Carotid plaque characterisation by IVUS-VH during carotid stenting: the "eyes wide shut" between plaque morphology and symptoms.

Stroke is the third most common cause of death in North America and ever year approximately 700,000 new strokes are reported in the United States. Seventy-five percent of these occur in the distribution of the carotid arteries. Among strokes of a thromboembolic etiology, carotid occlusive disease is the most common cause. As many as 150,300 stroke-related fatalities are documented annually, with a total cost for the health-care system of approximately $ 18 billion per year. This review will focus on the different pathomorphologic aspects of carotid plaque, outlining the similarities and differences with the coronary plaque, with particular attention on how intravascular imaging may contribute to a better stratification of the patient treatment.

Coronary artery disease: clinical presentation, diagnosis and prognosis in women.

Recent advances in the field of cardiovascular medicine have not led to significant declines in case-fatality rates for women as in men. There are gender-specific differences in symptoms profile, diagnosis and treatment of coronary disease in women. For women presenting for coronary heart disease (CHD) evaluation, traditional disease management approaches that focus on detection of a 'critical stenosis' often fail to identify those women critically at-risk. Symptoms do not help physicians in differential diagnosis of chest pain in women; indeed the most common presentation of obstructive CHD in women is atypical symptoms. In 50% of the cases, non-obstructive CHD at coronary angiography, due to 'noncardiac chest pain' or coronary microvascular dysfunction is frequently reported. For these reasons, the evidence reviewed suggests that prognostic risk assessment may work relatively better than diagnostic obstructive coronary disease assessment for women.

Perioperative red blood cell transfusion and outcome in stable patients after elective major vascular surgery.

OBJECTIVES: Definitive evidence that red blood cell transfusion improves outcome after vascular surgery is lacking. The aims of the study were to determine, among stable consecutive patients who underwent elective major vascular surgery, (1) the association between postoperative transfusion and 30-day death, myocardial infarction, and both, and (2) and if this association differs according to the presence of postoperative anaemia (haemoglobin value less than 9.0 g/dL within 7 days after surgery). METHODS: A retrospective observational study was conducted on 359 patients prospectively screened according to the ACC/AHA guidelines for preoperative risk in non-cardiac surgery. Main outcome was 30-day death; secondary outcomes 30-day myocardial infarction, and composite of 30-day myocardial infarction or death. RESULTS: Of the patients included, 95 (26.5%) received at least one unit of red blood cells. Patients who received transfusion had a significantly increased hazard of 30-day death (hazard ratio [HR] 11.72, 95% confidence interval [CI] 3.92-35.10; p<0.0001), myocardial infarction (HR 3.3, 95% CI 1.7-6.1; p=0.0003), and both (HR 4.0 95% CI 2.2-7.3; p<0.0001). Such associations held even after adjusting for baseline characteristics, surgical risk, bleeding, and propensity to receive transfusion. There was a significant interaction between transfusion and postoperative anaemia (p=0.012). In patients without anaemia, transfusion was associated with higher risk of 30-day death (HR 19.20, 95% CI 3.99-92.45; p=0.007), myocardial infarction (HR 5.05, 95% CI 2.23-11.44; p=0.0001), and both. Conversely, in patients with anaemia this association was not significant. CONCLUSIONS: In patients who underwent elective major vascular surgery, perioperative transfusion was associated with a significantly increased risk of 30-day events which was more attributable to patients with lesser degree of anaemia. Our data caution against the use of liberal transfusion in stable vascular surgery patients.

The management of pre-hypertension and metabolic syndrome.

The new guidelines for diagnosis and treatment of arterial hypertension introduce the new concept of "pre-hypertension", that comprises those individuals who have either systolic blood pressure (BP) of 120-139 mmHg or diastolic BP of 80-89 mmHg. The Committee recommended the identification of these individuals as they are at increased risk for progression to hypertension and subsequently other cardiovascular disease (CVD). Metabolic syndrome (MS) is a constellation of CVD risk factors, including atherogenic dyslipidemia, elevated BP, impaired glucose regulation, and abdominal obesity. Compared to those without MS, individuals with MS have a 61% increased risk of CVD. The aim of the review was explain the "real" relationship between these two clinical conditions describing the pathogenic mechanisms that put them in correlation. These findings may also offer compelling evidence for screening and early detection in vulnerable groups predisposed to CVD. Randomized intervention studies are needed to quantify the extent of any potential benefit of therapy among individuals with BP levels usually considered normal.

