Effect of Systemic Hypertension With Versus Without Left Ventricular Hypertrophy on the Progression of Atrial Fibrillation (from the Euro Heart Survey).

Hypertension is a risk factor for both progression of atrial fibrillation (AF) and development of AF-related complications, that is major adverse cardiac and cerebrovascular events (MACCE). It is unknown whether left ventricular hypertrophy (LVH) as a consequence of hypertension is also a risk factor for both these end points. We aimed to assess this in low-risk AF patients, also assessing gender-related differences. We included 799 patients from the Euro Heart Survey with nonvalvular AF and a baseline echocardiogram. Patients with and without hypertension were included. End points after 1 year were occurrence of AF progression, that is paroxysmal AF becoming persistent and/or permanent AF, and MACCE. Echocardiographic LVH was present in 33% of 379 hypertensive patients. AF progression after 1 year occurred in 10.2% of 373 patients with rhythm follow-up. In hypertensive patients with LVH, AF progression occurred more frequently as compared with hypertensive patients without LVH (23.3% vs 8.8%, p = 0.011). In hypertensive AF patients, LVH was the most important multivariably adjusted determinant of AF progression on multivariable logistic regression (odds ratio 4.84, 95% confidence interval 1.70 to 13.78, p = 0.003). This effect was only seen in male patients (27.5% vs 5.8%, p = 0.002), while in female hypertensive patients, no differences were found in AF progression rates regarding the presence or absence of LVH (15.2% vs 15.0%, p = 0.999). No differences were seen in MACCE for hypertensive patients with and without LVH. In conclusion, in men with hypertension, LVH is associated with AF progression. This association seems to be absent in hypertensive women

Progression From Paroxysmal to Persistent Atrial Fibrillation. Clinical Correlates and Prognosis

Objectives: We investigated clinical correlates of atrial fibrillation (AF) progression and evaluated the prognosis of patients demonstrating AF progression in a large population. Background: Progression of paroxysmal AF to more sustained forms is frequently seen. However, not all patients will progress to persistent AF. Methods: We included 1,219 patients with paroxysmal AF who participated in the Euro Heart Survey on AF and had a known rhythm status at follow-up. Patients who experienced AF progression after 1 year of follow-up were identified. Results: Progression of AF occurred in 178 (15%) patients. Multivariate analysis showed that heart failure, age, previous transient ischemic attack or stroke, chronic obstructive pulmonary disease, and hypertension were the only independent predictors of AF progression. Using the regression coefficient as a benchmark, we calculated the HATCH score. Nearly 50% of the patients with a HATCH score >5 progressed to persistent AF compared with only 6% of the patients with a HATCH score of 0. During follow-up, patients with AF progression were more often admitted to the hospital and had more major adverse cardiovascular events. Conclusions: A substantial number of patients progress to sustained AF within 1 year. The clinical outcome of these patients regarding hospital admissions and major adverse cardiovascular events was worse compared with patients demonstrating no AF progression. Factors known to cause atrial structural remodeling (age and underlying heart disease) were independent predictors of AF progression. The HATCH score may help to identify patients who are likely to progress to sustained forms of AF in the near future. \ua9 2010 American College of Cardiology Foundation

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects.

BACKGROUND: The long-term effects of sibutramine treatment on the rates of cardiovascular events and cardiovascular death among subjects at high cardiovascular risk have not been established. METHODS: We enrolled in our study 10,744 overweight or obese subjects, 55 years of age or older, with preexisting cardiovascular disease, type 2 diabetes mellitus, or both to assess the cardiovascular consequences of weight management with and without sibutramine in subjects at high risk for cardiovascular events. All the subjects received sibutramine in addition to participating in a weight-management program during a 6-week, single-blind, lead-in period, after which 9804 subjects underwent random assignment in a double-blind fashion to sibutramine (4906 subjects) or placebo (4898 subjects). The primary end point was the time from randomization to the first occurrence of a primary outcome event (nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death). RESULTS: The mean duration of treatment was 3.4 years. The mean weight loss during the lead-in period was 2.6 kg; after randomization, the subjects in the sibutramine group achieved and maintained further weight reduction (mean, 1.7 kg). The mean blood pressure decreased in both groups, with greater reductions in the placebo group than in the sibutramine group (mean difference, 1.2/1.4 mm Hg). The risk of a primary outcome event was 11.4% in the sibutramine group as compared with 10.0% in the placebo group (hazard ratio, 1.16; 95% confidence interval [CI], 1.03 to 1.31; P=0.02). The rates of nonfatal myocardial infarction and nonfatal stroke were 4.1% and 2.6% in the sibutramine group and 3.2% and 1.9% in the placebo group, respectively (hazard ratio for nonfatal myocardial infarction, 1.28; 95% CI, 1.04 to 1.57; P=0.02; hazard ratio for nonfatal stroke, 1.36; 95% CI, 1.04 to 1.77; P=0.03). The rates of cardiovascular death and death from any cause were not increased. CONCLUSIONS: Subjects with preexisting cardiovascular conditions who were receiving long-term sibutramine treatment had an increased risk of nonfatal myocardial infarction and nonfatal stroke but not of cardiovascular death or death from any cause. (Funded by Abbott; ClinicalTrials.gov number, NCT00234832.

