A stitch in time saves nine: timely use of N-acetyl cysteine (NAC) for chemotherapy-induced veno-occlusive disease (VOD)-is it a cost-effective alternative?

Chemotherapy-induced veno-occlusive disease (VOD) is a rare liver dysfunction seen among pediatric cancer patients which could lead to severe morbidity and mortality. Defibrotide is the commonly used antidote in the management of both stem cell transplant and chemotherapy-associated VOD along with liver supportive measures. Defibrotide is costly and generally not accessible to majority of patients treated at resource poor settings. In this report, we describe the successful management of chemotherapy-induced VOD with timely administration of N-acetyl cysteine.

Diagnostic imaging for the assessment of acquired abdominal vascular diseases in small animals: A pictorial review.

Advances in interventional radiology and surgical techniques now allow complex abdominal diseases to be more successfully treated in small animals. Abdominal vascular alterations, acquired as individual process or as complication of other lesions such as neoplasia, can be life-threatening or at least greatly limit curative interventions of underlying diseases. Computed tomography (CT) and high-definition ultrasonography are now readily available in veterinary referral centers. Yet, there is little information currently available on the use of these modalities for the diagnosis and characterization of these vascular alterations. The purpose of this article is to review the CT and ultrasonographic findings of acquired vascular diseases in the abdomen of dogs and cats, using both the veterinary and human medicine literature as references, and highlighting essential concepts through figures.

Comparative assessment of hypothalamic-pituitary-adrenal axis suppression secondary to intrabursal injection of different glucocorticoids: a pilot study.

BACKGROUND: Hypothalamic-pituitary-adrenal axis (HPAA) suppression is the most common and dangerous, although often unrecognized and untreated, side effect of glucocorticoid administration. The risk and duration depend both on patient and treatment characteristics. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) currently represents the gold standard method to evaluate the metabolism of endogenous and exogenous steroids. OBJECTIVE: To assess prevalence, severity, and duration of HPAA suppression subsequent to the injection of two steroids with equivalent potency but different pharmacokinetics. SUBJECTS AND METHODS: Single-blind randomized case-control pilot study. Forty patients (22 F; age 48.7 ± 7.2 years) with shoulder calcific tendinopathy received an intrabursal injection of 40 mg of 6α-methylprednisolone acetate (MA) or triamcinolone acetonide (TA). Just before (T0) and after 1 (T1), 7 (T2), 15 (T3), 30 (T4) and 45 (T5) days, we assessed morning blood cortisol and ACTH by RIA, and 24-h urinary levels of MA, TA and free cortisol by HPLC-MS/MS. RESULTS: HPAA function was normal at baseline. At T1, all patients presented HPAA suppression reaching the lowest cortisol, ACTH and UFC levels, that were similar between groups. At T2, mean cortisol remained lower than at baseline (p < 0.0001) in the TA group. In both groups, mean cortisol and ACTH levels progressively normalized, suggesting HPA recovery, except for three patients in the MA and two in the TA group. UFC levels remained lower than normal (p < 0.0001) up to T5, despite the disappearance of exogenous GCs. No patient developed manifestations of hypocortisolism. CONCLUSIONS: A single 40-mg intrabursal injection of MA or TA is sufficient to suppresses HPAA up to 45 days. Although typically asymptomatic, patients should be instructed to recognize and report symptoms suggestive for hypocortisolism, to provide prompt diagnosis, and eventually, treatment, thus avoiding severe complications.

18F-fluorodeoxyglucose positron emission tomography-based evaluation of systemic and vascular inflammation and assessment of the effect of systemic treatment on inflammation in patients with moderate-to-severe psoriasis: A randomized placebo-controlled pilot study.

