Michael Militello

Characterization of Post-Operative Risk Associated With Prior Drug-Eluting Stent Use

OBJECTIVES The aim of this study was to assess risk of inpatient surgery at any time after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). BACKGROUND Risk of adverse events, including stent thrombosis (ST), in patients undergoing surgical procedures with prior DES remains poorly defined. METHODS Outcomes of consecutive patients having inpatient surgical procedures after PCI with DES, placed from April 28, 2003 until December 31, 2006 at a tertiary-care medical center, were studied. Primary and secondary end points were 30-day post-operative risk of the Academic Research Consortium (ARC) definite and modified probable definitions of ST and combined 30-day post-operative risk of death, nonfatal myocardial infarction (MI), or ST, respectively. Multivariable logistic regression analyses were used to determine independent risk factors. RESULTS Six hundred six inpatient surgeries on 481 patients with a mean time from PCI to surgery of 1.07 +/- 0.89 years were evaluated. The primary and secondary end points occurred after 11 (2.0%) and 56 (9%) surgeries, respectively. Risk of the combined end point and ST decreased significantly in the first 1 to 6 months after PCI (p < 0.0001 and p < 0.014, respectively); however, risk persisted when time between PCI and surgery was >12 months. Independent correlates of the combined end point include emergency surgery, antecedent MI, the pre-operative use of intravenous heparin, and atherosclerotic lesion length treated with DES. Oral antiplatelet status at time of surgery was not a correlate of events. CONCLUSIONS Risk of 30-day post-operative adverse events, including ST, remains significantly higher when surgery is performed soon after PCI, while intermediate-term risk extending at least 2 to 3 years remains important.

Heparin-induced thrombocytopenia : Treatment options and special considerations

Heparin‐induced thrombocytopenia (HIT) is an immune‐mediated adverse effect that typically manifests several days after the start of heparin therapy, although both rapid‐ and delayed‐onset HIT have been described. Its most serious complication is thrombosis. Although not all patients develop thrombosis, it can be life threatening. The risk of developing HIT is related to many factors, including the type of heparin product administered, route of administration, duration of therapy, patient population, and previous exposure to heparin. The diagnosis of HIT is typically based on clinical presentation, exposure to heparin, and presence of thrombocytopenia with or without thrombosis. Antigen and activation laboratory assays are available to support the diagnosis of HIT. However, because of the limited sensitivity and specificity of these assays, bedside probability scales for HIT were developed. When HIT is suspected, prompt cessation of all heparin therapy is necessary, along with initiation of alternative anticoagulant therapy. Two direct thrombin inhibitors—argatroban and lepirudin—are approved for the management of HIT in the United States, and bivalirudin is approved for use in patients with HIT who are undergoing percutaneous coronary intervention. Other agents, although not approved to manage HIT, have also been used; however, their role in therapy requires further evaluation. A comprehensive HIT management strategy involves the evaluation of numerous factors. Many patients, including those undergoing coronary artery bypass surgery, those with acute coronary syndromes, those with hepatic or renal insufficiency, and children, require special attention. Clinicians must become familiar with the available information on this serious adverse effect and its treatment so that optimum patient management strategies may be formulated.

Argatroban Anticoagulation in Intensive Care Patients: Effects of Heart Failure and Multiple Organ System Failure:

We retrospectively evaluated argatroban dosing patterns, clinical outcomes, and the effects of heart failure and multiple organ system failure on dosing requirements in 65 adult, intensive care patients administered argatroban anticoagulation for clinically suspected heparin-induced thrombocytopenia (n = 56) or history of heparin-induced thrombocytopenia (n = 9). Argatroban was initiated then titrated to achieve target activated partial thromboplastin times 1.5 to 3 times normal control (ie, 42-84 seconds). Overall, argatroban was initiated at 1.14 ± 0.62 µg/kg/min (mean ± SD) and administered for 11.4 ± 9.5 days, with comparable dosing patterns between patients with suspected, versus previous, heparin-induced thrombocytopenia. Sixty-four (98.5%) patients achieved target activated partial thromboplastin times, typically following no or one dose adjustment. Therapeutic doses were lower in patients with, versus without, heart failure (0.58 ± 0.28 vs 0.97 ± 0.6 µg/kg/min, P = .042) and decreased as the number of failed organ systems increased from 1 to 2 to =3 (1.10 ± 0.67 vs 0.87 ± 0.47 vs 0.58 ± 0.47 µg/kg/min, P = .008). From argatroban initiation until patient discharge or death, 11 (16.9%) patients (3 off argatroban) developed thromboembolic complications; 14 (21.5%) died (11 off argatroban, 7 from multiple organ system failure); and 1 (1.5%) required amputation. Nine patients (13.8%) experienced bleeding, none fatal. This experience suggests that argatroban administered at approximately 1 µg/kg/min provides adequate levels of anticoagulation in many intensive care unit patients with suspected or previous heparin-induced thrombocytopenia. Reduced doses are needed when heart failure or multiple organ system failure is present.

