INTRAVENOUS THROMBOLYTIC THERAPY FOR ACUTE NONARTERITIC CENTRAL RETINAL ARTERY OCCLUSION. A REVIEW.

Central retinal artery occlusion (CRAO) is a form of acute ischemic stroke. It is a critical condition that often leads to severe visual loss or blindness and can be a harbinger of further cerebrovascular events. Due to the lack of scientific data, there are no effective evidence-based forms of therapy for this condition. None of the conservative therapies have proven effective. The results of some previously published studies suggest a benefit of intravenous thrombolytic therapy in the same regimen as in the treatment of ischemic stroke. This work aims to present an overview of published clinical studies focused on the use of intravenous thrombolysis for CRAO, evaluate its efficacy and safety, and propose an optimal diagnostic and therapeutic algorithm for acute management of CRAO. Summary statistics of patient data from relevant studies indicate that a significant visual acuity improvement was achieved by a total of 45 % of patients receiving alteplase within 4.5 hours of symptoms onset. The occurrence of adverse events in this time window was not significant. Intravenous thrombolytic therapy in CRAO thus appears to be effective and safe. However, we still lack data from adequate prospective randomized controlled trials to confirm this conclusion. To date, two randomized trials are being conducted. The intravenous thrombolysis administration, patient monitoring, etiologic workup, and setting of effective secondary prevention should be ensured at the centre of highly specialized cerebrovascular care. Urgent transport of the CRAO patient to the nearest centre is essential.

INTRAVENOUS THROMBOLYTIC THERAPY FOR ACUTE NONARTERITIC CENTRAL RETINAL ARTERY OCCLUSION. A REVIEW.

Central retinal artery occlusion (CRAO) is a form of acute ischemic stroke. It is a critical condition that often leads to severe visual loss or blindness and can be a harbinger of further cerebrovascular events. Due to the lack of scientific data, there are no effective evidence-based forms of therapy for this condition. None of the conservative therapies have proven effective. The results of some previously published studies suggest a benefit of intravenous thrombolytic therapy in the same regimen as in the treatment of ischemic stroke. This work aims to present an overview of published clinical studies focused on the use of intravenous thrombolysis for CRAO, evaluate its efficacy and safety, and propose an optimal diagnostic and therapeutic algorithm for acute management of CRAO. Summary statistics of patient data from relevant studies indicate that a significant visual acuity improvement was achieved by a total of 45 % of patients receiving alteplase within 4.5 hours of symptoms onset. The occurrence of adverse events in this time window was not significant. Intravenous thrombolytic therapy in CRAO thus appears to be effective and safe. However, we still lack data from adequate prospective randomized controlled trials to confirm this conclusion. To date, two randomized trials are being conducted. The intravenous thrombolysis administration, patient monitoring, etiologic workup, and setting of effective secondary prevention should be ensured at the centre of highly specialized cerebrovascular care. Urgent transport of the CRAO patient to the nearest centre is essential.

Novel approaches in primary cardiovascular disease prevention: the HOPE-3 trial rationale, design, and participants' baseline characteristics

AbstractBACKGROUND:Cholesterol and blood pressure (BP) can be effectively and safely lowered with statin drugs and BP-lowering drugs, reducing major cardiovascular (CV) events by 20%-30% within 5 years in high-risk individuals. However, there are limited data in lower-risk populations. The Heart Outcomes Prevention Evaluation-3 (HOPE-3) trial is evaluating whether cholesterol lowering with a statin drug, BP lowering with low doses of 2 antihypertensive agents, and their combination safely reduce major CV events in individuals at intermediate risk who have had no previous vascular events and have average cholesterol and BP levels.METHODS:A total of 12,705 women 65 years or older and men 55 years or older with at least 1 CV risk factor, no known CV disease, and without any clear indication or contraindication to the study drugs were randomized to rosuvastatin 10 mg/d or placebo and to candesartan/hydrochlorothiazide 16/12.5 mg/d or placebo (2 × 2 factorial design) and will be followed for a mean of 5.8 years. The coprimary study outcomes are the composite of CV death, nonfatal myocardial infarction (MI), and nonfatal stroke and the composite of CV death, nonfatal MI, nonfatal stroke, resuscitated cardiac arrest, heart failure, and arterial revascularization.RESULTS:Participants were recruited from 21 countries in North America, South America, Europe, Asia, and Australia. Mean age at randomization was 66 years and 46% were women.CONCLUSIONS:The HOPE-3 trial will provide new information on cholesterol and BP lowering in intermediate-risk populations with average cholesterol and BP levels and is expected to inform approaches to primary prevention worldwide (HOPE-3 ClinicalTrials.govNCT00468923).

