James S. Kalus

Combination therapy with an ACE inhibitor and an angiotensin receptor blocker for diabetic nephropathy: a meta‐analysis

Aims  Angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) prevent the progression of diabetic nephropathy (DN). Studies suggest that combination renin–angiotensin–aldosterone system (RAAS)‐inhibiting therapy provides additive benefit in DN. However, these studies are small in size. We performed a meta‐analysis of studies investigating combination therapy for DN.

Effect of “Energy Drink” Consumption on Hemodynamic and Electrocardiographic Parameters in Healthy Young Adults

Background: Energy drinks are frequently purported to improve cognitive function and concentration. However, the cardiovascular effects of these drinks have not been adequately studied. Objective: To determine the cardiac effects of a commercially available, multicomponent energy drink in healthy volunteers. Methods: Fifteen healthy adults were Included in this prospective study. Individuals who had chronic medical conditions, ware on chronic medication, or were pregnant or breast-feeding were excluded. Subjects abstained from caffeine for 48 hours prior to and during the study. In the morning on Day 1 of the study, while subjects were in a fasted state, baseline blood pressure (BP), heart rate (HR), and electrocardiographic (ECG) parameters were measured. Participants then consumed 500 mL (2 cans) of an energy drink and measurements were repeated 30 minutes, 1 hour, 2 hours, 3 hours, and 4 hours later. Participants then drank 500 mL of energy drink daily for the next 5 days. Day 1 protocol was repeated on Day 7. Results: On Days 1 and 7, maximum mean systolic BP (SBP), HR, and QTc interval occurred at 4 hours. Maximum diastolic BP (DBP) occurred at 2 hours on Days 1 and 7. Within 4 hours of energy drink consumption, on Days 1 and 7, respectively, SBP increased by 7.9% (p = 0.006) and 9.6% (p < 0.001), HR increased by 7.8% (p = 0.009) and 11.0% (p < 0,001). and QTc interval increased by 2.4% (p = 0.368) and 5.0% (p = 0.052), DBP increased by 7.0% < p = 0.046) and 7.8% (p = 0.063) within 2 hours of energy drink consumption on Days 1 and 7, respectively. Conclusions: Although no significant ECG changes were observed, HR increased 5–7 beats/min and SBP increased 10 mm Hg after energy drink consumption.

Intravenous plus oral amiodarone, atrial septal pacing, or both strategies to prevent post-cardiothoracic surgery atrial fibrillation: The atrial fibrillation suppression trial II (AFIST II)

Background—The effect of a hybrid intravenous and oral prophylactic amiodarone regimen on postcardiothoracic surgery (CTS) atrial fibrillation (AF) is unknown. The impact of active atrial septal pacing on post-CTS AF has not been well characterized. In addition, the effect of using both amiodarone and atrial septal pacing together to prevent atrial fibrillation is unknown. Methods and Results—Patients (n=160) were randomized to amiodarone or placebo and then to pacing or no pacing using a 2×2 factorial design. All therapies began within 6 hours post-CTS. Amiodarone was given by intravenous infusion for the first 24 hours (1050 mg total) followed by oral therapy for 4 postoperative days (4800 mg total). Atrial septal pacing was given for 96 hours. Amiodarone reduced the risk of AF by 43% and the risk of symptomatic AF by 68% (P =0.037 and P =0.019) versus placebo. Atrial septal pacing did not reduce AF or symptomatic AF incidence versus no pacing. The risk of post-CTS AF in the patients receiving amiodarone+pacing was lower than the placebo+no pacing and the placebo+pacing groups (57.9% and 60.5% reductions, P =0.047 and P =0.040, respectively). Conclusions—Amiodarone given as both an intravenous and oral regimen is effective at reducing post-CTS AF but atrial septal pacing is ineffective. Combining amiodarone and pacing is better than placebo with or without pacing but not amiodarone alone.

