodist Healthcare System, and included patients who had an ELISA and serotonin release assay laboratory tests reported within same hospital admission in which they also had documented receipt of heparin. Obese patients were compared with nonobese patients (BMI < 30) for the primary outcome of HIT occurrence, and secondary outcomes including rate of thrombosis, 4-T scores, and ELISA optical density values. We also generated a 5-T score by including one additional point for those with a BMI of 30 or more to determine the predictive value of this score in identifying HIT. Obesity was confirmed to be a risk factor for HIT, and the 5-T score model was also predictive of the development of HIT. However, the 5-T score was not statistically more predictive of HIT than the 4-T score. Predicting HIT remains challenging and novel markers of HIT are needed to improve HIT recognition. Although obesity did not improve the 4-T score, it may improve the predictability of other scoring systems, and further investigation is warranted.

ß-Blockade in Heart Failure With Reduced Ejection Fraction: Does Heart Rate Control Influence Readmissions?

BACKGROUND: Raised resting heart rate (HR), >70 beats per minute (bpm), has been shown to be a risk factor for adverse cardiovascular outcomes and hospital readmissions, specifically in patients with heart failure with reduced ejection fraction (HF rEF). Given their mortality benefit, ß-blockers are recommended in HF rEF, with a goal to titrate to a maximum tolerated dose rather than a specific HR target. OBJECTIVE: To determine the impact of optimal HR control achievement prior to hospital discharge on hospital readmissions in patients with HF rEF receiving ß-blockade. METHODS: A retrospective study of patients admitted to 5 adult hospitals within a large urban health-care system, between 2013 and 2015, was conducted. Patients were identified via International Classification of Diseases, Ninth Revision ( ICD-9) coding for acute on chronic HF rEF. RESULTS: Of the 225 patients included, 20% achieved optimal HR control (n = 46, HR <70 bpm; n = 179, HR ≥70 bpm) and only 15% received ß-blocker titration during hospital admission. Of note, 25% of patients receiving ≥50% target dose (n = 79) and 28% receiving 100% target dose (n = 39) achieved optimal HR control. At 30 days, patients with an HR <70 bpm versus HR ≥70 bpm exhibited similar readmission rates (9% vs 11%, respectively; P > .99) and ED visits (11% vs 8%, respectively; P = .57). CONCLUSIONS: Readmission rates were similar among patients with HF rEF despite the majority failing to achieve optimal HR control from ß-blockade. However, ß-blocker dosing remains suboptimal relative to guideline-recommended target doses. Opportunities exist for inpatient clinicians to optimize ß-blockade in an attempt to achieve HR control.

Angioedema Spotlight: A Closer Examination of Sacubitril/Valsartan Safety Results.

Incorporation of neprilysin inhibition into heart failure pharmacotherapy regimens has recently been recommended by U.S. guidelines, based on results from the PARADIGM-HF trial comparing sacubitril/valsartan to enalapril. While most of the discussion has focused on efficacy, a closer examination of the safety results, particularly the incidence of angioedema during the run-in and double-blind periods, is also warranted. Although no major safety concerns were identified, an angioedema risk comparable to enalapril was found, primarily in the black population. Therefore, despite combination with an angiotensin receptor blocker, which historically has a lower incidence of angioedema, the addition of neprilysin inhibition yields an angioedema risk profile comparable to angiotensin converting enzyme (ACE) inhibitors. Clinicians should recognize this safety risk when prescribing sacubitril/valsartan and remain vigilant in counseling patients regarding the signs and symptoms of angioedema. As recommended by the guidelines, avoiding sacubitril/valsartan use concurrently or within 36 hours of the last dose of an ACE inhibitor or in patients with a history of angioedema is also crucial to minimize angioedema risk and prevent patient harm.

Direct oral anticoagulant use in nonvalvular atrial fibrillation with valvular heart disease: a systematic review.