Safety of oral dofetilide for rhythm control of atrial fibrillation and atrial flutter.

Background—Although dofetilide is widely used in the United States for rhythm control of atrial fibrillation, there is limited postapproval safety data in the atrial fibrillation population despite its known risk of Torsade de pointes (TdP). Methods and Results—We conducted a retrospective chart review of a cohort of 1404 patients initially loaded on dofetilide for atrial fibrillation suppression at the Cleveland Clinic from 2008 to 2012 to evaluate the incidence and risk factors for in-hospital adverse events and the long-term safety of continued use. Of the 17 patients with TdP during loading (1.2%), 10 had a cardiac arrest requiring resuscitation (1 death), 5 had syncope/presyncope, and 2 were asymptomatic. Dofetilide loading was stopped for 105 patients (7.5%) because of QTc prolongation or TdP. Variables correlated with TdP were (1) female sex, 2) 500-&mgr;g dose, (3) reduced ejection fraction, and (4) increase in QTc from baseline. One-year all-cause mortality was higher in patients who continued dofetilide compared with those who discontinued use (hazard ratio, 2.48; 95% confidence interval, 1.08–5.71; P=0.03). Those patients who had a TdP event had higher one-year all-cause mortality than those who did not (17.6% versus 3% at 1 year; P<0.001). Conclusions—Dofetilide loading has a low but finite risk of TdP and other adverse events that warrant the current Food and Drug Administration–mandated practice of inpatient monitoring during drug loading. In this cohort, all-cause mortality was higher at 1 year in those patients continued on dofetilide and in those patients who experienced TdP while loading.

Safety of “Bridging” With Eptifibatide for Patients With Coronary Stents Before Cardiac and Non-Cardiac Surgery

Patients with previously implanted coronary stents are at risk for stent thrombosis if dual-antiplatelet therapy is prematurely discontinued. Bridging with a glycoprotein IIb/IIIa inhibitor has been advocated as an alternative, with few supporting data. The aim of this study was to determine the safety of such a strategy by retrospectively analyzing bleeding in 100 consecutive patients with previously implanted coronary stents who were bridged to surgery with eptifibatide after discontinuing thienopyridine therapy. A propensity-matched control comparison was performed for a subgroup of 71 patients who underwent cardiovascular surgery. Blood transfusions were required in 65% in the bridged group versus 66% in the control group (p = 0.86). The mean numbers of units transfused were 4.84 ± 6.93 and 3.65 ± 7.46, respectively (p >0.25). Rates of return to the operating room for bleeding or tamponade were 10% and 2.9%, respectively (p = 0.085). Increased rates of transfusion were noted for patients who received concomitant aspirin and/or intravenous heparin infusion. In conclusion, there does not appear to be any increase in the need for blood transfusions or rate of return to the operating room for patients being bridged with eptifibatide when thienopyridines are discontinued in the perioperative period, but concomitant use of additional antiplatelet or anticoagulant agents may increase transfusions and delays to surgery. Clinicians who are considering this strategy must weigh the risks of stent thrombosis versus bleeding.

Low-Dose 3-Factor Prothrombin Complex Concentrate for Warfarin Reversal Prior to Heart Transplant

Background: Anticoagulation with warfarin is common in patients presenting for heart transplant. Prior to surgery, anticoagulation reversal is necessary to avoid significant intraoperative and perioperative bleeding complications. Commonly, warfarin reversal is achieved with vitamin K and fresh frozen plasma (FFP); however, these therapies have significant limitations. An alternative to FFP for reversal exists with prothrombin complex concentrate (PCC). A warfarin reversal protocol prior to heart transplant was implemented using low-dose PCC at our institution. Objective: To assess blood product use, effectiveness, and safety post–low-dose PCC administration in patients needing warfarin reversal prior to heart transplant compared with historical controls. Methods: This was a single-center, retrospective cohort study. The PCC cohort included patients undergoing heart transplant presenting with an international normalized ratio ≥1.5 on warfarin therapy and who received at least 1 dose of PCC. Blood product use was measured from postoperative day 0 to 2. Results: The PCC and historical control cohorts included 16 and 50 patients, respectively. There was a significant reduction in the use of FFP (4 vs 8 units, P = 0.0239) in the PCC cohort compared with the historical control cohort. No differences were identified in the use of other blood products as well as other secondary efficacy or safety end points. Conclusions: Use of PCC, per the reversal protocol, prior to heart transplant reduced FFP use and showed a non–statistically significant trend toward reductions in the use of other blood products in the intraoperative and perioperative setting, with no difference identified in thrombotic or embolic complications compared with historical controls.

