Secondary prevention advices after cardiovascular index event: From drug prescription to risk factors control in real world practice

The present study aims at evaluating the achievement of blood pressure, lipid and blood glucose targets, healthy lifestyle changes and appropriate drug prescription/adherence in patients attending secondary prevention/CR ambulatory visit after index cardiovascular event in a time period ranging 1 to 5 year. At ambulatory visit, a predetermined set of data collection was used, including demographic data, cardiovascular risk factors and lifestyle habits, type and time of index event, current symptoms, physical sign, biochemistry and current medical treatment (including type and dosage). Cardiovascular risk profile (smoking habits, physical activity and body weight), secondary prevention goals (LDL-cholesterol, blood pressure, resting heart rate, glycated haemoglobin level) and the use of recommended drugs were also evaluated and categorized. Study population consisted of 800 patients [644 men (84.5%), aged 69±10.9 years)]. Cardiovascular index events were coronary artery bypass graft (CABG) (20%) ST segment elevation myocardial infarction (STEMI) (28%), non-ST segment elevation myocardial infarction (NSTEMI) (21%) and stable angina (13%) by unstable angina (13%) and stroke (5%). About 30% of patients was symptomatic (angina or dyspnoea) at the time of ambulatory visit. Major comorbidities were hypertension (73%), dyslipidaemia (64%) and diabetes (40%). More than 80% of patients achieved target levels for blood pressure. Patients that have participated to cardiac rehabilitation programmes after cardiovascular index event showed best achievement in blood pressure target (83.8% vs 76.8%, p=0.02). LDL-cholesterol target (<70 mg/dl) was achieved in about 2/3 of patients; HbA1c target (<7%) was achieved in 56.4% of diabetic population. About 75% of study cohort was treated with RAAS inhibitors, 85% with beta-blockers, 92% with statins and 87% with acetylsalicylic acid. All drugs were increasingly adopted from index event. Implementing secondary prevention guidelines into the 'real world' clinical practice in "late" interval from 1 to 5 years after a cardiovascular event improved risk factors control and appropriate drug prescription. Whether these improvements translated into prognostic advantages remains to be elucidated

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%

1021-57 Cardiac Involvement and Anticardiolipin Antibodies Levels in Primary Antiphospholipid Syndrome: A Transesophageal Study

Myocardial involvement and valvular lesions are frequently observed in Primary Antiphospholipid Syndrome (PAPS), particularly in patients (pts) with clinical manifestations (arterial and/or venous thrombosis or recurrent fetal loss). To evaluate whether high anticardiolipin antibodies (aCL-a) levels are able to produce severe cardiac involvement or embolic sources (spontaneous echocontrast, masses or vegetations), we studied 30 PAPS pts (3 M and 27 F; aged 37±10 yrs) by means of multiplane transesophageal echocardiography (TEE). compared with 20-matched controls (C). We analyzed systo-diastolic LV function; abnormal leaflet thickness was &gt;3mm for mitral or tricuspid valve (MVT or TVT) and &gt;2mm for aortic (AVT). aCL-a measured using standard ELISA method were expressed in GPL U, (normal value &lt;15U).ResultsAll PAPS pts presented normal systo-diastolic LV function. We considered 3 groups (Gr) according to aCL-a levels: Gr I (low-positive, 15–35 U), mean MVT 2.7±0.5mm; Gr II (moderate-positive, 35–100 U), mean MVT 3.4±0.8mm; Gr III (high-positive,&gt;100 U), mean MVT 3.5±0.9mm.Gr I (n=9)Gr II (n=7)Gr III (n=14)MVT2 (22%)5 (71%)11 (78%)no MVT7 (78%)2 (29%)3 (22%)Chi square=7.74,P&lt;0.057/14 (50%) Gr III pts showed: 3 mild mitral stenosis, 2 TVT and 2 AVT. AVT was also found in Gr I (2) and Gr II (1). PAPS pts had high incidence of embolic sources: 11% Gr I, 2B% Gr II and 63% Gr III (chi square=6,95, p&lt;0.05).Conclusions1) Multiplane TEE is useful to detect significative valvular abnormalities and embolic sources in PAPS pts. 2) High levels (&gt;100U) of aCL-a are associated to MVT and embolic sources, indicative of high thromboembolic risk. 3) Follow-up studies are necessary to attribute to high aCL-a levels a predictive value in PAPS pts

Prevalence and prognostic value of elevated urinary albumin excretion in patients with chronic heart failure data from the GISSI-Heart failure trial