BACKGROUND: Psoriasis is a systemic inflammatory disorder associated with an increased risk of cardiovascular disease. OBJECTIVE: To evaluate the utility of [[18]F]-fluorodeoxyglucose positron emission tomography/computed tomography in identifying vascular and systemic inflammation in psoriasis patients with moderate-to-severe disease and to analyze its usefulness in assessing the effect of systemic treatment. METHODS: This was a randomized, double-blind pilot study conducted in a tertiary care center. Baseline standardized uptake value score was estimated by18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with moderate-to-severe psoriasis and compared with historical controls. Patients were then randomized using computer-generated randomization list into methotrexate or placebo (with or without pioglitazone) groups.18F-fluorodeoxyglucose positron emission tomography/computed tomography was repeated at 12 weeks and composite standardized uptake value score determined. The correlation between Psoriasis Activity and Severity Index and SUVmax was assessed. RESULTS: A total of 16 patients were randomized to different treatment groups. Significant increase in mean SUVmax was observed in the ascending aorta in psoriasis patients as compared to historical controls (2.03 ± 0.53 vs 1.51 ± 0.36, P < 0.03). There was no difference in composite standardized uptake value score after 12 weeks of treatment in any of the treatment groups (P = 0.82), although an improvement in Psoriasis Activity and Severity Index score in the methotrexate arm was observed. No correlation was found between mean SUVmax and Psoriasis Activity and Severity Index scores in various aortic segments (r = 0.3-0.7). LIMITATIONS: Small sample size, short follow-up, historical controls, exclusion of patients with comorbid conditions and lack of surrogate markers of systemic inflammation. CONCLUSION: 18F-fluorodeoxyglucose positron emission tomography imaging showed higher vascular inflammation in ascending aorta of psoriasis patients as compared to historical controls. Systemic treatment with methotrexate and pioglitazone did not influence the vascular inflammation in the short term.

Mechanisms of vascular disease in dementia: what does industry want to know?

Despite recent advances in basic and clinical science, dementia remains an area of high unmet medical need. The role of cerebrovascular mechanisms in the pathogenesis and progression of cognitive and functional impairment in dementia is being revived. In order to facilitate the development of therapeutic approaches, it is critical that a number of fundamental elements are integrated into research strategies investigating cerebrovascular pathologies as these will maximize the opportunity of bringing medicines to patients in a timely manner.

Measuring Procedure and Maximal Hyperemia in the Assessment of Fractional Flow Reserve for Superficial Femoral Artery Disease.

AIM: The optimal fractional flow reserve (FFR) measurement method for superficial femoral artery (SFA) lesions remains to be established. We clarified the optimal measuring procedure for FFR for SFA lesions and investigated the necessary dose of papaverine for inducing maximal hyperemia in SFA lesions. METHODS: Forty-eight patients with SFA lesions who underwent measurement of peripheral FFR (pFFR: distal mean pressure divided by proximal mean pressure) after endovascular treatment by the contralateral femoral crossover approach were prospectively enrolled. In the pFFR measurement, a guide sheath was placed on top of the common iliac bifurcation and pressure equalization was performed. After advancing the pressure wire distal to the SFA lesion, sequential papaverine administration selectively to the affected common iliac artery was performed. RESULTS: There were no symptoms, electrocardiogram changes, and significant pressure drops at the guide sheath tip with increasing papaverine dose. pFFR changes following 20, 30, and 40 mg of papaverine were 0.87±0.10, 0.84±0.10, and 0.84±0.10, respectively (P＜0.001). Although not significantly different, pFFR decreased more in several patients at 30 mg of papaverine than at 20 mg. The pFFR at 40 mg of papaverine was almost similar to that at 30 mg of papaverine. The necessary papaverine dose was not changed according to sex and number of run-off vessels. CONCLUSIONS: The contralateral femoral crossover approach is useful in FFR measurement for SFA lesions, and maximal hyperemia is induced by 30 mg of papaverine.

[ASSESSMENT OF SPECIFIC PHARMACOLOGIC ACTIVITY OF UNIFUSOL ON ENDOTHELIUM DYSFUNCTION MODEL INDUCED BY N-NITRO-L-ARGININE METHYL ETHER.]

Specific pharmacologic activity of sodium-L-arginine succinate (unifusol) was studied on endothelium dysfunction model (EDM) in rats. EDM was induced by daily administration of N-nitro-L-arginine methyl ether (L-NAME). The effectiveness of experimental therapy with unifusol was assessed by changes in the arterial pressure level, duration of endothelium-dependent and -independent vasodilation, and the blood concentration of endothelial dysfunction markers including VEGF, NO, endothelin-I and the number of desquamated endotheliocytes. Administration of unifusol favors correction of blood vessel endothelium state manifested by normalization of its functional activity and reduction of the apoptosis of endotheliocytes. In addition, the obtained results unambiguously confirm considerable vasodilating and antihypertensive effects of unifusol.

[Medical treatment of chronic venous disease: evolution or involution?]. / Trattamento medico della malattia venosa cronica: evoluzione o involuzione?

