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An abstract of the bibliography article "Key Articles Related to Complementary and Alternative Medicine in Cardiovascular Disease: Part 1," by Sheryl L. Chow et al is presented.

Managing risk related to low-density lipoprotein (LDL) is vital in therapy for patients at risk for atherosclerotic cardiovascular disease (ASCVD) events given its important etiologic role in atherogenesis. Despite decades of research showing reduction of ASCVD risk with multiple approaches to lowering of LDL cholesterol, there continue to be significant gaps in care with inadequate numbers of patients receiving standard of care lipid-lowering therapy. Confusion regarding implementation of the multiple published clinical practice guidelines has been identified as one contributor to suboptimal management of LDL-related risk. This review summarizes the current guidelines for reduction of LDL-related cardiovascular risk provided by a number of major professional societies, which have broad applicability to diverse populations worldwide. Statements have varied in the process and methodology of development of recommendations, the grading system for level and strength of evidence, the inclusion or exclusion of expert opinion, the suggested ASCVD risk assessment tool, the lipoproteins recommended for risk assessment, and the lipoprotein targets of therapy. The similarities and differences among important guidelines in the United States and internationally are discussed, with recommendations for future strategies to improve consistency in approaches to LDL-related ASCVD risk and to reduce gaps in implementation of evidence-based therapies. [ABSTRACT FROM AUTHOR]

Despite advances in the management of heart failure ( HF), quality of life and other outcomes remain suboptimal for many patients. Anemia and iron deficiency are comorbidities associated with adverse outcomes, although their pathophysiology in the setting of HF is not entirely understood. Anemia and iron deficiency may exist independently and may be a consequence of the systemic inflammatory state characterized by chronic HF. However, it is unclear whether serum hemoglobin concentrations and other hematologic parameters serve as markers for the severity of disease or represent novel therapeutic targets. Research in this area has focused primarily on therapies known to be effective for these conditions in other chronic disease states with similar pathophysiologic features (e.g., end-stage renal disease). Despite its many practical advantages, minimal evidence exists to support the use of oral iron supplementation in this setting. In contrast, intravenous iron has been the subject of several recent investigations, demonstrating improvements in both surrogate and clinical end points, although benefits seem to be the most substantial in patients with concomitant anemia. Erythropoietin-stimulating agents demonstrated early promise in retrospective analyses and small prospective trials, but their benefit was outweighed by a lack of improvement in clinical outcomes and an excess number of thromboembolic events in the largest trial of patients with anemia and HF to date. For acute symptomatic anemia, blood transfusion may be considered, although few trials have included patients with HF, and caution must be exerted in those who are hemodynamically unstable. Based on the currently available evidence, treatment of iron deficiency appears to confer benefit in patients with HF, whereas strategies aimed at improving hemoglobin alone do not. Included is a review of the pathophysiology of these conditions in the setting of HF, clinical trials evaluating pharmacologic therapy, and recommendations for management. [ABSTRACT FROM AUTHOR]

The purpose of this manuscript is to review the clinical entity of dry eye syndrome (DES) and to provide a scientific basis and rationale for the usage of thymosin beta 4 (Tβ4) as a novel therapy for DES. DES is a common disorder affecting an estimated 25-30 million people in the United States alone and is characterized by inflammation of the ocular surface. Consequently, patients can suffer from burning, irritation, severe discomfort, foreign body sensation, and blurry and decreased vision. Recent animal studies of DES demonstrate that Tβ4 eye drops significantly reduce corneal fluorescein staining, indicating improved wound healing. Based on previous studies, there is clear support for further clinical investigation and development of Tβ4 as a novel, safe, and effective agent to treat dry eye. Herein, we discuss the scientific and clinical rationales that make Tβ4 a potential ideal candidate therapeutic for DES. [ABSTRACT FROM AUTHOR]