Direct oral anticoagulants (DOACs) are indicated for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF), which, according to the American College of Cardiology/American Heart Association/Heart Rhythm Society atrial fibrillation (AF) guidelines, excludes patients with rheumatic mitral stenosis, a mechanical or bioprosthetic heart valve, or mitral valve repair. However, the data regarding use of DOACs in AF patients with other types of valvular heart disease (VHD) are unclear. We aimed to summarize and evaluate the literature regarding the safety and efficacy of DOAC use in NVAF patients with other types of VHD. After an extensive literature search, a total of 1 prospective controlled trial, 4 subanalyses, and 1 abstract were identified. Efficacy of the DOAC agents in NVAF patients with VHD mirrored the overall trial results. Bleeding risk was significantly increased in VHD patients treated with rivaroxaban, but not for dabigatran or apixaban. Of the bioprosthetic valve patients enrolled in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, no safety or efficacy concerns were identified. In conclusion, subanalyses of DOAC landmark AF trials revealed that dabigatran, rivaroxaban, and apixaban may be safely used in AF patients with certain types of VHD: aortic stenosis, aortic regurgitation, and mitral regurgitation. More evidence is needed before routinely recommending these agents for patients with bioprosthetic valves or mild mitral stenosis. Patients with moderate to severe mitral stenosis or mechanical valves should continue to receive warfarin, as these patients were excluded from all landmark AF trials.

A review on cardiovascular effects of newer hypoglycaemic medications.

Cardiovascular disease (CVD) is the most prevalent cause of morbidity and mortality in diabetic patients. Improvement in cardiovascular complications with glycaemic control and managing cardiovascular risk factors is well established. However, the impact of hypoglycaemic medications on CVD is of increasing importance. In 2008, the U.S. Food and Drug Administration issued study regulations for hypoglycaemic agents after rosiglitazone was shown to increase the incidence of myocardial infarction, and the European Medicines Agency provided their own guidance in 2012. As a result, multiple studies have been published evaluating the cardiovascular safety of newer hypoglycaemic medications. Empagliflozin and liraglutide are among the newer agents that have shown cardiovascular benefit and are now recommended for patients with CVD or are at an increased risk of CVD per the 2017 American Diabetes Association Guidelines. Given the influx of new literature and other ongoing studies, it is important to understand the cardiovascular safety of newer hypoglycaemic medications. The purpose of this article is to provide a comprehensive review of clinical trials conducted evaluating cardiovascular outcomes of newer hypoglycaemic medications and their role within diabetic management. Key Messages With the prevalence of cardiovascular disease in diabetic patients, clinicians should develop a medication regimen that provides both sufficient efficacy for diabetes while also maintaining cardiovascular safety. Of the new diabetic classes, empagliflozin, a sodium-glucose co-transporter 2 inhibitor, and liraglutide, a glucagon-like peptide-1 receptor agonist, have shown cardiovascular benefit in diabetic patients with established cardiovascular disease and are now recommended in current guidelines for this population. Ongoing trials will give more insight to whether cardiovascular benefit is a class effect with sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists and the cardiovascular safety of dipeptidyl peptidase-4 inhibitors.

Peripheral interventions and antiplatelet therapy: Role in current practice.

Peripheral arterial disease (PAD) is a common disorder associated with a high risk of cardiovascular mortality and continues to be under-recognized. The major risk factors for PAD are similar to those for coronary and cerebrovascular disease. Management includes exercise program, pharmacologic therapy and revascularization including endovascular and surgical approach. The optimal revascularization strategy, endovascular or surgical intervention, is often debated due to the paucity of head to head randomized controlled studies. Despite significant advances in endovascular interventions resulting in increased utilization over surgical bypass, significant challenges still remain. Platelet activation and aggregation after percutaneous transluminal angioplasty of atherosclerotic arteries are important risk factors for re-occlusion/restenosis and life-threatening thrombosis following endovascular procedures. Antiplatelet agents are commonly prescribed to reduce the risk of myocardial infarction, stroke and death from cardiovascular causes in patients with PAD. Despite an abundance of data demonstrating efficacy of antiplatelet therapy in coronary artery disease and cerebrovascular disease, there is a paucity of clinical information, clinical guidelines and randomized controlled studies in the PAD population. Hence, data on antiplatelet therapy in coronary interventions is frequently extrapolated to peripheral interventions. The aim of this review article is to elucidate the current data on revascularization and the role and duration of antiplatelet and anticoagulant therapy in re-vascularized lower limb PAD patients.

Pharmacologic Considerations in the Management of Patients Receiving Left Ventricular Percutaneous Mechanical Circulatory Support.