Paclitaxel eluting balloon: from bench to bedside.

Despite the impressive progress of percutaneous treatment modalities, restenosis remains the major Achilles heel of interventional cardiology. Approximately 25% of the general population treated for coronary diseases with a bare-metal stent and about 10% of patients treated with a drug-eluting stent develop an overgrowth of vascular tissue and renarrowing inside the stent, or in-stent restenosis. These rates are even greater in diabetics and patients at higher risk of restenosis both for clinical presentation (patients in dialysis, low ejection fraction) or anatomical characteristics (ostial, bifurcation, long lesions). Non-stent based local drug delivery and particularly the use of paclitaxel eluting balloon (PEB) could be one promising strategy to reduce restenosis. This review will briefly explore the different characteristics of PEB devices currently present in the market and summarize the results obtained both in animal models and clinical practice, giving an indication of the potential field of application of this new technology.

Cardiovascular risk and prostanoids in systemic sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) is characterized by Raynaud's phenomenon and frequent cutaneous ulcers. In patients resistant to oral treatments, i.v. prostanoids are usefully employed. Some anecdotal reports underlined the potential risk to develop cardiovascular ischemic complications in prostanoid-treated SSc patients. METHODS: Fifty SSc patients (group 1: 44 female and 6 male, mean age 60.4 +/- 13.8SD) undergoing long-term prostanoid therapy (iloprost or alprostadil) and 42 control patients (group 2), treated with only oral drugs, were retrospectively evaluated for the cardiovascular risk and incidence of ischemic events. RESULTS: Ischemic cardiovascular complications, i.e., myocardial infarction or stroke, were recorded in a significantly higher number of patients undergoing prostanoid treatment compared to controls (group 1: 7/50, 14% vs. group 2: 1/42, 2.4%; p=0.041). Interestingly, these events were significantly more frequent in the subgroup of patients with high cardiovascular risk (group 1: 6/10, 60% vs. group 2: 1/19, 5.2%; p=0.0026). CONCLUSION: The present study suggests a possible role of prostanoid treatment in the pathogenesis of ischemic cardiovascular complications in SSc patients non-responders to oral vasodilators and high cardiovascular risk. Since prostanoids represent the first choice treatment of the most severe scleroderma ischemic cutaneous lesions, cardiovascular risk should be carefully evaluated in all patients before therapy.

Anti- and pro-oxidant factors and endothelial dysfunction in chronic cigarette smokers with coronary heart disease.

BACKGROUND: Endothelial dysfunction in cigarette smokers has been ascribed to increased oxidative damage. The aims of the present study were to compare the endothelial function of normotensive smokers with that of non-smokers and to examine its relation to some parameters representative of oxidative damage and of antioxidant capacity. METHODS: We investigated 32 chronic smokers (15-30 cigarettes daily) affected by coronary heart disease, ranging from acute myocardial infarction to instable angina pectoris, and 28 matched non-smokers without any definite risk factors. All subjects underwent assessment of nitric oxide (NO)-dependent endothelial function, measured as brachial artery vasodilatation in response to reactive ischemia, using a standardized echographic method. Plasma and urinary levels of NO were also measured in all subjects, as were urinary 15-isoprostane F(2t), plasma serum lipids, homocysteine (Hcy), ascorbic acid, retinol, tocopherol, and alpha- and beta-carotene (by high-performance liquid chromatography). RESULTS: Smokers showed a significantly lower NO-mediated vasodilatation response (3.50% vs. 6.18%, p<0.001) and higher levels of urinary NO metabolites and 15-isoprostane F(2t). They also had higher levels of Hcy (p<0.001); these values were significantly and inversely related to NO serum levels (r=-0.512, p<0.001). Moreover, smokers had a significant and corresponding reduction in circulating levels of ascorbic acid, tocopherol, and alpha- and beta-carotene. CONCLUSIONS: The present study shows a clear relation between endothelial dysfunction (NO production impairment) and cigarette smoking, especially in the presence of high levels of LDL-cholesterol. It also defines some markers of both oxidative damage and antioxidant protective capacity in this condition. The monitoring of these factors may be advisable in order to assess the amount of endothelial damage.

Coronary calcification in cardiovascular risk stratification.