Purpose: To identify recipient factors that may be related to risk of corneal graft failure. Design: Multicenter, prospective, double-masked, controlled clinical trial. Participants: One thousand ninety subjects undergoing corneal transplantation for a moderate-risk condition (principally Fuchs'' dystrophy or pseudophakic corneal edema). Methods: Donor corneas were assigned using a random approach without respect to recipient factors, and surgeons were masked to information about the donor cornea, including donor age. Surgery and postoperative care were performed according to the surgeons'' usual routines, and subjects were followed up for 5 years. Baseline factors were evaluated for their association with graft failure. Main Outcome Measures: Graft failure, defined as a regraft or a cloudy cornea that was sufficiently opaque to compromise vision for a minimum of 3 consecutive months. Results: Preoperative diagnosis of pseudophakic or aphakic corneal edema increased graft failure risk approximately 4-fold compared with Fuchs'' dystrophy (27% vs. 7%). Prior glaucoma surgery with preoperative glaucoma medication use substantially increased the graft failure rate. Factors not strongly associated with graft failure included age, gender, diabetes, smoking, and graft size. Conclusions: The risk of graft failure is significantly increased in eyes with pseudophakic or aphakic corneal edema compared with Fuchs'' dystrophy, independent of lens status, and in eyes with a history of glaucoma. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

This compilation is part of a series of articles identifying important literature in cardiovascular pharmacotherapy. This bibliography focuses on pharmacotherapeutic management of acute decompensated and chronic heart failure and provides an update of the heart failure bibliography published in Pharmacotherapy in 2004. Most of the cited works present the results of landmark clinical studies that have shaped the management of patients with heart failure. Limited primary literature is available for some topics, thus pertinent review articles are also listed. In addition, consensus documents formed by expert panels are reviewed. This compilation may serve as a teaching tool, reference resource, or update of the literature for pharmacy clinicians, physicians, and students. [ABSTRACT FROM AUTHOR]

The Accreditation Council for Pharmacy Education issued revised standards ( Standards 2007) for professional programs leading to the Doctor of Pharmacy degree in July 2007. The new standards require colleges and schools of pharmacy to provide pharmacy practice experiences that include direct interaction with diverse patient populations. These experiences are to take place in multiple practice environments (e.g., community, ambulatory care, acute care medicine, specialized practice areas) and must include face-to-face interactions between students and patients, and students and health care providers. In 2009, the American College of Clinical Pharmacy ( ACCP) identified concerns among their members that training for some students during the fourth year of pharmacy curriculums are essentially observational experiences rather than encounters where students actively participate in direct patient care activities. These ACCP members also stated that there is a need to identify effective mechanisms for preceptors to balance patient care responsibilities with students' educational needs in order to fully prepare graduates for contemporary, patient-centered practice. The 2010 ACCP Educational Affairs Committee was charged to provide recommendations to more effectively foster the integration of pharmacy students into direct patient care activities during advanced pharmacy practice experiences ( APPEs). In this commentary, the benefits to key stakeholders (pharmacy students, APPE preceptors, clerkship sites, health care institutions, academic pharmacy programs) of this approach are reviewed. Recommendations for implementation of direct patient care experiences are also provided, together with discussion of the practical issues associated with delivery of effective APPE. Examples of ambulatory care and acute care APPE models that successfully integrate pharmacy students into the delivery of direct patient care are described. Enabling students to engage in high-quality patient care experiences and to assume responsibility for drug therapy outcomes is achievable in a variety of practice settings. In our opinion, such an approach is mandatory if contemporary pharmacy education is to be successful in producing a skilled workforce capable of affecting drug therapy outcomes. [ABSTRACT FROM AUTHOR]