Background-Increased urinary excretion of albumin is an early sign of kidney damage and a risk factor for progressive cardiovascular and renal diseases and heart failure. There is, however, only limited information on the prevalence and prognostic role of urinary albumin excretion in patients with established chronic heart failure. Methods and Results-A total of 2131 patients enrolled in 76 sites participating in the GISSI-Heart Failure trial provided a first morning spot sample of urine at any of the clinical visits scheduled in the trial to calculate the urinary albumin-to-creatinine ratio. The relation between log-transformed urinary albumin-to-creatinine ratio and all-cause mortality (428 deaths, time from urine collection to event or censoring) was evaluated with Cox multivariable models adjusted for all significant risk factors at the time of urine collection, in the study population, and in patients without diabetes or hypertension. Almost 75% of the patients had normal urinary albumin excretion, but 19.9% had microalbuminuria (30 to 299 mg/g creatinine) and 5.4% had overt albuminuria ( 65300 mg/g). There was a progressive, significant increase in the adjusted rate of mortality in the study population (hazard ratio, 1.12; 95% CI, 1.05 to 1.18 per 1-U increase of log(urinary albumin-to-creatinine ratio), P=0.0002) and in the subgroup of patients without diabetes or hypertension. Randomized treatments (n-3 polyunsaturated fatty acids or rosuvastatin) had no major impact on albumin excretion. Conclusions-Independently of diabetes, hypertension, or renal function, elevated albumin excretion is a powerful prognostic marker in patients with chronic heart failure. \ua9 2010 American Heart Association, Inc

Serum uric acid and outcomes in patients with chronic heart failure through the whole spectrum of ejection fraction phenotypes: Analysis of the ESC-EORP Heart Failure Long-Term (HF LT) Registry

Background: Retrospective analyses of clinical trials indicate that elevated serum uric acid (sUA) predicts poor outcome in heart failure (HF). Uric acid can contribute to inflammation and microvascular dysfunction, which may differently affect different left ventricular ejection fraction (LVEF) phenotypes. However, role of sUA across LVEF phenotypes is unknown. Objectives: We investigated sUA association with outcome in a prospective cohort of HF patients stratified according to LVEF. Methods: Through the Heart Failure Long-Term Registry of the European Society of Cardiology (ESC-EORP-HFLT), 4,438 outpatients were identified and classified into: reduced (&lt;40% HFrEF), mid-range (40-49% HFmrEF), and preserved (&gt;= 50% HFpEF) LVEF. Endpoints were the composite of cardiovascular death/HF hospitalization, and individual components. Results: Median sUA was 6.72 (IQ:5.48-8.20) mg/dl in HFrEF, 6.41 (5.02-7.77) in HFmrEF, and 6.30 (5.20-7.70) in HFpEF. At a median 372-day follow-up, the composite endpoint occurred in 648 (13.1%) patients, with 176 (3.6%) deaths and 538 (10.9%) HF hospitalizations. Compared with lowest sUA quartile (Q), Q-III and Q-IV were significantly associated with the composite endpoint (adjusted HR 1.68: 95% CI 1.11-2.54; 2.46: 95% CI 1.66-3.64, respectively). By univariable analyses, HFrEF and HFmrEF patients in Q-III and Q-IV, and HFpEF patients in Q-IV, showed increased risk for the composite endpoint (P&lt;0.05 for all); after model-adjustment, significant association of sUA with outcome persisted among HFrEF in Q-IV, and HFpEF in Q-III-IV. Conclusions: In a large, contemporary-treated cohort of HF outpatients, sUA is an independent prognosticator of adverse outcome, which can be appreciated in HErEF and HFpEF patients

Discontinuation of anti-PD1 in advanced melanoma: an observational retrospective study from the Italian Melanoma Intergroup