Prognosis, disease progression, and treatment of atrial fibrillation patients during 1 year: Follow-up of the Euro Heart Survey on Atrial Fibrillation

Aims: To gain insight in the prognosis and treatment of atrial fibrillation (AF) patients during 1-year follow-up in the Euro Heart Survey (EHS) on AF. Methods and results: The EHS enrolled 5333 AF patients in 2003-2004. One-year follow-up data were available for 80%. Of first detected AF patients, 46% did not have a recurrence during 1 year, paroxysmal AF largely remained paroxysmal AF (80%), and 30% of persistent AF progressed to permanent AF. Many treatment changes occurred since baseline. Oral anticoagulation was started in 19% and discontinued in 16% of all patients. Of patients initially on rhythm control 27% did not receive rhythm control during follow-up, whereas 15% of patients initially on rate control received rhythm control. Mortality was highest in permanent AF (8.2%), but also substantial in first detected AF (5.7%). In multivariable analysis, sinus rhythm at baseline was associated with lower mortality, but no significant effect was observed regarding the application of either rhythm or rate control. Conclusion: The EHS on AF provides unique prospective observational data on AF progression, long-term treatment, prognosis, and determinants of adverse outcome of the total clinical spectrum of AF in a European cardiology-based patient cohort. © The Author 2008

Gender-related differences in presentation, treatment, and outcome of patients with atrial fibrillation in Europe - A report from the Euro Heart Survey on atrial fibrillation

Objectives This study sought to investigate gender-related differences in patients with atrial fibrillation (AF) in Europe. Background Gender-related differences may play a significant role in AF. Methods We analyzed the data of 5,333 patients (42% female) enrolled in the Euro Heart Survey on Atrial Fibrillation. Results Compared with men, the women were older, had a lower quality of life (QoL), had more comorbidities, more often had heart failure (HF) with preserved left ventricular systolic function (18% vs. 7%, p &lt; 0.001), and less often had HF with systolic dysfunction (17% vs. 26%, p &lt; 0.001). Among patients with typical AF symptoms (56% of women, 49% of men), there was no gender-related difference in the choice of rate or rhythm control. Among patients with atypical or no symptoms (44% of women, 51% of men), women less frequently underwent rhythm control (39% vs. 51%, p &lt; 0.001) than did men. Women underwent less electrical cardioversion (22% vs. 28%, p &lt; 0.001). Prescription of oral anticoagulants was identical (65%) in both genders. One-year outcome was similar except that women had a higher chance for stroke (odds ratio 1.83 in multivariable regression analysis, p = 0.019). Conclusions Women with AF had more comorbidities, more HF with preserved systolic function, and a lower QoL than men. In the large group with atypical or no symptoms, women were treated appropriately more conservatively with less rhythm control than men. Women had a higher chance for stroke. Long-term QoL changes and other morbidities and mortality were similar

A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: The euro heart survey

Objective: Despite extensive use of oral anticoagulation (OAC) in patients with atrial fibrillation (AF) and the increased bleeding risk associated with such OAC use, no handy quantification tool for assessing this risk exists. We aimed to develop a practical risk score to estimate the 1-year risk for major bleeding (intracranial, hospitalization, hemoglobin decrease &gt;2 g/L, and/or transfusion) in a cohort of real-world patients with AF. Methods: Based on 3,978 patients in the Euro Heart Survey on AF with complete follow-up, all univariate bleeding risk factors in this cohort were used in a multivariate analysis along with historical bleeding risk factors. A new bleeding risk score termed HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (&gt; 65 years), Drugs/alcohol concomitantly) was calculated, incorporating risk factors from the derivation cohort. Results: Fifty-three (1.5%) major bleeds occurred during 1-year follow-up. The annual bleeding rate increased with increasing risk factors. The predictive accuracy in the overall population using significant risk factors in the derivation cohort (C statistic 0.72) was consistent when applied in several subgroups. Application of the new bleeding risk score (HAS-BLED) gave similar C statistics except where patients were receiving antiplatelet agents alone or no antithrombotic therapy, with C statistics of 0.91 and 0.85, respectively. Conclusion: This simple, novel bleeding risk score (HAS-BLED) provides a practical tool to assess the individual bleeding risk of real-world patients with AF, potentially supporting clinical decision making regarding antithrombotic therapy in patients with AF. © 2010 American College of Chest Physicians

Diabetes known or newly detected, but not impaired glucose regulation, has a negative influence on 1-year outcome in patients with coronary artery disease: A report from the Euro Heart Survey on diabetes and the heart

Aims: Although diabetes is known to be a major contributor to cardiovascular diseases, as well as an independent predictor for adverse outcomes in patients with coronary artery disease (CAD), information on the prognosis of patients with CAD and newly diagnosed diabetes or impaired glucose regulation (IGR) is scarce. The objective of this study was to explore 1-year outcome in relation to different glucometabolic states of patients participating in the Euro Heart Survey on diabetes and the heart. Methods and results: In 4676 out of 4961 patients, information on the relation between 1-year outcome and glucometabolic state, which was based on oral glucose tolerance test (OGTT) or fasting glucose plasma, was available. A normal glucose metabolism was identified in 947 patients, IGR (impaired fasting glucose or impaired glucose tolerance) in 1116 patients, and diabetes in 1877 patients of whom 1425 were previously diagnosed and 452 newly diagnosed. In total, 736 patients could not be classified, as no OGTT or fasting plasma glucose was performed. Previously recognized and newly detected diabetes was associated with an increased risk of 1-year mortality when compared with patients with normal glucose regulation [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.5-3.8 and HR 2.0, 95% CI 1.1-3.6, respectively)]. IGR, however, could not be identified as an independent predictor for 1-year mortality (HR 1.1, 95% CI 0.6-1.9). Conclusion: This study confirmed that patients with CAD and known diabetes are at high risk for mortality and cardiovascular events and demonstrated that patients with newly diagnosed diabetes are at intermediate risk for adverse outcomes. IGR, however, could not be identified as an independent predictor for adverse outcomes during the 1-year follow-up period. © The European Society of Cardiology 2006. All rights reserved