The utilization of complementary and alternative medicine (CAM) has increased over the past several years, largely based on unsubstantiated benefits and aggressive marketing. However, the safety of nontraditional products is often overlooked and undocumented. Clinicians should become familiar with the potential risks of CAM and inform patients about associated adverse effects and/or serious drug interactions. This bibliography paper compiled key articles specific to CAM therapy and cardiovascular disease, which include primary literature and review articles. Based on the numerous published reports available on this topic, this bibliography, as part 2 of 2, focuses on the safety of CAM therapy in cardiovascular disease. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review sought to define the mechanism of the drug-drug interaction between phosphodiesterase-type-5 (PDE-5) inhibitors and organic nitrates as well as the clinical impact and recommended management across different clinical scenarios., Recent Findings: This drug-drug interaction results in hemodynamically significant hypotension during episodic PDE-5 use and acute nitrate administration mainly during cardiovascular emergencies with multiple studies describing the expected impact. Chronic co-administration of long-acting nitrates and PDE-5 inhibitors has been observed in practice in a small percentage of patients despite the labeled contraindication without noted adverse effects. Acute nitrate therapy should be avoided in the context of episodic PDE-5 exposure, likely identified through systematic processes. Few data exist defining risk with lower-intensity daily PDE-5 administration. Chronic co-administration is not recommended but may be navigated with careful risk-benefit determination. Future directions also aim to identify potential areas where nitrate synergy may achieve clinical benefit., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Abstract: Iron deficiency is common in patients with heart failure and has been associated with worse outcomes, including increases in mortality, disease progression, and hospitalizations. As such, several studies have evaluated the role of iron supplementation in mitigating these risks. Evidence for the role of intravenous iron in improving exercise capacity, quality of life, and hospitalizations is promising, although the benefits of oral iron remain less clear. This review will evaluate the literature surrounding iron supplementation in heart failure and provide practical recommendations for its management., Competing Interests: S. E. Gale—consultant for Pharmacosmos (ended in August 2021). The remaining authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Gout is a common comorbidity in heart failure (HF) patients and is frequently associated with acute exacerbations during treatment for decompensated HF. Although colchicine is often used to manage acute gout in HF patients, its impact on clinical outcomes when used during acute decompensated HF is unknown., Methods: This was a single center, retrospective study of hospitalized patients treated for an acute HF exacerbation with and without acute gout flare between March 2011 and December 2020. We assessed clinical outcomes in patients treated with colchicine for a gout flare compared to those who did not experience a gout flare or receive colchicine. The primary outcome was in-hospital all-cause mortality., Results: Among 1047 patient encounters for acute HF during the study period, there were 237 encounters (22.7%) where the patient also received colchicine for acute gout during admission. In-hospital all-cause mortality was significantly reduced in the colchicine group compared with the control group (2.1% vs. 6.5%, p = .009). The colchicine group had increased length of stay (9.93 vs. 7.96 days, p < .001) but no significant difference in 30-day readmissions (21.5% vs. 19.5%, p = .495). In a Cox proportional hazards model adjusted for age, inpatient colchicine use was associated with improved survival to discharge (hazards ratio [HR] 0.163, 95% confidence interval [CI] 0.051-0.525, p = .002) and a reduced rate of in-hospital CV mortality (HR 0.184, 95% CI 0.044-0.770, p = .021)., Conclusion: Among patients with a HF exacerbation, treatment with colchicine for a gout flare was associated with significantly lower in-hospital mortality compared with those not treated for acute gout., (© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Anticoagulation of patients treated with the Impella percutaneous mechanical circulatory support (MCS) devices is complex and lacks consistency across centers, potentially increasing the risk of complications. In order to optimize safety and efficacy, an expert committee synthesized all available evidence evaluating anticoagulation for patients receiving Impella support in order to provide consensus recommendations for the management of anticoagulation with these devices. The evidence synthesis led to the creation of 42 recommendations to improve anticoagulation management related to the use of the Impella devices. Recommendations address purge solution management, intravenous anticoagulation, monitoring, evaluation and management of heparin-induced thrombocytopenia (HIT), and management during combination MCS support. The use of a heparinized, dextrose-containing purge solution is critical for optimal device function, and a bicarbonate-based purge solution may be an alternative in certain situations. Likewise, intravenous (ie, systemic) anticoagulation with heparin is often necessary, although evidence supporting the optimal assay and target range for monitoring the level of anticoagulation is generally lacking. Patients treated with an Impella MCS device may develop HIT, which is more difficult to evaluate and treat in this setting. Lastly, the use of Impella with extracorporeal membrane oxygenation or for biventricular support creates additional anticoagulation challenges., (© 2021 Pharmacotherapy Publications, Inc.)