Background: Immunotherapy has improved the survival of patients with stage IV melanoma. In responders, clinical benefits may be long-lasting and persist even after treatment discontinuation. The optimal duration of anti-PD1 (anti-Programmed cell death-1) therapy in metastatic melanoma patients remains to be elucidated. Moreover, limited data are available on clinical outcomes of patients that discontinued anti-PD1 immunotherapy in a real-life setting. The aim of this study was to evaluate the progression-free survival (PFS) in patients with metastatic melanoma who interrupted anti-PD-1 treatment in the in the absence of disease progression. Methods: We retrospectively reviewed patients with advanced/metastatic melanoma treated with anti-PD1 immunotherapy at 23 Italian Melanoma Intergroup (IMI) centres. The study investigated the risk of relapse in patients who stopped anti-PD1 therapy due to CR (Complete response), treatment-related toxicity, or by their own choice after a long period of treatment. Clinical and biological factors associated with or without recurrence were evaluated. Results: The study population included 237 patients. The median age of patients was 68.9&nbsp;years (standard deviation: 13; range 33-95). The median time on treatment was 33&nbsp;months (standard deviation: 18,&nbsp;7; range 1-98). Among the 237 patients, 128 (54%) interrupted the anti-PD1 for CR, 74 patients (31.2%) for adverse events (37 patients in CR, 27 patients in partial response (PR), ten patients in stable disease (SD), and 35 patients (14.8%) by their own choice (12 patients in CR, 17 patients in PR, and 6 patients in SD). After a mean follow-up of 21&nbsp;months (range 1-81), PFS&nbsp;after anti-PD1 discontinuation was 85.7%. Thirty-four patients (14.3%) developed disease progression after a median of 12&nbsp;months (range 1-35): ten patients (29.4%) after discontinuation in CR, 17 patients (50%) after discontinuation for treatment-related toxicity (seven in CR, five in PR, five in SD), and seven (20.6%) after discontinuation due to the patient's decision (two&nbsp;in CR, four in PR, one in SD). Only 7.8% of patients who interrupted in CR (10/128), along with 23% of patients who interrupted for limiting toxicity (17/74) and 20% of patients who interrupted by their own choice (7/35), developed recurrence. Regarding patients who discontinued therapy because of CR, we observed a negative association between recurrence and site of primary melanoma, especially mucosal sites (p&nbsp;=&nbsp;&lt;0.05, HR (Hazard ratio) 15.57 IC (confidence interval) 95% 2.64-91.73). Moreover, M1b patients who achieved a CR showed a lower number of relapses (p&nbsp;=&nbsp;&lt;0.05, HR 3.84 IC 95% 1.40-8.48). Conclusions: This study shows in a real-life setting that, with anti-PD-1 therapy, long-lasting responses, can be maintained after anti-PD1 interruption. In 70.6% of cases, recurrences were observed among patients who did not obtain a CR at treatment discontinuation

Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial

Background: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. Methods: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer. Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely removed by surgery, any pathological tumour size, and axillary nodal status. Key exclusion criteria were hormone replacement therapy, recurrent or metastatic disease, previous treatment with tamoxifen, and another malignancy in the previous 10 years. Patients were randomly assigned in an equal ratio to one of six treatment groups: oral anastrozole (1 mg per day), exemestane (25 mg per day), or letrozole (2·5 mg per day) tablets upfront for 5 years (upfront strategy) or oral tamoxifen (20 mg per day) for 2 years followed by oral administration of one of the three aromatase inhibitors for 3 years (switch strategy). Randomisation was done by a computerised minimisation procedure stratified for oestrogen receptor, progesterone receptor, and HER2 status; previous chemotherapy; and pathological nodal status. Neither the patients nor the physicians were masked to treatment allocation. The primary endpoint was disease-free survival. The minimum cutoff to declare superiority of the upfront strategy over the switch strategy was assumed to be a 2% difference in disease-free survival at 5 years. Primary efficacy analyses were done by intention to treat; safety analyses included all patients for whom at least one safety case report form had been completed. Follow-up is ongoing. This trial is registered with the European Clinical Trials Database, number 2006-004018-42, and ClinicalTrials.gov, number NCT00541086. Findings: Between March 9, 2007, and July 31, 2012, 3697 patients were enrolled into the study. After a median follow-up of 60 months (IQR 46–72), 401 disease-free survival events were reported, including 211 (11%) of 1850 patients allocated to the switch strategy and 190 (10%) of 1847 patients allocated to upfront treatment. 5-year disease-free survival was 88·5% (95% CI 86·7–90·0) with the switch strategy and 89·8% (88·2–91·2) with upfront treatment (hazard ratio 0·89, 95% CI 0·73–1·08; p=0·23). 5-year disease-free survival was 90·0% (95% CI 87·9–91·7) with anastrozole (124 events), 88·0% (85·8–89·9) with exemestane (148 events), and 89·4% (87·3 to 91·1) with letrozole (129 events; p=0·24). No unexpected serious adverse reactions or treatment-related deaths occurred. Musculoskeletal side-effects were the most frequent grade 3–4 events, reported in 130 (7%) of 1761 patients who received the switch strategy and 128 (7%) of 1766 patients who received upfront treatment. Grade 1 musculoskeletal events were more frequent with the upfront schedule than with the switch schedule (924 [52%] of 1766 patients vs 745 [42%] of 1761 patients). All other grade 3–4 adverse events occurred in less than 2% of patients in either group. Interpretation: 5 years of treatment with aromatase inhibitors was not superior to 2 years of tamoxifen followed by 3 years of aromatase inhibitors. None of the three aromatase inhibitors was superior to the others in terms of efficacy. Therefore, patient preference, tolerability, and financial constraints should be considered when deciding the optimal treatment approach in this setting. Funding: Italian Drug Agency