The correlation between coronary calcifications and subclinical atherosclerotic disease has been well known for some years now. Today we are able to quantify coronary calcium deposits, the calcium score, by means of new imaging techniques such as electron beam computed tomography and multislice spiral computed tomography. A large number of studies performed using these methods has confirmed the association between coronary calcifications and atherosclerotic disease and has opened up the possibility of early diagnosis of any subclinical atherosclerotic disease in various subpopulations such as diabetics and nephropatics. The etiopathogenesis of coronary calcium has not yet been made clear; it appears to be an active process similar to bone formation that involves cells similar to those involved in the reabsorption of bone matrix. The calcium score, therefore, provides physicians with a further diagnostic tool able to better determine cardiovascular risk patients and supplements the Framingham risk score. International guidelines have not yet illustrated with any precision in which ambits to apply screening for the quantification of coronary calcium and consequently, for the time being, the use of such methods must be restricted to cases in which the possibility of any benefit can be scientifically shown. This review represents the state of the art on coronary calcification and its role in clinical practice.

Differential effects of beta-blockers in patients with heart failure: A prospective, randomized, double-blind comparison of the long-term effects of metoprolol versus carvedilol.

BACKGROUND: Both metoprolol and carvedilol produce hemodynamic and clinical benefits in patients with chronic heart failure; carvedilol exerts greater antiadrenergic effects than metoprolol, but it is unknown whether this pharmacological difference results in hemodynamic and clinical differences between the 2 drugs. METHODS AND RESULTS: We randomized 150 patients with heart failure (left ventricular ejection fraction

Effect of prolonged administration of transdermal estradiol on flow-mediated endothelium-dependent and endothelium-independent vasodilation in healthy postmenopausal women.

In 15 postmenopausal women with no cardiovascular risk factors, hormone replacement with transdermal estradiol (50 microg/day for 2 months) did not enhance flow-mediated endothelium-dependent vasodilation, reduce endothelium-independent vasodilation, and did not modify the pulsatility index and blood flow of the brachial artery. The present data do not support a positive effect of replacement with transdermal estradiol on vessel vasodilation in healthy, postmenopausal women.

Short atrioventricular delay reduces the degree of mitral regurgitation in patients with a sequential dual-chamber pacemaker.

This study was performed in a population of sequential dual-chamber pacemaker-patients with isolated mitral regurgitation (MR) to identify the "ideal atrioventricular (AV) delay" and to determine the effect of sequential pacing with the ideal AV delay on MR degree. Twenty consecutive patients (age 69 +/- 7 years; 45% men) hospitalized at our institution for symptomatic III degree AV block and isolated MR were studied. All received a dual-chamber pacemaker programmed in DDD at a rate of 70 pulses/minute. The ideal AV delay was selected using echo-color Doppler parameters; it was defined as that resulting in a lower degree of MR and in the highest cardiac output. The mean "optimal short" AV delay resulted in 98 +/- 7 ms. At short AV delay we observed a significant reduction in MR severity (regurgitant fraction from 48 +/- 12% to 25 +/- 10% and jet area from 15 +/- 2 to 9 +/- 2 cm2; p <0.0001) together with an increase in stroke volume (68 +/- 16 vs 88 +/- 15 ml; p = 0.007) and mitral early-to-late peak velocity ratio (0.79 +/- 0.33 vs 1.38 +/- 0.37; p <0.0001). In conclusion, a short AV delay may be used to improve cardiac output in sequential paced patients with pure, isolated MR.

Right ventricular pacing and left ventricular filling pattern. An echo-Doppler study.

The influence of right ventricular pacing on left ventricular filling has not been completely clarified. The aim of the study was to analyze the possible alteration in and effects on left ventricular filling resulting from right ventricular pacing. The study population consisted of two groups; group A was comprised of 12 patients with a spontaneous left bundle branch block, and group B had 12 patients without left bundle branch block. All the patients underwent an interrogation of the mitral valve inflow by Doppler echocardiography, in order to measure isovolumic relaxation time, early and late peak velocity (E and A wave), E/A ratio and deceleration time. The study was performed at spontaneous rhythm and after, inhibition of the pacemaker. In group A, there were no changes in the Doppler parameters when passing from a spontaneous to an 80/min electrically induced rhythm. Analysis of group B revealed a statistically significant lengthening of IVR and Dec t with electrical stimulation. No statistically significant differences were found when we compared the Doppler parameters of the two populations at the same pacing frequency. Right ventricular pacing causes interventricular asynchrony and abnormalities in diastolic filling times, which resulted in a lengthening of either IVR and Dec t, simulating a pattern of abnormal relaxation.