Purpose: To identify donor and recipient factors, including eye bank tissue observations, predictive of operative complications in the Cornea Preservation Time Study., Methods: One thousand three hundred thirty study eyes undergoing Descemet stripping automated endothelial keratoplasty for Fuchs dystrophy or pseudophakic/aphakic corneal edema were randomized to receive a donor cornea with preservation time (PT) of 0 to 7 days (N = 675) or 8 to 14 days (N = 655). Donor factors included demographics, prelamellar corneal and postlamellar lenticule dissection thickness, central endothelial cell density, and tissue processing time. Recipient factors included demographics, intraocular pressure, and glaucoma medications or surgery (trabeculectomy, laser trabeculoplasty). Eye bank observations included donor tissue folds, pleomorphism/polymegethism, and endothelial cell abnormalities. Possible tissue-related operative complications were recorded including difficult donor lenticule unfolding and positioning. Multivariable logistic regression with backward selection was used to identify statistically significant (P < 0.01) associations between factors and operative complications., Results: The only factor predictive of operative complications [58 (4.4%) of 1330 surgeries] was prelamellar dissection donor corneal thickness (P = 0.002). For every 50 μm of donor corneal thickness prior to lamellar dissection, operative complication odds increased by 40% (odds ratio [99% confidence interval (CI)]: 1.40 [1.06-1.83]) adjusting for PT and whether the epithelium was on or off. The estimated mean prelamellar dissection donor corneal thickness for PT 0 to 7 days was 537 μm (99% CI: 516 μm-558 μm) compared with 567 μm (99% CI: 546 μm-588 μm) for PT 8 to 14 days (P < 0.001)., Conclusions: Thicker donor tissue (prelamellar dissection) is associated with operative complications and should be considered in tissue selection for Descemet stripping automated endothelial keratoplasty lenticule preparation.

Importance: Demonstrating that endothelial cell loss following Descemet stripping automated endothelial keratoplasty (DSAEK) is independent of donor cornea preservation time (PT) could increase the pool of corneal tissue available for keratoplasty., Objective: To determine whether endothelial cell loss 3 years after successful DSAEK is related to PT., Design, Setting, and Participants: A multicenter, double-masked, randomized clinical trial included 40 clinical sites (70 surgeons) in the United States, with donor corneas provided by 23 US eye banks. A total of 945 eyes of 769 participants were included in the Cornea Preservation Time Study that had not experienced graft failure 3 years after DSAEK, performed primarily for Fuchs endothelial corneal dystrophy (96% of the cohort). The study was conducted from April 16, 2012, to June 5, 2017., Interventions: DSAEK with random assignment of a donor cornea with PT of 0 to 7 days (0-7d PT) or 8 to 14 days (8-14d PT)., Main Outcomes and Measures: Endothelial cell density (ECD) at 3 years determined by a central image analysis reading center from clinical specular or confocal central endothelial images., Results: Nine hundred forty-five eyes of 769 participants (median age, 70 years [range, 42-90 years], 60.8% women, 93.0% white) in the Cornea Preservation Time Study that had not experienced graft failure 3 years after DSAEK were included. At the initial eye bank tissue screening, mean (SD) central ECD was 2746 (297) cells/mm2 in the 0-7d PT group (n = 485) and 2723 (284) cells/mm2 in the 8-14d PT group (n = 460). At 3 years, the mean (SD) ECD decreased from baseline by 37% (21%) in the 0-7d PT group and 40% (22%) in the 8-14d PT group to 1722 (626) cells/mm2 and 1642 (631) cells/mm2, respectively (mean difference, 73 cells/mm2; 95% CI, 8-138 cells/mm2; P = .03). When analyzed as a continuous variable (days), longer PT was associated with lower ECD (mean difference by days, 15 cells/mm2; 95% CI, 4-26 cells/mm2; P = .006). Endothelial cell loss (ECL) was comparable from 4 to 13 days’ PT (n = 878; 36%-43% when tabulated by day). Available extension study ECD results at 4 years mirrored those at 3 years in the 203 eyes in the 0-7d PT group (mean [SD] ECD, 1620 [673] cells/mm2 and mean [SD] ECL, 41% [23%]) and 209 eyes in the 8-14d PT group (mean [SD] ECD, 1537 [683] cells/mm2 and mean [SD] ECL, 44% [23%]) (mean difference, 112 cells/mm2; 95% CI, 5-219 cells/mm2; P = .04)., Conclusions and Relevance: Although ECL 3 years after Descemet stripping automated endothelial keratoplasty is greater with longer PT, the effect of PT on ECL is comparable from 4 to 13 days’ PT.

