Steven Baroletti

Medication Adherence in Cardiovascular Disease

A 66-year-old woman presents to the emergency department with crushing chest pain and ST-segment elevations on ECG. She has left ventricular systolic dysfunction (ejection fraction, 35%) after recent (6 days earlier) non–ST-segment elevation myocardial infarction treated with percutaneous coronary intervention, including 2 drug-eluting stents. She is sent for emergent cardiac catheterization, is found to have in-stent thrombosis, and subsequently is revascularized. After being transferred to the coronary care unit, she undergoes further workup. Before her previous admission, her home medication regimen included aspirin, lisinopril, atenolol, atorvastatin, spironolactone, furosemide, potassium, and sublingual nitroglycerin. At the time of her latest discharge, her medication regimen consisted of an increased dose of aspirin, the addition of clopidogrel, and a change in atenolol dose, in addition to all other previous medications. During the history and physical examination, it is discovered that she had not filled any of her new prescriptions after discharge from the hospital 5 days ago. She explains, “I already had all my drugs in my medicine cabinet at home.” Nonadherence to medications has been documented to occur in >60% of cardiovascular patients.1 Self-reported adherence to cardiovascular medications in patients who have coronary artery disease is <40% for the combination of aspirin, β-blocker, and a lipid-lowering agent in both isolated and long-term follow-up surveys2 (Table 1). View this table: Table 1. Adherence Rates to Common Cardiovascular Medications The immediate discharge period is a time of high risk for nonadherence. Nearly 1 in 4 patients is partially or completely nonadherent in filling prescriptions after discharge.3 Of the patients who are initially adherent, up to 50% will discontinue antihypertensive medications within …

Everolimus: A Proliferation Signal Inhibitor with Clinical Applications in Organ Transplantation, Oncology, and Cardiology

Everolimus, a proliferation signal inhibitor in the mammalian target of rapamycin (mTOR) drug class, has many clinical applications, including in organ transplantation, oncology, and cardiology. It currently has United States Food and Drug Administration (FDA) approval for prophylaxis against rejection in de novo renal transplant recipients, treatment of renal cell carcinoma, and use as a drug‐eluting stent. To review the pharmacology, pharmacokinetics, efficacy, and safety of everolimus, we performed a search of the MEDLINE database (January 1997–April 2010) for all English‐language articles of in vitro and in vivo studies that evaluated everolimus, as well as abstracts from recent scientific meetings and the manufacturer. In transplantation, everolimus demonstrates immunosuppressive properties and has been used to prevent acute rejection in cardiac, liver, lung, and renal transplant recipients. It appears that this agent may be potent enough to allow for the minimization or removal of calcineurin inhibitors in the long‐term management of renal transplant recipients. In oncology, everolimus has been proven effective for the management of treatment‐resistant renal cell carcinoma. In cardiology, everolimus is available as a drug‐coated stent and is used in percutaneous coronary interventions for prevention of restenosis. In transplant recipients and patients with renal cell carcinoma, everolimus appears to have an extensive adverse‐event profile. The pharmacologic properties of everolimus differentiate this agent from other drugs used in these clinical areas, and its pharmacokinetic properties differentiate it from sirolimus.

Efficacy and Safety of Low‐Dose Valganciclovir for Prevention of Cytomegalovirus Disease in Renal Transplant Recipients: A Single‐Center, Retrospective Analysis

Study Objective. To evaluate the safety and efficacy of valganciclovir 450 mg/day for 6 months for cytomegalovirus (CMV) prophylaxis in renal transplant recipients.

Thrombosis in Suspected Heparin-induced Thrombocytopenia Occurs More Often with High Antibody Levels

OBJECTIVE The study objective was to determine whether higher antiplatelet factor 4 (PF4)/heparin antibody levels using an enzyme-linked immunosorbent assay are associated with more frequent thrombotic events in patients with clinically suspected heparin-induced thrombocytopenia. Heparin-induced thrombocytopenia is an immune-mediated adverse drug reaction. An enzyme-linked immunosorbent assay detects anti-PF4/heparin antibodies to support a suspected clinical diagnosis of heparin-induced thrombocytopenia. The utility of quantitative enzyme-linked immunosorbent assay results is uncertain. METHODS Our single-centered study evaluated quantitative anti-PF4/heparin antibody levels using an enzyme-linked immunosorbent assay in consecutive hospitalized patients with a clinical suspicion of heparin-induced thrombocytopenia and positive anti-PF4/heparin antibody levels between July 2003 and December 2006. RESULTS Overall, anti-PF4/heparin antibody values were available for 318 patients with clinically suspected heparin-induced thrombocytopenia. The median level was 0.85 optical density units (range 0.31-4.0). The overall rate of arterial or venous thrombosis was 23.3%. A 1-unit increase in anti-PF4/heparin antibody level was associated with an approximate doubling in the odds of thrombosis by 30 days (odds ratio, 1.9; 95% confidence interval, 1.5-2.6; P=.0001). The proportion of patients with pulmonary embolism increased with higher anti-PF4/heparin antibody levels. CONCLUSION Higher levels of anti-PF4/heparin antibody are associated with increased thrombosis risk among patients with clinically suspected heparin-induced thrombocytopenia and might have clinical utility for prediction of true heparin-induced thrombocytopenia and the development of thrombosis.