Chronic venous disease (CVD) is an important clinical condition with substantial epidemiological implications and socio-economic repercussions. In the Western world the consequences of its high prevalence, the costs of diagnosis and therapy, the significant loss of working hours and the repercussions on patients'quality of life are well known. Pharmacotherapy for CVD has greatly developed over the last 40 years and largely used in the symptomatic treatment of CVD together with compression therapy and to make patients more comfortable. The clinical efficacy on the symptoms (feeling of heaviness, pain, paresthesia, heat and burning sensations, night cramps, etc.) has long been confirmed by Level III, IV and V evidence, but there are now Level I and II trials on specific drugs. For the bioflavonoids double-blind, randomised trials have used micronized purified flavonoid fraction; rutosides; escin; anthocyanosides; and synthetic calcium dobesilate. It was therefore surprising some recent difficulties in the use of this important treatment in health national system in Italy. In this up-date we use the method on evidence-based medicine from the medical literature. We have started a governance and economic analysis of the problem in Italy. Particular consideration was given to the evidence set out in review, meta-analysis, guidelines and Consensus Statements in this field. The evidence for pharmacological agents in the treatment of CVD suggests today a wide use in all CEAP classes.

Cholinergic and neuroprotective drugs for the treatment of Alzheimer and neuronal vascular diseases. II. Synthesis, biological assessment, and molecular modelling of new tacrine analogues from highly substituted 2-aminopyridine-3-carbonitriles.

The synthesis, biological assessment, and molecular modelling of new tacrine analogues 11-22 is described. Compounds 11-22 have been obtained by Friedländer-type reaction of 2-aminopyridine-3-carbonitriles 1-10 with cyclohexanone or 1-benzyl-4-piperidone. The biological evaluation showed that some of these molecules were good AChE inhibitors, in the nanomolar range, and quite selective regarding the inhibition of BuChE, the most potent being 5-amino-2-(dimethylamino)-6,7,8,9-tetrahydrobenzo[1,8-b]-naphthyridine-3-carbonitrile (11) [IC(50) (EeAChE: 14nM); IC(50) (eqBuChE: 5.2µM]. Kinetic studies on the easily available and potent anticholinesterasic compound 5-amino-2-(methoxy)-6,7,8,9-tetrahydrobenzo[1,8-b]-naphthyridine-3-carbonitrile (16) [IC(50) (EeAChE: 64nM); IC(50) (eqBuChE: 9.6µM] showed that this compound is a mixed-type inhibitor (K(i)=69.2nM) of EeAChE. Molecular modelling on inhibitor 16 confirms that this compound, as expected and similarly to tacrine, binds at the catalytic active site of EeAChE. The neuroprotective profile of molecules 11-22 has been investigated in SH-SY5Y neuroblastoma cells stressed with a mixture of oligomycin-A/rotenone. Compound 16 was also able to rescue by 50% cell death induced by okadaic acid in SH-SY5Y cells. From these results we conclude that the neuroprotective profile of these molecules is moderate, the most potent being compounds 12 and 17 which reduced cell death by 29%. Compound 16 does not affect ACh- nor K(+)-induced calcium signals in bovine chromaffin cells. Consequently, tacrine analogues 11-22 can be considered attractive therapeutic molecules on two key pharmacological targets playing key roles in the progression of Alzheimer, that is, cholinergic dysfunction and oxidative stress, as well as in neuronal cerebrovascular diseases.

Cumulative cost of prescription medication in outpatients with type 1 diabetes in Finland.

AIMS/HYPOTHESIS: We examined the 11-year cumulative outpatient cost of prescription medication in patients with type 1 diabetes by subgroups according to the presence of complications and duration of diabetes. METHODS: This longitudinal study included a nationally representative cohort of patients with type 1 diabetes (N = 3,717) from the Finnish Diabetic Nephropathy Study (FinnDiane). The data were linked to the Drug Prescription Register. The cumulative cost was calculated between 1998 and 2008. Information on complications was updated until 2008. Patients were divided into 10-year groups according to the duration of diabetes in 1998. Generalised linear mixed models under gamma distribution were used to evaluate the costs. RESULTS: Approximately 25% of the patients had macrovascular disease (MVD) and/or end-stage renal disease (ESRD). The adjusted cumulative cost of medications increased 56% when MVD was present compared with those without complications. In patients with ESRD or with both complications present the cost increased fourfold or 15-fold, respectively, when diabetes medications were excluded. The proportion of renal failure related medications (immunosuppressants, peritoneal dialytics and erythropoietin) accounted for more than 70% of these costs. The cost of diabetes medication was rather stable, irrespective of complication status or duration of diabetes. However, when complications were present these costs were markedly lower in all 10-year duration groups. CONCLUSIONS/INTERPRETATION: This study shows that ESRD has a great impact on outpatient prescription medication costs. Since no considerable differences were observed in the cost of diabetes medication, the increase was completely due to the cost of medications related to comorbidity.