Importance: Demonstrating that success of Descemet stripping automated endothelial keratoplasty is similar across donor cornea preservation times (PTs) could increase the donor pool., Objective: To determine whether the 3-year rate of graft success using corneal donor tissue preserved 8 to 14 days is noninferior to that of donor tissue preserved 7 days or less., Design, Setting, and Participants: A multicenter, double-masked, randomized noninferiority clinical trial was conducted from April 16, 2012, to June 5, 2017, at 40 clinical sites (70 surgeons) in the United States, with donor corneas provided by 23 US eye banks. A total of 1090 individuals (1330 study eyes) underwent Descemet stripping automated endothelial keratoplasty (1255 eyes [94.4%] for Fuchs endothelial corneal dystrophy)., Interventions: Descemet stripping automated endothelial keratoplasty with random assignment of a donor cornea with a PT of 7 days or less (0-7d PT) or 8 to 14 days (8-14d PT)., Main Outcomes and Measures: Graft success at 3 years., Results: Of the 1090 participants (1330 study eyes; 60.2% women and 39.8% men; median age at enrollment, 70 years [range, 42-90 years]), the 3-year cumulative probability of graft success was 95.3% (95% CI, 93.6%-96.9%) in the 0-7d PT group and 92.1% (95% CI, 89.9%-94.2%) in the 8-14d PT group (difference, 3.2%). The upper limit of the 1-sided 95% CI on the difference was 5.4%, exceeding the prespecified noninferiority limit of 4%. The difference was mostly owing to more primary donor failures in the 8-14d PT group, with the conditional probability of failure after the first month being 2.4% in the 0-7d PT group and 3.1% in the 8-14d PT group. In preplanned secondary analyses, longer PT was associated with a lower rate of graft success (unadjusted hazard ratio for graft failure per additional day of PT, 1.10; 95% CI, 1.03-1.18; P = .008 [PT analyzed as days]), with success rates of 96.5% (95% CI, 92.3%-98.4%) for PT of 4 days or less, 94.9% (95% CI, 92.5%-96.6%) for PT of 5 to 7 days, 93.8% (95% CI, 91.0%-95.8%) for PT of 8 to 11 days, and 89.3% (95% CI, 84.4%-92.7%) for PT of 12 to 14 days (P = .01 [PT analyzed as categorical variable])., Conclusions and Relevance: The 3-year success rate in eyes undergoing Descemet stripping automated endothelial keratoplasty was high irrespective of PT. However, the study was unable to conclude that the success rate with donor corneas preserved 8 to 14 days was similar to that of corneas preserved 7 days or less with respect to the prespecified noninferiority limit. Although longer PT was associated with a lower success rate, the difference in rates was small when PT was less than 12 days.

Amiodarone remains the mostly frequently used antiarrhythmic in clinical practice and is most often used to maintain normal sinus rhythm in patients with atrial fibrillation who have failed a rate control strategy. Amiodarone has superior efficacy over other antiarrhythmics, a lower risk of torsade de pointes, and a better cardiovascular safety profile in patients with structural heart disease. However, amiodarone is associated with notable noncardiac toxicities affecting the thyroid, lungs, eyes, liver, and central nervous system. Since 2000, clinicians have been advised to follow amiodarone monitoring guidelines provided by the Heart Rhythm Society. Adherence to these recommendations in clinical practice, however, is suboptimal. Pharmacists play a major role in ensuring the safe and effective use of medications, particularly high-risk medications such as amiodarone. This qualitative review details the evidence supporting the role of pharmacist-led amiodarone monitoring services (AMS) in improving adherence to amiodarone monitoring guidelines and identifying adverse effects. Five studies were identified, and, overall, these programs had a favorable impact on improving adherence to guideline-recommended monitoring standards for amiodarone. The available evidence is limited by the significant variations in study designs and outcome definitions, lack of patient randomization, and limited generalizability. Nevertheless, available studies suggest that pharmacist-led AMS may improve adherence to recommended monitoring guidelines and identification of amiodarone-related adverse effects. Further study is warranted to demonstrate whether these services impact the overall quality of care provided to patients receiving amiodarone, which may justify broader implementation., (© 2016 Pharmacotherapy Publications, Inc.)