Pre-hospital treatment of STEMI patients. A scientific statement of the Working Group Acute Cardiac Care of the European Society of Cardiology.

In ST-elevation myocardial infarction (STEMI) the pre-hospital phase is the most critical, as the administration of the most appropriate treatment in a timely manner is instrumental for mortality reduction. STEMI systems of care based on networks of medical institutions connected by an efficient emergency medical service are pivotal. The first steps are devoted to minimize the patient's delay in seeking care, rapidly dispatch a properly staffed and equipped ambulance to make the diagnosis on scene, deliver initial drug therapy and transport the patient to the most appropriate (not necessarily the closest) cardiac facility. Primary PCI is the treatment of choice, but thrombolysis followed by coronary angiography and possibly PCI is a valid alternative, according to patient's baseline risk, time from symptoms onset and primary PCI-related delay. Paramedics and nurses have an important role in pre-hospital STEMI care and their empowerment is essential to increase the effectiveness of the system. Strong cooperation between cardiologists and emergency medicine doctors is mandatory for optimal pre-hospital STEMI care. Scientific societies have an important role in guideline implementation as well as in developing quality indicators and performance measures; health care professionals must overcome existing barriers to optimal care together with political and administrative decision makers.

[Pilot register of acute myocardial infarction--a 5-year evaluation of quality of care in non-PCI hospitals]. / Pilotní registr akutního infarktu myokardu--hodnocení kvality péce v non-PCI nemocnicích v prubehu 5 let.

INTRODUCTION: The aim of this research was to describe (demographic data and cardiovascular disease risk factors) a non-selected patient population with acute myocardial infarction and to evaluate the applied diagnostic and therapeutic approaches. PATIENTS AND METHODS: Data on 3,184 cases of acute myocardial infarction from non-PCI hospitals in Cáslav, Chrudim, Jindrichuv Hradec, Kutná Hora, Písek and Znojmo were entered in a pilot register between 2003 and 2007. RESULTS: ST elevation myocardial infarctions represented 28.5% of registered cases; primary reperfusion was indicated in 68.3% of these cases. Coronarography was indicated in 43.8% of patients in the non-ST elevation myocardial infarction subgroup. When evaluating pharmacotherapy administered during the first 24 hours following admission, a statistically significant increase in pharmacotherapy administration over the 5 years of register existence was observed (the most apparent for clopidrogel--increase from 24.6% to 63.3%). Analysis of medication recommended for use at discharge also revealed significant increase in administration of the recommended medication over the 5 years in all evaluated drug groups--the most significant, once again, for thienopyridines (increase from 34.9% to 49.6%). In-hospital mortality decreased over the 5 years from 15.2% in 2003 to 8.0% in 2007. CONCLUSION: The 5-year evaluation of diagnostic and therapeutic approaches applied in patients with acute myocardial infarction in non-PCI hospitals confirmed improvement in care provided, specifically improved adherence to pharmacotherapy as well as interventional treatment guidelines pertinent to this patient group. Together with increased quality of care, we observed a decline in in-hospital mortality of patients with acute myocardial infarction.

Rationale and design of ACTIVE: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events.

BACKGROUND: Atrial fibrillation (AF) is the most frequently occurring cardiac arrhythmia with often serious clinical consequences. Many patients have contraindications to anticoagulation, and it is often underused in clinical practice. The addition of clopidogrel to aspirin (ASA) has been shown to reduce vascular events in a number of high-risk populations. Irbesartan is an angiotensin receptor-blocking agent that reduces blood pressure and has other vascular protective effects. METHODS AND RESULTS: ACTIVE W is a noninferiority trial of clopidogrel plus ASA versus oral anticoagulation in patients with AF and at least 1 risk factor for stroke. ACTIVE A is a double-blind, placebo-controlled trial of clopidogrel in patients with AF and with at least 1 risk factor for stroke who receive ASA because they have a contraindication for oral anticoagulation or because they are unwilling to take an oral anticoagulant. ACTIVE I is a partial factorial, double-blind, placebo-controlled trial of irbesartan in patients participating in ACTIVE A or ACTIVE W. The primary outcomes of these studies are composites of vascular events. A total of 14000 patients will be enrolled in these trials. CONCLUSIONS: ACTIVE is the largest trial yet conducted in AF. Its results will lead to a new understanding of the role of combined antiplatelet therapy and the role of blood pressure lowering with an angiotensin II receptor blocker in patients with AF.