Double-blind randomized placebo-controlled study of transdermal estrogen replacement therapy on hypertensive postmenopausal women.

We investigated the effects of transdermal 17beta-estradiol, combined with standard antihypertensive therapy, on the modification of the cardiovascular risk profile in hypertensive postmenopausal women. In a randomized, double-blind, placebo-controlled study, we enrolled 200 postmenopausal women with mild to moderate hypertension. Patients received 17beta-estradiol (50 microg/day, transdermal) and norethisterone acetate (2.5 mg/ day, orally) or placebo. At baseline serum total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, glucose, and fibrinogen plasma levels were measured and all subjects underwent complete M-mode and 2-D echocardiograms, which were repeated after 6, 12, and 18 months of hormonal replacement therapy. Compared with placebo, all values decreased significantly except for HDL cholesterol. In both groups, no modifications were observed in echocardiographic parameters, except for left ventricular mean diastolic and systolic wall thickness and left ventricular mass index, which showed a significant decrease in both groups. The reduction was greater in the treated group; the percentage of patients with left ventricular hypertrophy was 46% before randomization and 17.2% after 18 months of treatment (P < .0001), whereas in group II the percentage was 48% at baseline and 31.5% after 18 months (P < .05). In conclusion, transdermal 17beta-estradiol, associated with antihypertensive therapy, may contribute to the reduction of cardiovascular risk profile in hypertensive postmenopausal women.

Relationship between atrial function, left ventricular isovolumic relation time, and early filling in dual chamber-paced patients.

This investigation was performed to study atrial systolic function is response to modification of atrioventricular delay in a sample of 36 patients with a DDD pacemaker implanted for complete atrioventricular block. The relation between atrial systolic performance and diastolic-related parameters was also evaluated. Isovolumic relaxation time, early diastolic peak velocity, late (atrial) diastolic peak velocity, atrial filing fraction, and atrial ejection force were recorded at a pacing rate of 70 impulses/min and at atrioventricular delay of 200, 150, and 100 msec. Our data showed that the progressive shortening of atrioventricular delay induced a gradual increase in early peak velocity (median value 46 to 53 to 61.5 cm/sec, respectively, at 200, 150, and 100 msec intervals) and a gradual decrease in isovolumic relaxation time (median 92.6 to 81.5 to 69.7 msec at 200, 150, and 100 msec, respectively), atrial peak velocity (59 to 52 to 44.5 cm/sec at 200, 150, and 100 msec, respectively), atrial filling fraction (50.5% to 40% to 23.5% at 200, 150, and 100 msec, respectively), and atrial ejection force (17.2 to 14.7 to 8.5 kilodynes at 200, 150, and 100 msec, respectively). For every atrioventricular delay value detected, we found a significant correlation between isovolumic relaxation time and early peak velocity with atrial filling fraction and atrial ejection force. In addition, atrial ejection force was related directly to atrial filling fraction at studied atrioventricular delays. The two indexes of atrial systolic performance showed a parallel decrease by shortening the atrioventricular delay, and they can quantify atrial systolic performance equally in sequentially paced patients. Furthermore, our results are in accordance with the hypothesis that the interaction between the effectiveness of active left atrial emptying and isovolumetric relaxation time may play an important role in maintaining an ideal ventricular filling despite changes in atrial systolic function.

Echocardiographic evaluation of cardiovascular effects of amrinone.

Amrinone, a new inotropic drug, was infused at a dosage of 2.5 mg/kg body weight in 14 patients affected by dilatative cardiomyopathy in New York Heart Association (NYHA) functional class III and IV. Cardiac index, mean arterial pressure, and some echocardiographic parameters were evaluated. Cardiac index (CI) increased from 2.03 +/- 0.24 to 2.82 +/- 0.43 1/min/m2 (p less than 0.001). Fractional shortening (FS) increased from 16.4 +/- 5.2 to 21.5 +/- 5.3% (p less than 0.05). End-diastolic and end-systolic diameters showed a significant reduction. Mean arterial pressure decreased from 90.7 +/- 88 to 87.3 +/- 8.4 mmHg (p less than 0.001), the end-systolic stress (ESS) decreased from 5.8 +/- 1 to 5.2 +/- 1 g/cm (p less than 0.001). Analyzing the relationship between FS and ESS, it was possible in some cases to suppose the presence of an important vasodilator effect of the drug. The afterload in 7 patients was therefore modified before and after infusion of the drug to analyze FS at the same levels of afterload. This was done to evaluate the vasodilator effect of amrinone. Examining the regression line of FS/ESS ratio it was possible to observe a predominant vasodilator effect in some patients, but in most, a sinergic action was noted. This may be useful for chronic treatment of congestive heart failure, reducing amrinone doses, and using it in association with other vasodilator drugs.