The Impact of Suppressing the Renin‐Angiotensin System on Atrial Fibrillation

Atrial fibrillation is very common in the United States. After a search of Medline, EMBASE, and CINAHL, 4 trials evaluating inhibitors of the renin‐angiotensin system were identified for prevention of new‐onset atrial fibrillation, facilitation of electrical cardioversion of atrial fibrillation, and prevention of atrial fibrillation recurrence after electrical cardioversion. A meta‐analysis was performed using a random‐effects model. Use of an angiotensin‐converting enzyme (ACE) inhibitor or angiotensin‐receptor blocker (ARB) was associated with a reduction in new‐onset atrial fibrillation (OR [95% CI] = 0.51 [0.36–0.72]), a lower failure rate of electrical cardioversion of atrial fibrillation (0.47 [0.24–0.92]), and a lower rate of recurrence of atrial fibrillation after electrical cardioversion (0.39 [0.20–0.75]). With the exception of the new‐onset atrial fibrillation analysis, these findings were not associated with statistical heterogeneity. These hypothesis‐generating data suggest that inhibitors of the renin‐angiotensin system may provide benefit across the spectrum of atrial fibrillation.

Pharmacologic interventions for reversing the effects of oral anticoagulants

PURPOSE To describe the pharmacologic agents and strategies used for urgent reversal of warfarin and the target-specific oral anticoagulants dabigatran, rivaroxaban, and apixaban. SUMMARY To reverse the anticoagulant effects of warfarin in patients who are bleeding or need surgery, exogenous vitamin K (phytonadione) may be used in combination with another, shorter-acting intervention, such as fresh frozen plasma (FFP), prothrombin complex concentrate (PCC), recombinant factor VIIa, or activated PCC (aPCC). Three-factor PCC contains factors II, IX, and X in an inactivated form, and four-factor PCC also includes factor VII in an inactivated form. No four-factor PCC products are available in the United States, but aPCC, which contains the same four factors with factor VII provided in an activated form, is available. The intervention depends on the International Normalized Ratio, presence of bleeding, and need for and timing of surgery. Research suggests that clotting factor concentrates are more effective than FFP alone for warfarin reversal. These products also may be useful for reversing the effects of target-specific oral anticoagulants, but limited efficacy and safety data are available to support their use. The risks and benefits associated with these products need to be weighed before their use for reversal of dabigatran, rivaroxaban, or apixaban. Additional clinical data are needed to clearly define the role of concentrated clotting factor products in reversal and to determine the optimal clotting factor concentrate product and dose for urgent reversal of oral anticoagulation. CONCLUSION Phytonadione and clotting factor concentrates appear to have a role for reversal of warfarin, and limited evidence suggests that clotting factor concentrates could have a role in reversal of target-specific oral anticoagulants in an emergency situation.

Clinical and safety impact of an inpatient Pharmacist‐Directed anticoagulation service

BACKGROUND Warfarin is implicated in approximately 30% of reported anticoagulant-related errors. In order to improve anticoagulation management and safety, our institution implemented an inpatient Pharmacist-Directed Anticoagulation Service (PDAS). OBJECTIVE To evaluate the impact of this service on both transition of care and safety of patients receiving warfarin anticoagulation. DESIGN Cluster randomized trial. SETTING Large, urban teaching hospital and level 1 trauma center. PATIENTS All patients receiving warfarin on two medical and two cardiology units. INTERVENTION A PDAS provided dosing, monitoring, and coordination of transition from the inpatient-to-outpatient setting. MEASUREMENTS Endpoints were assessed during hospitalization and 30 days after discharge. Transition of care was considered effective if compliance with all of the transition of care metrics occurred. The transition of care metrics included: appropriate enrollment in the anticoagulation clinic, documented inpatient-to-outpatient provider contact, documented inpatient provider-to-anticoagulation clinic communication and patient follow-up with the anticoagulation clinic within five days of discharge. Safety was measured by the composite endpoint of thromboembolism, major bleeding, or international normalized ratio (INR) ≥5. RESULTS This study included 500 patients. Transition of care metric compliance occurred in 73% more patients in the PDAS group (P < 0.001). There was also a 32% reduction in the composite safety endpoint in the PDAS group (P = 0.103). This finding was driven by a reduction in rate of INR ≥5 (P = 0.076). CONCLUSIONS Implementation of a PDAS provides a net improvement in quality of care for the patient taking warfarin in the inpatient setting.