Purpose: The aim of this study was to assess the effect of donor and recipient factors on corneal allograft rejection and evaluate whether a rejection event was associated with graft failure., Methods: One thousand ninety subjects undergoing penetrating keratoplasty for a moderate risk condition (principally Fuchs dystrophy or pseudophakic corneal edema) were followed for up to 12 years. Associations of baseline recipient and donor factors with the occurrence of a rejection event were assessed in univariate and multivariate proportional hazards models., Results: Among 651 eyes with a surviving graft at 5 years, the 10-year graft failure (±99% confidence interval) rates were 12% ± 4% among eyes with no rejection events in the first 5 years, 17% ± 12% in eyes with at least 1 probable, but no definite rejection event, and 22% ± 20% in eyes with at least 1 definite rejection event. The only baseline factor significantly associated with a higher risk of definite graft rejection was a preoperative history of glaucoma, particularly when previous glaucoma surgery had been performed and glaucoma medications were being used at the time of transplant (10-year incidence 35% ± 23% compared with 14% ± 4% in eyes with no history of glaucoma/intraocular pressure treatment, P = 0.008)., Conclusions: Patients who experienced a definite rejection event frequently developed graft failure raising important questions as to how we might change acute and long-term corneal graft management. Multivariate analysis indicated that previous use of glaucoma medications and glaucoma filtering surgery was a significant risk factor related to a definite rejection event.

Platelet activation results in the release and upregulation of mediators responsible for immune cell activation and recruitment, suggesting that platelets play an active role in immunity. Animal models and retrospective data have demonstrated benefit of antiplatelet therapy on inflammatory mediator expression and clinical outcomes. This study sought to characterize effects of clopidogrel on the incidence and severity of community-acquired pneumonia (CAP). A retrospective cohort study was conducted of Kentucky Medicaid patients (2001-2005). The exposed cohort consisted of patients receiving at least six consecutive clopidogrel prescriptions; the non-exposed cohort was comprised of patients not prescribed clopidogrel. Primary endpoints included incidence of CAP and inpatient treatment. Secondary severity endpoints included mortality, intensive care unit admission, mechanical ventilation, sepsis, and acute respiratory distress syndrome/acute lung injury. CAP incidence was significantly greater in the exposed cohort (OR 3.39, 95% CI 3.27-3.51, p < 0.0001) that remained after adjustment (OR 1.48, 95% CI 1.41-1.55, p < 0.0001). Inpatient treatment was more common in the exposed cohort (OR 1.96, 95% CI 1.85-2.07, p < 0.0001), but no significant difference remained after adjustment. Trends favoring the exposed cohort were found for the secondary severity endpoints of mechanical ventilation (p = 0.07) and mortality (p = 0.10). Pooled analysis of published studies supports these findings. While clopidogrel use may be associated with increased CAP incidence, clopidogrel does not appear to increase--and may reduce--its severity among inpatients. Because this study was retrospective and could not quantify all variables (e.g., aspirin use), these findings should be explored prospectively.

Patients presenting for invasive cardiovascular procedures are frequently taking a variety of medications aimed to treat risk factors related to heart and vascular disease. During the procedure, antithrombotic, sedative, and analgesic medications are commonly needed, and after interventional procedures, new medications are often added for primary and secondary prevention of ischemic events. In addition to these prescribed medications, the use of over-the-counter drugs and supplements continues to rise. Most elderly patients, for example, are taking 5 or more prescribed medications and 1 or more supplements, and they often have some degree of renal insufficiency. This polypharmacy might result in drug-drug interactions that affect the balance of thrombotic and bleeding events during the procedure and during long-term treatment. Mixing of anticoagulants, for instance, might lead to periprocedural bleeding, and this is associated with an increase in long-term adverse events. Furthermore, the range of possible interactions with thienopyridine antiplatelets is of concern, because these drugs are essential to immediate and extended interventional success. The practical challenges in the field are great-some drug-drug interactions are likely present yet not well understood due to limited assays, whereas other interactions have well-described biological effects but seem to be more theoretical, because there is little to no clinical impact. Interventional providers need to be attentive to the potential for drug-drug interaction, the associated harm, and the appropriate action, if any, to minimize the potential for medication-related adverse events. This review will focus on drug-drug interactions that have the potential to affect procedural success, either through increases in immediate complications or compromising longer-term outcome., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Antiplatelet therapy is of paramount importance in the treatment and prevention of adverse cardiovascular events and stroke. Drug-drug interactions (DDIs) among antiplatelet therapies have been growing in both prevalence and clinical importance. Most DDIs with antiplatelet therapies are pharmacodynamic in nature. DDIs with thienopyridines and proton pump inhibitors have resulted in advisories from regulatory agencies although the full significance of this interaction is unknown. Other DDIs with thienopyridines may potentially exist with statins, calcium channel blockers, and warfarin but lack demonstratable evidence of harm. Aspirin may interact with a variety of medications, including non-steroidal anti-inflammatory agents and angiotensin inhibitors. DDIs requiring some level of intervention may also be present with dipyridamole and cilostazol. Overall, DDIs with antiplatelet drugs are biologically plausible and potentially clinically relevant. However, the full significance of these DDIs is largely unknown due to reliance on research of voluntary reports, registries, and claims databases to determine significance.