Echocardiographic monitoring of mental stress test in ischemic heart disease.

Mental stress testing can induce ischemia in coronary patients, but often may not induce chest pain and/or electrocardiographic changes. Therefore, we tested the utility of echocardiography to increase the sensitivity of the method. For this purpose, 56 patients undertook arithmetic mental stress tests and then were subjected to coronary angiography. During the test we evaluated left ventricular function, electrocardiography results, and emotional involvement measured by STAI (State Trait Anxiety Inventory). Echocardiography was positive in 21 patients, and electrocardiogram only in 2 patients. No patient complained of chest pain. The remaining 35 patients were negative. Comparing echo data with coronary angiography, in all the cases, sensitivity was 73.5%, specificity 93.3%. Analysis of the STAI revealed that the negative test we observed could be due to a low stressor efficacy. In conclusion, echocardiography in mental stress testing permits improved sensitivity, with loss of specificity in comparison with conventional electrocardiographic monitoring.

Left atrial size is the major predictor of cardiac death and overall clinical outcome in patients with dilated cardiomyopathy: a long-term follow-up study.

HYPOTHESIS: This study was undertaken to determine whether echo-derived left atrial dimension and other echocardiographic, clinical, and hemodynamic parameters detected at the time of entry into the study may influence prognosis in patients with dilated cardiomyopathy during a long-term follow-up. METHODS: This was a prospective cohort analysis of 123 patients with dilated cardiomyopathy. Clinical evaluation, chest x-ray, M-mode and two-dimensional echocardiogram, exercise test, 72-h ambulatory electrocardiogram monitoring, and cardiac catheterization study were performed in all patients. The study was divided into two phases: in the first phase, patients were divided into two groups according to the left atrial size (> or = 45 mm; < 45 mm), with cardiac death as the end point. In the second phase, all patients were further divided into two groups according to their clinical course. A multivariate analysis was performed to determine independent correlated parameters of cardiac mortality and overall clinical outcome. RESULTS: Cardiac mortality rate was 47.9%: 29% in the group without left atrial dilation and 54.3% in the group with dilated left atrium. Multivariate analysis revealed that left atrium > or = 45 mm, New York Heart Association functional classes III/IV, and the presence of one or more episodes of ventricular tachycardia at Holter monitoring were independent predictors of cardiac mortality, while left atrium > or = 45 mm, left ventricular end-diastolic pressure > 17 mmHg, and exercise tolerance < or = 15 min were independent predictors of poor clinical outcome. CONCLUSIONS: Our results revealed that left atrial size is the principal independent predictor of prognosis in patients with dilated cardiomyopathy in that patients with left atrial dilation had an increase in mortality and a worse clinical outcome compared with those without left atrial dilation.

Early predictors of late dilation and remodeling after thrombolized anterior transmural myocardial infarction.