Thermal, cardiac and adrenergic responses to repeated local cooling.

The aim of this study was to ascertain whether repeated local cooling induces the same or different adaptational responses as repeated whole body cooling. Repeated cooling of the legs (immersion into 12 degrees C water up to the knees for 30 min, 20 times during 4 weeks = local cold adaptation - LCA) attenuated the initial increase in heart rate and blood pressure currently observed in control subjects immersed in cold water up to the knees. After LCA the initial skin temperature decrease tended to be lower, indicating reduced vasoconstriction. Heart rate and systolic blood pressure appeared to be generally lower during rest and during the time course of cooling in LCA humans, when compared to controls. All these changes seem to indicate attenuation of the sympathetic tone. In contrast, the sustained skin temperature in different areas of the body (finger, palm, forearm, thigh, chest) appeared to be generally lower in LCA subjects than in controls (except for temperatures on the forehead). Plasma levels of catecholamines (measured 20 and 40 min after the onset of cooling) were also not influenced by local cold adaptation. Locally cold adapted subjects, when exposed to whole body cold water immersion test, showed no change in the threshold temperature for induction of cold thermogenesis. This indicates that the hypothermic type of cold adaptation, typically occurring after systemic cold adaptation, does not appear after local cold adaptation of the intensity used. It is concluded that in humans the cold adaptation due to repeated local cooling of legs induces different physiological changes than systemic cold adaptation.

[Therapy of acute myocardial infarction in unspecialised medical centres--evaluation of diagnostic and therapeutic practice]. / Terapie akutního infarktu myokardu mimo kardiocentrum--zhodnocení diagnostických a lécebných postupu.

BACKGROUND: No general register of patients with acute coronary syndrome is available in the Czech Republic. That is why the everyday clinical practice remains indeterminate. The aim of the study was to compare patients' characteristics, diagnostic and therapeutic procedures in patients with acute myocardial infarction admitted to three municipal hospitals (Caslav, Kutna Hora, Znojmo) and to assess the correspondence of the local clinical practice with the current guidelines. METHODS AND RESULTS: A total of 564 patients (300 men, 264 women) mean age 71 +/- 11.9 years) admitted for acute myocardial infarction was included into the study. No significant difference was found in the demographic data among the hospitals. Higher proportion of smokers was observed in the hospital of Kutna Hora (p < 0.01). In the studied sample, the proportion of myocardial infarctions without ST elevation was larger than that without it (311 pts. - 73%). In the subgroup of patients with myocardial infarction and ST elevation 67% received some form of reperfusion therapy (primary angioplasty in 63 % and fibrinolytic therapy in 4%). Most patients received aspirin and heparin (78% a 82% respectively) within the first 24 hours; the treatment with beta-blockers was less common (34%). The most frequent in-hospital complication was the heart failure (23%). In-hospital mortality for all patients was 15%. At the discharge from hospital, patients received flowing treatment: aspirin (76%), beta-blockers (63%), ACE inhibitors (58%), statins (54%). A significant difference was found only in the use of clopidogrel and ticlopidin (p < 0.001). CONCLUSIONS: This study reveals only minor differences in the management of patients among hospitals and demonstrates some differences between existing guidelines and current clinical practice. The vast majority of patients with acute myocardial infarction with ST elevation was treated by primary angioplasty.

Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial.