Multipotent drugs with cholinergic and neuroprotective properties for the treatment of Alzheimer and neuronal vascular diseases. I. Synthesis, biological assessment, and molecular modeling of simple and readily available 2-aminopyridine-, and 2-chloropyridine-3,5-dicarbonitriles.

The synthesis, molecular modeling, and pharmacological analysis of new multipotent simple, and readily available 2-aminopyridine-3,5-dicarbonitriles (3-20), and 2-chloropyridine-3,5-dicarbonitriles (21-28), prepared from 2-amino-6-chloropyridine-3,5-dicarbonitrile (1) and 2-amino-6-chloro-4-phenylpyridine-3,5-dicarbonitrile (2) is described. The biological evaluation showed that some of these molecules were modest inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), in the micromolar range. The 2-amino (3, 4), and 2-chloro derivatives 21-23, 25, 26 were AChE selective inhibitors, whereas 2-amino derivatives 5, 14 proved to be selective for BuChE. Only inhibitor 24 was equipotent for both cholinesterases. Kinetic studies on compound 23 showed that this compound is a mixed-type inhibitor of AChE showing a K(i) of 6.33 microM. No clear SAR can be obtained form these data, but apparently, compounds bearing small groups such as the N,N'-dimethylamino or the pyrrolidino, regardless of the presence of a 2-amino, or 6-chloro substituent in the pyridine ring, preferentially inhibit AChE. Molecular modeling on inhibitors 4, 5, 22, and 23 has been carried out to give a better insight into the binding mode on the catalytic active site (CAS), and peripheral anionic site (PAS) of AChE. The most important differences in the observed binding relay on the modifications of the group at C2, as the amino group forms two hydrogen bonds that direct the binding mode, while in the case of compounds with a chlorine atom, this is not possible. The neuroprotective profile of these molecules has been investigated. In the LDH test, only compounds 26, 3, 22, and 24 showed neuroprotection with values in the range 37.8-31.6% in SH-SY5Y neuroblastoma cells stressed with a mixture of oligomycin-A/rotenone, but in the MTT test only compound 17 (32.9%) showed a similar profile. Consequently, these compounds can be considered as attractive multipotent therapeutic molecules on two key pharmacological receptors playing key roles in the progress of Alzheimer, that is, cholinergic dysfunction and oxidative stress, and neuronal vascular diseases.

Uninsured South Florida vascular surgery patients are less likely to receive optimal medical management than their insured counterparts.

OBJECTIVE: Vascular disease is the most prevalent condition in patients aged >60 years, leading to increasing complications associated with their comorbid conditions. Poor medical compliance could be one reason why the rate of complications may be higher in this patient population, particularly the uninsured. This study was conducted to better assess rates of medication compliance in vascular surgical patients. METHODS: Consecutive patients seen in vascular clinics at a busy tertiary academic center were prospectively studied. Physicians and physician assistants used a standardized questionnaire to collect patient data and evaluated patients for coexisting medical conditions and medication use. Optimal medical therapy was defined according to the 2006 American Heart Association (AHA)/American College of Cardiology (ACC) "Guidelines for Secondary Prevention for Atherosclerotic Vascular Disease." Data were analyzed using multivariate regression. RESULTS: During the 4-month study period, 180 consecutive patients (47% men) were seen in vascular surgery clinics. Most patients (79%) were nonsmokers and only 21% admitted to smoking. Comorbid conditions surveyed included hypertension in 141, diabetes mellitus in 56, coronary artery disease in 24, hypercholesterolemia in 89, and chronic renal failure in 13; of these, 61% were insured and 39% had no insurance. Overall, only 31% of all patients were receiving adequate medical therapy for their comorbid conditions, and about 66% were receiving suboptimal medical treatment for their vascular disease. Uninsured patients were less likely (19%) than insured patients (39%) to receive optimal medical therapy (P = .012). Lack of insurance was a predictor of suboptimal medical therapy for hypertension (odds ratio [OR], 3.13; 95% confidence interval [CI], 1.20-8.16; P = .016), hypercholesterolemia (OR, 5.1; 95% CI, 1.87-13.88; P = .001), peripheral arterial disease (OR, 13.32; 95% CI, 2.84-62.54, P < .001), and any disease overall (OR, 2.43; 95% CI, 1.21-4.88, P = .012). Overall, men and women were equally likely (68%) to receive suboptimal medical therapy; however, women were significantly more likely to be undertreated for coronary artery disease (OR, 0.022; 95% CI, 0.0017-0.293; P < .001). CONCLUSIONS: Compliance with optimal medical therapy for secondary risk factor management amongst our vascular surgery patients is low. Uninsured patients are less likely to receive optimal medical therapy than their insured counterparts. This survey provides sobering statistics regarding medical compliance in our population. This issue deserves further study and may indirectly affect outcomes in minority groups that are disproportionately represented in our uninsured patients.