Management of bleeding and reversal strategies for oral anticoagulants: Clinical practice considerations

PURPOSE Currently available clinical data and optimal strategies for reversing oral anticoagulants in patients who are bleeding or need an urgent invasive procedure or operation are reviewed. SUMMARY Bleeding from oral anticoagulants, including new target-specific oral agents (TSOAs), is a common cause of morbidity and mortality, especially in elderly patients. Limited clinical data are available to guide the reversal of warfarin or TSOAs in patients who are bleeding or need an urgent invasive procedure or operation. A panel of five experts with diverse backgrounds in anticoagulation therapy, cardiology, critical care, and emergency medicine and with experience in managing complications of anticoagulation therapy was convened to develop practical strategies for managing patients receiving oral anticoagulants who are bleeding or have an urgent need for an invasive procedure. The strategies were designed to guide clinicians in the acute care setting by providing efficient and potentially effective management concepts to avoid delays in initiating treatment that could adversely affect patient outcomes. The consensus of this expert panel is summarized herein. Recommendations are based on currently available evidence from a comprehensive review of the literature and other pertinent data, along with the experience and expert opinion of the panelists. CONCLUSION Bleeding is a serious complication of the use of oral anticoagulants, and limited information is available to guide the reversal of warfarin or TSOAs in patients who are bleeding or are in need of an urgent invasive procedure. Use of a systematic approach to assessing and treating these patients based on available evidence and expert opinion can help avoid delays that could adversely affect patient outcomes.

Addition of Cilostazol to Aspirin and a Thienopyridine for Prevention of Restenosis After Coronary Artery Stenting: A Meta‐Analysis

The purpose of this study is to evaluate the effect of adding cilostazol to dual antiplatelet therapy (aspirin and thienopyridine) on rates of restenosis after coronary artery stenting. A meta‐analysis is conducted of randomized, controlled trials comparing 3 drug regimens (cilostazol, thienopyridine, aspirin [triple therapy]) with dual antiplatelet therapy to reduce restenosis after coronary stenting. A total of 5 studies are included for analysis. The analysis reveals that triple therapy is used in 796 patients, whereas dual therapy is used in 801 patients. Approximately 56% of patients receive a drug‐eluting stent. The 6‐month restenosis rates are significantly lower with triple versus dual antiplatelet therapy (12.7% vs 21.9%; odds ratio 0.5; 95% confidence interval, 0.38–0.66; P < .001). This benefit is seen regardless of whether a bare‐metal or drug‐eluting stent is used. Rates of major adverse cardiac events and bleeding are reported for 3 of the 5 studies (n = 1426); analysis of these outcomes shows no difference between treatment groups (P = .21 and .48, respectively). The addition of cilostazol to standard dual antiplatelet therapy reduces angiographic restenosis and increases MLD at 6 months without significantly affecting rates of major adverse cardiac events or bleeding.

Effect of diuresis on P-wave duration and dispersion.

Study Objective. To evaluate the effects of changing volume status on P‐wave duration and dispersion in patients with decompensated heart failure.

Response of the ECG to short-term diuresis in patients with heart failure.

Background: Increase in the amplitude of electrocardiogram (ECG) QRS complexes has been observed in patients treated for heart failure (HF), but the underlying mechanism has not been delineated. Also, correlation of augmentation of the QRS potentials with loss of weight has been noted in patients recovering from anasarca of varying etiology, or after hemodialysis. We assessed the effect of diuresis‐based fluid loss in patients treated for HF on the amplitude of ECG QRS complexes.