BACKGROUND: Bolus fibrinolytic therapy facilitates early efficient institution of reperfusion therapy. Tenecteplase is a genetically engineered variant of alteplase with slower plasma clearance, better fibrin specificity, and high resistance to plasminogen-activator inhibitor-1. We did a double-blind, randomised, controlled trial to assess the efficacy and safety of tenecteplase compared with alteplase. METHODS: In 1021 hospitals, we randomly assigned 16,949 patients with acute myocardial infarction of less than 6 h duration rapid infusion of alteplase (< or = 100 mg) or single-bolus injection of tenecteplase (30-50 mg according to bodyweight). All patients received aspirin and heparin (target activated partial thromboplastin time 50-75 s). The primary outcome was equivalence in all-cause mortality at 30 days. FINDINGS: Covariate-adjusted 30-day mortality rates were almost identical for the two groups--6.18% for tenecteplase and 6.15% for alteplase. The 95% one-sided upper boundaries of the absolute and relative differences in 30-day mortality were 0.61% and 10.00%, respectively, which met the prespecified criteria of equivalence (1% absolute or 14% relative difference in 30-day mortality, whichever difference proved smaller). Rates of intracranial haemorrhage were similar (0.93% for tenecteplase and 0.94% for alteplase), but fewer non-cerebral bleeding complications (26.43 vs 28.95%, p=0.0003) and less need for blood transfusion (4.25 vs 5.49%, p=0.0002) were seen with tenecteplase. The rate of death or non-fatal stroke at 30 days was 7.11% with tenecteplase and 7.04% with alteplase (relative risk 1.01 [95% CI 0.91-1.13]). INTERPRETATION: Tenecteplase and alteplase were equivalent for 30-day mortality. The ease of administration of tenecteplase may facilitate more rapid treatment in and out of hospital.

[How knowledgeable are Czech physicians regarding risk factors for ischemic heart disease?]. / Jaké jsou znalosti nasich lékaru o rizikových faktorech ischemické choroby srdecní?

The authors present the results of an enquiry made by means of questionnaires in which 298 physicians participated. The enquiry was focused on risk factors of ischaemic heart disease. 41.8% physicians did not know their cholesterol level, 22.1% admitted that they smoked and another 17.8% were ex-smokers. Only half the physicians indicate dietetic treatment of hypercholesterolaemia when the blood level is 6.2 mmol/l. These and other data in the paper indicate that behaviour and knowledge of physicians as regards prevention of cardiovascular diseases most be substantially improved.

Effect of isradipine on 24-h blood pressure profile demonstrated by repeated monitoring.

The antihypertensive effect of isradipine was assessed by repeated 24-h ambulatory blood pressure monitoring. Using an SPS device (Sandoz Pharma, Basel, Switzerland), monitoring was carried out in 10 male patients with mild essential hypertension (1) after a placebo period, (2) after six months, and (3) after 12 to 13 months of treatment with isradipine (average dose 2.5 mg twice daily). Mean 24-h blood pressure decreased significantly after both periods 2 and 3 (from 148/93 mm Hg to 137/87 and 130/85 mm Hg, respectively). The total number of hypertensive systolic and diastolic blood pressure values also decreased. The normal circadian blood pressure curve was preserved, showing the reduction throughout the 24-h period, and the early morning rise in blood pressure was markedly blunted. These results indicate that isradipine has a favorable effect on the 24-h blood pressure profile that persisted throughout six and 12 months of antihypertensive therapy.

24-hour ambulatory blood pressure monitoring in the treatment of mild hypertension with isradipine.

Twenty-four-hour ambulatory blood pressure (BP) monitoring allows the physician to follow the course of blood pressure of a patient at the worksite, at home, and during sleep. All these undisputed advantages made the technique an important part of studies designed to assess the effect of new antihypertensive drugs. In a study involving 14 patients with mild hypertension. 24-hour BP levels were monitored before and after treatment with isradipine (Lomir, Sandoz), a new calcium antagonist. A marked decrease in mean systolic BP (146.8 +/- 4.1 vs. 133.8 +/- 3.3 mmHg, p less than 0.01) as well as diastolic pressure (92.4 +/- 1.4 vs. 86.0 +/- 1.1 mmHg, p less than 0.01) was found after 6-month therapy compared with the values determined in the placebo period. The incidence of hypertensive BP values during the day was likewise reduced. The circadian rhythm of BP was retained. The nocturnal decrease in BP was less prominent than during the day, and there was a marked reduction in the rapid morning rise in BP. Overall, 24-hour BP monitoring demonstrated a favourable effect of isradipine on the diurnal profile of BP.