A randomized, controlled clinical trial of ketoprofen for sickle-cell disease vaso-occlusive crises in adults.

Vaso-occlusive crisis (VOC) is the primary cause of hospitalization of patients with sickle-cell disease. Treatment mainly consists of intravenous morphine, which has many dose-related side effects. Nonsteroidal antiinflammatory drugs have been proposed to provide pain relief and decrease the need for opioids. Nevertheless, only a few underpowered trials of nonsteroidal antiinflammatory drugs for sickle-cell VOC have been conducted, and conflicting results were reported. We conducted a phase 3, double-blind, randomized, placebo-controlled trial with ketoprofen (300 mg/day for 5 days), a nonselective cyclooxygenase inhibitor, for severe VOC in adults. A total of 66 VOC episodes were included. The primary efficacy outcome was VOC duration. The secondary end points were morphine consumption, pain relief, and treatment failure. Seven VOC episodes in each group were excluded from the analysis because of treatment failures. No significant between-group differences were observed for the primary outcome or the secondary end points. Thus, although ketoprofen was well-tolerated, it had no significant efficacy as treatment of VOC requiring hospitalization. These findings argue against its systematic use in this setting.

Assessment of quality of life in Mexican patients suffering from chronic venous disorder - impact of oral Ruscus aculeatus-hesperidin-methyl-chalcone-ascorbic acid treatment - 'QUALITY Study'.

OBJECTIVES: The present study assessed the effect of Ruscus aculeatus-hesperidin-methyl-chalcone-ascorbic acid (HMC-AA) on the quality of life (QoL) of patients suffering from chronic venous disorders (CVDs). METHODS: An observational, multicentre and prospective study was performed with 917 Mexican patients suffering from CVD. Patients were treated with R. aculeatus-HMC-AA. After 12 weeks of treatment, the physicians then assessed the patients' symptoms and QoL using Short Form (SF-12) and Chronic Venous Insufficiency (CIVIQ) auto-questionnaires. RESULTS: Patients were mainly women (86.7%), overweight or obese (72.7%) or C2 (39.3%)-C3 (27.6%). All symptoms and ankle circumferences significantly improved over time, with increasing clinical, aetiological, anatomical and pathophysiological (CEAP) classes and body mass index (BMI) (P < 0.001). Concerning QoL, all dimensions of the SF-12 score significantly improved over time (P < 0.001). Moreover, the CIVIQ scores significantly improved (P < 0.001) with increasing BMI (P < 0.002) and CEAP classes (P < 0.05). CONCLUSION: R. aculeatus-HMC-AA significantly improved the symptoms and QoL of CVD patients.

The economic consequences of non-evidence-based clopidogrel use.