Multi-screen electronic alerts to augment venous thromboembolism prophylaxis

Venous thromboembolism (VTE) prophylaxis in high-risk patients is frequently underutilised. We previously devised a one-screen computer alert program that identified hospitalised patients at high risk for VTE who were not receiving prophylaxis and advised their physicians to prescribe prophylaxis. While this strategy reduced the 90-day incidence of symptomatic VTE by 41%, the majority of electronic alerts were ignored. We have now developed a serial three-screen alert computer program designed to educate physicians who initially declined to order prophylaxis after a single screen alert. Of a total cohort of 880, the responsible physicians for 425 patients received a single electronic alert, whereas 455 who declined prophylaxis after the first screen received the second and third screens of the novel three-screen alert. Our enhanced serial three-screen alert program generated VTE prophylaxis orders for 58.4% of the 455 patients whose physicians initially declined to order prophylaxis following the one-screen alert. There was no significant difference in symptomatic 90-day VTE rates between the two cohorts (2.8% for the one-screen vs. 2.2% for the three-screen, p=0.55). We conclude that our three-screen computer alert program can markedly increase prophylaxis among physicians who decline an initial single screen alert.

Heparin-induced thrombocytopenia (HIT): clinical and economic outcomes.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug reaction that occurs following exposure to unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). HIT with thrombosis (HITT) can cause devastating venous thromboembolism or arterial clots, prolonged hospitalization, and increased costs. To explore the economic and clinical implications of HIT and HITT, we initiated a single-center patient registry. In this report, we describe patient characteristics, comorbidities, management strategies, clinical outcomes, and costs. We enrolled 349 hospitalized patients with an enzyme immunoassay-confirmed diagnosis of HIT over a 40-month period. Patients were assessed for the primary outcome of 30-day mortality, as well as baseline characteristics, development of thrombosis, and the economic impact of HIT. The primary outcome measure was 30-day mortality and occurred in 58 (16.6%) patients, 40 (15.3%) in the HIT group versus 18 (20.7%) in the HITT group (p = 0.25). The frequency of HIT was greater in patients exposed to UFH than in patients exposed to LMWH (0.8% vs. 0.2%, respectively, p < 0.001). Both HIT and HITT patients who were exposed to UFH had higher hospital costs than those exposed to LMWH (

Adjuvant Ketamine Analgesia for the Management of Cancer Pain

113,100 vs.

Calcium channel blockers as the treatment of choice for hypertension in renal transplant recipients: Fact or fiction

56,352, respectively, p < 0.001). HIT remains an important clinical problem with a high mortality rate and significant cost, regardless of development of thrombosis. Prospective controlled trials need to be conducted to determine the optimal strategy to reduce the frequency of HIT.

Evaluation of dexmedetomidine versus propofol-based sedation therapy in mechanically ventilated cardiac surgery patients at a tertiary academic medical center.

OBJECTIVE: To review the clinical literature evaluating the utilization of intravenous ketamine for the management of cancer-related pain, to summarize the data that suggest ketamine is an appropriate adjuvant method of providing analgesia and to report a case of successful pain management using ketamine in a patient with recurrent testicular cancer at our institution. DATA SOURCES: Primary literature was identified through a MEDLINE search (1966–March 2002), and additional information was obtained through secondary and tertiary sources. DATA SYNTHESIS: The available data suggest that supplementation of morphine with ketamine improves analgesia in patients with cancer, and also provides insight to the controversy regarding the efficacy and adverse effects of various ketamine doses. At subanesthetic doses, ketamine may be beneficial at reducing opioid requirements and related adverse effects. CASE SUMMARY: A 34-year-old white man with recurrent testicular cancer was admitted with radiating neuropathic pain of the legs and lower back. The patient was suspected to also be experiencing opioid adverse effects; therefore, alternative analgesic options were warranted. Ketamine was successful in reducing patient-reported pain and was also well tolerated. CONCLUSIONS: Ketamine is an adjuvant analgesic for the treatment of cancer-related pain when other agents either fail or are intolerable. Accordingly, there are several factors that may prevent adequate pain control with opioid use; therefore, alternative analgesic options should be considered. Promise exists for ketamine as a contemporary analgesic in the appropriate patient.

Azacitidine-induced interstitial and alveolar fibrosis in a patient with myelodysplastic syndrome.

Posttransplantation hypertension has been identified as an independent risk factor for chronic allograft dysfunction and loss. Based on available morbidity and mortality data, posttransplantation hypertension must be identified and managed appropriately. During the past decade, calcium channel blockers have been recommended by some as the antihypertensive agents of choice in this population, because it was theorized that their vasodilatory effects would counteract the vasoconstrictive effects of the calcineurin inhibitors. With increasing data becoming available, reexamining the use of traditional antihypertensive agents, including diuretics and β‐blockers, or the newer agents, angiotensin‐converting enzyme (ACE) inhibitors and angiotensin II receptor blockers, may be beneficial. Transplant clinicians must choose antihypertensive agents that will provide their patients with maximum benefit, from both a renal and a cardiovascular perspective. β‐Blockers, diuretics, and ACE inhibitors have all demonstrated significant benefit on morbidity and mortality in patients with cardiovascular disease. Calcium channel blockers have been shown to possess the ability to counteract cyclosporine‐induced nephrotoxicity. When compared with β‐blockers, diuretics, and ACE inhibitors, however, the relative risk of cardiovascular events is increased with calcium channel blockers. With the long‐term benefits of calcium channel blockers on the kidney unknown and a negative cardiovascular profile, these agents are best reserved as adjunctive therapy to β‐blockers, diuretics, and ACE inhibitors.