Neurotrophic corneal defects are difficult to heal and all too often lead to scarring and vision loss. Medical management is often of limited success. We describe the results of nine patients (ages 37-84) with chronic nonhealing neurotrophic corneal epithelial defects who were treated with thymosin beta 4 (Tbeta4) sterile eye drops for 28 or 49 days with a follow-up period of 30 days. Those with geographic defects (six patients) showed dramatic healing without clinically significant neovascularization. Stromal thinning was observed in one patient. Three patients with punctate epithelial defects did not have a demonstrable change in their clinical findings. Reduced ocular irritation was reported by all patients soon after treatment initiation. Results from these compassionate use cases indicate that Tbeta4 may provide a novel, topical approach to wound healing in chronic nonhealing neurotrophic corneal ulcers.

The European Medicines Agency (EMEA) recently issued a public statement on a possible interaction between clopidogrel and proton pump inhibitors (PPIs) and recommended that the product information for all medicines containing clopidogrel be amended to discourage concomitant use of PPIs unless absolutely necessary. This follows a prior alert issued by the United States Food and Drug Administration (FDA) earlier this year, stating that PPIs might interfere with the effectiveness of clopidogrel and that clinicians should reevaluate starting or continuing treatment with a PPI in patients taking clopidogrel. However, several experts have voiced their concern that the clopidogrel-PPI interaction has been given undue importance, given that all clinical studies suggesting this problem are observational. In this review, we critically analyze the available data and make practical suggestions for the clinician regarding appropriate use of PPIs in patients receiving clopidogrel. Based on currently available evidence, we suggest that the decision to prescribe a PPI to a patient on clopidogrel must be made on an individual patient basis balancing the gastrointestinal risk with the possible thrombotic risk and that PPIs should only be used for truly appropriate indications.

Purpose: To determine whether corneal graft survival over a 5-year follow-up period was affected by ABO blood type compatibility in participants in the Cornea Donor Study undergoing corneal transplantation principally for Fuchs dystrophy or pseudophakic corneal edema, conditions at low-risk for graft rejection., Design: Multi-center prospective, double-masked, clinical trial., Methods: ABO blood group compatibility was determined for 1,002 donors and recipients. During a 5-year follow-up period, episodes of graft rejection were documented, and graft failures were classified as to whether or not they were attributable to immunologic rejection. Endothelial cell density was determined by a central reading center for a subset of subjects., Results: ABO donor-recipient incompatibility was not associated with graft failure attributable to any cause including graft failure because of rejection, or with the occurrence of a rejection episode. The 5-year cumulative incidence of graft failure attributable to rejection was 32 (6%) for recipients with ABO recipient-donor compatibility and 12 (4%) for those with ABO incompatibility (hazard ratio, 0.65; 95% confidence interval, 0.33 to 1.25; P = .20). The 5-year incidence for a definite rejection episode, irrespective of whether graft failure ultimately occurred, was 64 (12%) for ABO compatible compared with 25 (8%) for ABO incompatible cases (P = .09). Among clear grafts at 5 years, percent loss of endothelial cells was similar in ABO compatible and incompatible cases., Conclusions: In patients undergoing penetrating keratoplasty for Fuchs dystrophy or pseudophakic corneal edema, ABO matching is not indicated since ABO incompatibility does not increase the risk of transplant failure attributable to graft rejection.