BACKGROUND: Clinical trials have helped clarify the efficacy of clopidogrel for the treatment and prevention of vascular disease. Costs for its use exceeded $5.9 billion in 2005, making it the second greatest source of drug expenditure in the world. However, little is known about the appropriateness of that use. Overuse of clopidogrel could have important implications for health care quality and drug expenditures. METHODS: We conducted a retrospective cohort study linking all filled prescriptions to all clinical encounter data for Medicare beneficiaries enrolled in a large state-wide pharmacy assistance program. We identified all patients newly prescribed clopidogrel during a recent 2-year period and determined the proportion who had indications for clopidogrel, the mean number of tablets filled by patients with and without apparent indications in the year after starting therapy, and the costs associated with the observed patterns of clopidogrel use. RESULTS: We identified 4977 patients who were newly prescribed clopidogrel. Of these patients, only 47% had > or = 1 documented indications for clopidogrel according to clinical trial findings. Using looser criteria, the number of patients with appropriate indications was 56%. During the first year of therapy, 43% ($2.05 million) of total clopidogrel expenditures for the patients studied was spent on patients without an indication that this agent was required, using the extended criteria for evidence-based use. CONCLUSIONS: More than 40% of the clopidogrel used in this population appears to have been prescribed to patients for whom the drug had no documented advantage over aspirin or no antiplatelet therapy. If the same proportion applies nationally, in 2005, it would represent almost $1.5 billion of potentially unnecessary health care expenditure.

START (screening tool to alert doctors to the right treatment)--an evidence-based screening tool to detect prescribing omissions in elderly patients.

BACKGROUND: Inappropriate prescribing encompasses acts of commission i.e. giving drugs that are contraindicated or unsuitable, and acts of omission i.e. failure to prescribe drugs when indicated due to ignorance of evidence base or other irrational basis e.g. ageism. There are considerable published data on the prevalence of inappropriate prescribing; however, there are no recent published data on the prevalence of acts of omission. The aim of this study was to calculate the prevalence of acts of prescribing omission in a population of consecutively hospitalised elderly people. METHODS: A screening tool (screening tool to alert doctors to the right treatment acronym, START), devised from evidence-based prescribing indicators and arranged according to physiological systems was prepared and validated for identifying prescribing omissions in older adults. Data on active medical problems and prescribed medicines were collected in 600 consecutive elderly patients admitted from the community with acute illness to a teaching hospital. On identification of an omitted medication, the patient's medical records were studied to look for a valid reason for the prescribing omission. RESULTS: Using the START list, we found one or more prescribing omissions in 57.9% of patients. In order of prevalence, the most common prescribing omissions were: statins in atherosclerotic disease (26%), warfarin in chronic atrial fibrillation (9.5%), anti-platelet therapy in arterial disease (7.3%) and calcium/vitamin D supplementation in symptomatic osteoporosis (6%). CONCLUSION: Failure to prescribe appropriate medicines is a highly prevalent problem among older people presenting to hospital with acute illness. A validated screening tool (START) is one method of systematically identifying appropriate omitted medicines in clinical practice.

Assessment of bleeding events in clinical trials--proposal of a new classification.

Present classifications of bleeding events used in antithrombotic and/or antiplatelet clinical trials are based on the criteria developed by the Thrombolysis In Myocardial Infarction (TIMI) and Global Use of Strategies to Open Coronary Arteries (GUSTO) groups. Introduced more than a decade ago, the 2 classifications used the criteria to better categorize hemorrhagic events after therapy with thrombolytic agents. Recent advances in interventional cardiology, resulting in a domination of percutaneous intracoronary procedures over systemic drug-induced thrombolysis, have substantially changed the clinical characteristics and magnitude of bleeding complications. Moreover, disturbances of the coagulation cascade, as well as platelet inhibition caused directly by antithrombotic and antiplatelet agents, share very specific and well-recognized clinical features not reflected in the existing classifications. Bleeding events after aspirin or clopidogrel, and especially those after more delicate antiplatelet regimens with dipyridamole used in patients after ischemic stroke or transient ischemic attack, are impossible to classify by the present guidelines, other than categorically triaging them altogether to the "minor" category. Uniting entirely different bleeding events as "minor" under-rates their importance and diminishes affiliated risks, creating an illusion that they do not require monitoring and/or changes in antiplatelet or antithrombotic regimens. In reality, such unrecognized and unreported mild complications may transform into more serious bleeds or lead to noncompliance. Unauthorized withdrawal from antiplatelet agents in turn causes rebound platelet activation and higher risk for secondary vascular events. In conclusion, a new classification of bleeding events is introduced (the BleedScore), based on a point accumulation depending on the severity of hemorrhage, which is believed to be more suitable for the assessment of modern, more delicate antithrombotic and antiplatelet therapies, particularly for their realistic assessment in clinical trials.