BACKGROUND AND HYPOTHESIS: Dilation of the left ventricle after myocardial infarction is associated with an adverse prognosis. There are no clinical studies on the role viable myocardium in the infarcted area assumes in relation to the development of late ventricular remodeling. The hypothesis of this study was to define the relation between remodeling and the presence of viable but akinetic myocardium in the infarct area and to identify early predictors of left ventricular (LV) dilation at 1 year. METHODS: In all, 92 consecutive patients with myocardial infarction were divided into two groups according to their ventricular volumes. Group I included 57 patients with normal volumes at discharge (9 +/- 3 days after acute infarction) and after 12 months or with LV dilation at discharge who had a normalization of their volumes over a 12-month period. Group II included 35 patients who, independent of their initial volumes, developed LV dilation during follow-up. Low-dose dobutamine infusion was utilized at discharge for echocardiographic evaluation of contractile recovery of viable myocardial segments. RESULTS: At the first control, patients in Group I presented an end-diastolic volume index (EDVI) of 100 +/- 7 ml/m2 which decreased to 68.8 +/- 6.5 ml/m2 12 months later (p < 0.0001), and an end-systolic volume index (ESVI) of 47.6 +/- 6.7 ml/m2 at the first control and 30.5 +/- 8.8 ml/m2 after 12 months (p < 0.001). Patients in Group II presented a mean EDVI of 116.2 +/- 8.1 ml/m2 at the first control and 138.8 +/- 8 ml/m2 12 months later (p < 0.001), and a mean ESVI of 68.8 +/- 6.5 ml/m2 at the first control and 79.5 +/- 5.4 after 12 months (p < 0.01). Ventricular mass index (VMI) in Group I increased from 106.4 +/- 11 to 122.3 +/- 15 g/m2 (p < 0.01), while in Group II it decreased from 101.1 +/- 10 to 98.7 +/- 8 g/m2 (p = NS). In Group I, mass-to-volume ratio was 1.15 +/- 0.1 g/ml at the first control and 1.67 +/- 0.1 g/ml 12 months later (p < 0.001), while in Group II it declined from 0.88 +/- 0.1 to 0.69 +/- 0.1 g/ml (p < 0.01). The multivariate analysis revealed that ejection fraction < or = 40%, restrictive filling pattern, wall motion score index > 2.5 in response to dobutamine infusion, and mass-to-volume ratio < or = 1 g/ml, all at discharge, as well as an occluded left anterior descending artery discriminate in favor of late LV dilation and remodeling. CONCLUSIONS: Correct use of noninvasive strategies should result in early identification of postinfarct patients who are at risk of developing LV remodeling.

[The diagnosis of ischemic cardiopathy in women]. / La diagnosi di cardiopatia ischemica nella donna.

Risk stratification and therefore evaluation of pre-test probability of coronary artery disease represent an important point in order to choose the ideal noninvasive test in women. Risk evaluation may be performed in relation to the presence of so-called major (hypertension, diabetes, age > 65 years) or minor (dyslipidemia, smoking abuse) risk factors. The standard ECG exercise test represents an important step, but only if easily interpretable and feasible: a complete negative test suggest the absence of coronary artery disease; its positivity should indicate the opportunity to perform coronary angiography in the presence of moderate to severe pre-test probability. If ECG exercise test is not feasible, we would suggest a test of imaging; in the case of high pre-test probability we would recommend a test with high specificity, such as echo-stress test, whereas in the case of lower pre-test probability we would prefer a test with high sensitivity, such as myocardial scintigraphy.

Comparative effectiveness of novel oral anticoagulants for atrial fibrillation: evidence from pair-wise and warfarin-controlled network meta-analyses.

INTRODUCTION: Novel oral anticoagulants have been tested against warfarin for atrial fibrillation, yet no direct comparison is available. We thus aimed to perform pair-wise (direct) and warfarin-adjusted network (i.e. indirect) meta-analyses of novel oral anticoagulants for atrial fibrillation. METHODS: Databases were searched for randomized warfarin-controlled trials of novel anticoagulants for non-valvular atrial fibrillation. The primary end-point was long-term stroke/systemic embolism. Odds ratios (95% intervals) were computed with RevMan and WinBUGS. RESULTS: Seven trials (52701 patients) were included, focusing on apixaban, dabigatran, edoxaban and rivaroxaban. Pair-wise meta-analysis showed that after a weighted average of 23 months these novel anticoagulants lead to significant reductions in the risk of stroke/systemic embolism (odds ratio=0.81 [0.71-0.92], I2=23%) and all cause death (odds ratio=0.88 [0.82-0.95], I2=0%) in comparison to warfarin. Network meta-analysis showed that apixaban and dabigatran proved similarly superior to warfarin in preventing stroke/systemic embolism (odds ratio=0.78 [0.62-0.96] for apixaban vs warfarin; odds ratio=0.66 [0.52-0.84] for high-dose dabigatran vs warfarin; odds ratio for apixaban vs high-dose dabigatran=1.17 [0.85-1.63]), but apixaban was associated with fewer major bleedings (odds ratio=0.73 [0.57-0.93]) and drug discontinuations (odds ratio=0.64 [0.52-0.78]) than dabigatran. Rivaroxaban did not reduce stroke/systemic embolism (odds ratio=0.87 [0.71-1.07]) or major bleedings in comparison to warfarin (odds ratio=0.87 [0.71-1.07]) and was associated with more major bleedings in comparison to apixaban (odds ratio=1.52 [1.19-1.92]). Data for edoxaban were inconclusive. CONCLUSIONS: Novel oral anticoagulants appear as a very promising treatment option for atrial fibrillation.