Nutrition impairment commonly occurs in patients with heart failure and affects disease progression. Vitamin and mineral deficiencies are associated with early mortality, particularly in patients classified as cachectic. Guideline-based therapies approved for heart failure, such as loop diuretics, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, aldosterone antagonists, and beta-adrenergic blockers, can lead to electrolyte abnormalities and predispose to some vitamin and micronutrient deficits. Clinical trial evidence in support of supplementary vitamin and mineral therapies for heart failure patients is limited with the exception of documented calcium and possibly vitamin D, thiamine, and coenzyme Q10 deficiencies. This area is gaining significant attention, and research is ongoing. The clinician can help minimize morbidity from nutrition impairment through appropriate monitoring and correction of baseline and medication-induced electrolyte imbalances, in addition to vitamin and mineral supplementation when appropriate.

Objective: To determine whether endothelial cell loss 5 years after successful corneal transplantation is related to the age of the donor., Design: Multicenter, prospective, double-masked clinical trial., Participants: Three hundred forty-seven subjects participating in the Cornea Donor Study who had not experienced graft failure 5 years after corneal transplantation for a moderate-risk condition (principally Fuchs' dystrophy or pseudophakic corneal edema)., Testing: Specular microscopic images of donor corneas obtained before surgery and postoperatively at 6 months, 12 months, and then annually through 5 years were submitted to a central reading center to measure endothelial cell density (ECD)., Main Outcome Measure: Endothelial cell density at 5 years., Results: At 5 years, there was a substantial decrease in ECD from baseline for all donor ages. Subjects who received a cornea from a donor 12 to 65 years old experienced a median cell loss of 69% in the study eye, resulting in a 5-year median ECD of 824 cells/mm(2) (interquartile range, 613-1342), whereas subjects who received a cornea from a donor 66 to 75 years old experienced a cell loss of 75%, resulting in a median 5-year ECD of 654 cells/mm(2) (interquartile range, 538-986) (P [adjusted for baseline ECD] = 0.04). Statistically, there was a weak negative association between ECD and donor age analyzed as a continuous variable (r [adjusted for baseline ECD] = -0.19; 95% confidence interval, -0.29 to -0.08)., Conclusions: Endothelial cell loss is substantial in the 5 years after corneal transplantation. There is a slight association between cell loss and donor age. This finding emphasizes the importance of longer-term follow-up of this cohort to determine if this relationship affects graft survival.

Objective: To determine whether graft survival over a 5-year follow-up period using corneal tissue from donors older than 65 is similar to graft survival using corneas from younger donors., Design: Multicenter prospective, double-masked, controlled clinical trial., Participants: One thousand ninety subjects undergoing corneal transplantation for a moderate-risk condition (principally Fuchs' dystrophy or pseudophakic corneal edema); 11 subjects with ineligible diagnoses were not included., Methods: Forty-three participating eye banks provided corneas from donors in the age range of 12 to 75 with endothelial cell densities of 2300 to 3300 cells/mm(2), using a random approach without respect to recipient factors. The 105 participating surgeons at 80 sites were masked to information about the donor cornea including donor age. Surgery and postoperative care were performed according to the surgeons' usual routines. Subjects were observed for 5 years., Main Outcome Measures: Graft failure, defined as a regraft or a cloudy cornea that was sufficiently opaque as to compromise vision for a minimum of 3 consecutive months., Results: The 5-year cumulative probability of graft survival was 86% in both the <66.0 donor age group and the >/=66.0 donor age group (difference = 0%, upper limit of 1-sided 95% confidence interval = 4%). In a statistical model with donor age as a continuous variable, there was no significant relationship between donor age and outcome (P = 0.11). Three graft failures were due to primary donor failure, 8 to uncorrectable refractive error, 48 to graft rejection, 46 to endothelial decompensation (23 of which had a prior, resolved episode of probable or definite graft rejection), and 30 to other causes. Distributions of the causes of graft failure did not differ between donor age groups., Conclusions: Five-year graft survivals for cornea transplants at moderate risk for failure are similar using corneas from donors >/= 66.0 years and donors < 66.0. Surgeons and patients now have evidence that corneas comparable in quality to those used in this study from donors through age 75 are suitable for transplantation.