Alteplase for central catheter clearance: 1 mg/mL versus 2 mg/2 mL

TO THE EDITOR: Tissue plasminogen activator (alteplase) has emerged as the agent of choice for catheter clearance.1 The most commonly studied and used dose is 2 mg/2 mL,1-4 yet such a dose may exceed the actual volume of the catheter, wasting potentially half of the dose. Since the priming volume of many central venous catheters is approximately 1 mL, and because the standard concentration of alteplase is 1 mg/mL, we hypothesize that using alteplase 1 mg/mL is as effective as 2 mg/2 mL for catheter clearance. This report describes the study we performed to establish the clinical equivalence of alteplase 1 mg/mL versus 2 mg/2 mL for catheter clearance. Methods. This randomized, unblinded trial enrolled adults with catheter occlusions. Single-, double-, or triple-lumen tunneled catheters or implanted ports were included. Occlusions were defined as the inability to infuse into or withdraw from the catheter. Patients were randomized to receive alteplase 1 mg/mL or 2 mg/2 mL (Figure 1). The doses were aliquoted from 50-mg vials of alteplase and frozen until time of use.1 In the event a patient had >1 occluded lumen, the same dose was administered to each occluded lumen. Data were analyzed using Blackwelder’s method.5 We considered doses to be equivalent if the clearance rates were within 10% of each other. Treatments were considered equivalent if the 95% CI of the difference in lumen clearance rates between treatment groups was between –10% and 10%. With an α level of 0.05, 226 lumens were needed to ensure 80% statistical power to demonstrate equivalence according to our a priori criteria. Results. Patients were enrolled between May 2001 and May 2002; however, due to lower than expected subject accrual, the study was stopped before the target 226 lumens were enrolled. A total of 61 lumens in 45 patients were enrolled. One-third of the lumens were implanted ports and the other two-thirds were tunneled catheters. All catheters fit the criteria due to the inability to withdraw, whereas 43% of the lumens had dysfunction described as both inability to infuse and withdraw. Thirty-seven lumens were randomized to receive alteplase 1 mg/mL. Clearance rates after one dose of alteplase 1 mg/mL versus 2 mg/2 mL were 81.1% and 83.3%, respectively (% difference –2.3%; 95% CI –18.7% to 14.1%). Similarly, clearance rates after 1 or 2 doses were 85.5% for alteplase 1 mg/mL and 87.5% for alteplase 2 mg/2 mL (% difference –1.0%; 95% CI –15.5% to 13.4%). No adverse events were reported in either group during the study. Numerous studies have examined the use of alteplase for catheter clearance. Our study offers advantages over previous literature in that it was a randomized trial examining 2 doses of alteplase in central venous catheters. Although the statistical criteria for equivalence were not reached, the clearance rates for the different doses of alteplase were similar. Therefore, since the 2 mg/2 mL dose is greater than the priming volume of the catheter, it appears reasonable to use alteplase 1 mg/mL as an initial dose for clearing central venous catheter occlusions.

Teaching an Old Dog New Tricks: Colchicine in Cardiovascular Medicine

Colchicine is one of the oldest known drugs that remains part of the current pharmacopeia. Recent studies have examined the efficacy of colchicine in cardiology with promising results. We conducted a search of electronic databases for studies on colchicine in cardiovascular medicine published through October 2016. As the utilization of colchicine in the management of cardiac conditions grows, it is paramount that internists and cardiologists are familiarized with its benefits and risks. We present a comprehensive review of the role of colchicine in the management of cardiovascular diseases with a strong emphasis on side effects and potential drug interactions.

SAFETY OF ORAL DOFETILIDE LOADING FOR RHYTHM CONTROL OF ATRIAL ARRHYTHMIAS

Although dofetilide is widely used in the United States for rhythm control in patients with symptomatic atrial fibrillation (AF), there is minimal safety data in the AF population despite its known risk of Torsade de pointes (TdP). We conducted a retrospective chart review of a cohort of 1,404

Sedation in the coronary intensive care unit: An adapted algorithm for critically ill cardiovascular patient

In the current era, cardiovascular intensive care units care for more complex patients who are far sicker than historical post-myocardial infarction patients, and sedation has become a common intervention in these units. Current sedation best practices derive mainly from non-cardiac units which limits their generalization to the critically ill cardiac patient. Thus, a great variability in sedation protocols, especially the selection of sedative agents, is commonly seen in daily practice across cardiac units. We present an updated review on sedation in cardiovascular critical care medicine with emphasis on the hemodynamic impact. The goal of this review is to generate a general sedation algorithm specific for the cardiac patient.