Percutaneous mechanical circulatory support (MCS) devices, including the intraaortic balloon pump, Impella, and TandemHeart, are often used for hemodynamic support in the setting of refractory cardiogenic shock. The thrombotic and bleeding complications associated with these devices is well recognized, and the Impella and TandemHeart devices have unique anticoagulation considerations that may influence patient outcomes. Both devices typically require use of a heparinized purge solution in combination with intravenous unfractionated heparin, thereby providing multiple sources of heparin exposure. Each device also has specific monitoring requirements and goal ranges. This review provides an overview of percutaneous MCS devices commonly used in the acute management of left ventricular failure, with an emphasis on pharmacologic considerations. We review recent evidence and guidelines and provide recommendations for appropriate use of anticoagulation during device support. Approaches to managing heparinized purge solutions, monitoring, and the utility of nonheparin anticoagulants are also provided because high-quality evidence in the literature is limited.

Acute Kidney Injury in Patients Continued on Renin-Angiotensin System Blockers During Hospitalization.

BACKGROUND: Acute kidney injury (AKI) is common in hospitalized patients and is associated with adverse outcomes. This study aimed to evaluate patient characteristics and interventions during hospitalization associated with the development of AKI in patients continued on renin-angiotensin system (RAS) blockers during hospitalization. METHODS: A retrospective study of 184 adult patients admitted between January 2012 and September 2014 and continued on RAS blockers was conducted. Risk factors for AKI were compared between AKI (n = 92) and non-AKI (n = 92) groups. RESULTS: Patients who developed hospital-acquired AKI had a higher baseline serum creatinine (1.2 ± 0.4 versus 1 ± 0.3mg/dL, P < 0.001) and lower estimated glomerular filtration rate (54 ± 10 versus 57 ± 7mL/minute/1.73m2, P = 0.03) compared with patients who did not develop AKI. Patients who developed AKI were also more likely to be admitted to the intensive care unit, have surgical procedures, have hypotension and be prescribed loop diuretics. The presence of chronic kidney disease and hypotension were risk factors associated with AKI development. In addition, the AKI group had a significantly longer length of stay (14 days versus 8 days, P < 0.0001) and had a higher rate of all-cause hospital mortality (9% versus 1%, P = 0.03). CONCLUSIONS: Patients with chronic kidney disease, hypotension and those undergoing surgeries were more likely to develop AKI while receiving RAS blockers. During hospitalization, temporary discontinuation of these medications may be warranted in patients with these characteristics.

Clopidogrel Response Variability: Review of the Literature and Practical Considerations.

Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is standard therapy following acute coronary syndrome and percutaneous coronary intervention. Despite the use of potent antiplatelet agents, vascular events continue to occur. Lack of response to clopidogrel therapy has been widely investigated using various methods of platelet function testing. These studies have consistently found an association between poor clopidogrel response and an increased risk of vascular events. Strategies to overcome this problem include higher clopidogrel doses or the use of an alternative P2Y12 agent. To date, the majority of studies investigating tailored antiplatelet therapy have failed to show any reduction in clinical events likely due to the low-risk population studied. Despite this lack of benefit from altering therapy, platelet function testing may be done in certain patient populations. Patients at high risk of deleterious outcomes from stent thrombosis may be an appropriate patient population for platelet function testing to ensure adequate response to therapy. In addition, emerging data suggests a potential role for platelet function testing to assess for bleeding risk. The purpose of this article is to review the key studies demonstrating response variability to clopidogrel therapy, strategies to overcome variability, and practical considerations for the clinician.

Ivabradine: A Review of Labeled and Off-Label Uses.

Ivabradine is a unique medication recently approved in the USA for the treatment of select heart failure patients. It was first approved for use in several countries around the world over a decade ago as an anti-anginal agent, with subsequent approval for use in heart failure patients. Since ivabradine has selective activity blocking the I f currents in the sinus node, it can reduce heart rate without appreciable effects on blood pressure. Given this heart-rate-specific effect, it has been investigated in many off-label indications as an alternative to traditional heart-rate-reducing medications such as beta blockers and calcium channel blockers. We conducted searches of PubMed and Google Scholar for ivabradine, heart failure, HFrEF, HFpEF, angina, coronary artery disease, inappropriate sinus tachycardia, postural orthostatic hypotension, coronary computed tomography angiography and atrial fibrillation. We reviewed and included studies, case reports, and case series published between 1980 and June 2016 if they provided information relevant to the practicing clinician. In many cases, larger clinical trials are needed to solidify the benefit of ivabradine, although studies indicate benefit in most therapeutic areas explored to date. The purpose of this paper is to review the current labeled and off-label uses of ivabradine, with a focus on clinical trial data.