A randomized multicenter trial comparing the XIENCE everolimus eluting stent with the CYPHER sirolimus eluting stent in the treatment of female patients with de novo coronary artery lesions: The SPIRIT WOMEN study.

BACKGROUND: The comparative performance of different drug-eluting stents (DES) among female patients has not been assessed in a randomized manner. OBJECTIVES: The SPIRIT Women Clinical Evaluation trial compared the durable polymer everolimus-eluting XIENCE stent (DP-EES) with the durable polymer sirolimus-eluting Cypher stent (DP-SES) in women undergoing percutaneous coronary intervention (PCI). METHODS: A total of 455 female patients with stable CAD were randomly assigned to receive DP-EES (n = 304) or DP-SES (n = 151). The powered angiographic outcome of the trial was in-stent late lumen loss (LLL) at 9 months after the index procedure. Secondary angiographic end points included in-segment LLL, in-stent and in-segment binary restenosis and percent diameter stenosis. The primary clinical outcome was a composite of all-cause death, myocardial infarction (MI) or target vessel revascularization (TVR). RESULTS: At 9-month follow-up, in-stent LLL was 0.19±0.38 mm and 0.11±0.37 mm in patients assigned to DP-EES and DP-SES, respectively. The one-sided upper 95% CI of the difference in in-stent LLL between the groups of 0.08 mm was 0.15 and therefore within the pre-specified non-inferiority margin of 0.17 mm (p for non-inferiority = 0.013). However, the test for superiority showed a borderline significant difference in terms of LLL between DP-EES and DP-SES (p for superiority = 0.044). There were no significant differences in binary restenosis (2.0% vs. 0.72%, p = 0.44) and percent diameter stenosis (14.97±12.17 vs. 13.36±10.82, p = 0.19). The rate of definite stent thrombosis at 12 months was lower in patients treated with DP-EES (0% vs. 2.0%, p = 0.036). CONCLUSIONS: Among women undergoing PCI, DP-EES was associated with a small but probably clinically relevant increase in in-stent LLL at 9 months as compared to DP-SES and with a lower risk of definite stent thrombosis at 12 months. TRIAL REGISTRATION: ClinicalTrials.gov NCT01182428. https://clinicaltrials.gov/.

Impact of Bleeding and Bivalirudin Therapy on Mortality Risk in Women Undergoing Percutaneous Coronary Intervention (from the REPLACE-2, ACUITY, and HORIZONS-AMI Trials).

Women have higher bleeding complication and mortality rates after percutaneous coronary interventions (PCI). The contribution of female gender to bleeding and mortality is poorly understood. We evaluated the effect of gender and bleeding on outcomes of patients treated with bivalirudin during PCI by performing a patient-level pooled analysis of 3 randomized controlled trials (the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events, Acute Catheterization and Urgent Intervention Triage strategY, and Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) comparing bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitor (GPI) treatment in patients undergoing PCI. Of 14,784 patients, 7,413 patients received bivalirudin (1,870 women) and 7,371 patients received heparin + GPI (1,910 women). Women had significantly higher 30-day non-coronary artery bypass grafting (CABG)-related major bleeding rates (7.6% vs 3.8%, p <0.0001). After multivariate adjustment, female gender increased the hazard of major bleeding by 80% (hazard ratio 1.80, 95% confidence interval 1.52 to 2.11, p <0.001). Furthermore, women had a higher 1-year mortality rate (3.7% vs 2.7%, p = 0.002) than men; 30-day major bleeding was the strongest independent predictor of 1-year mortality in women (hazard ratio 2.48, 95% confidence interval 1.57 to 3.91, p = 0.001). Bivalirudin therapy in women reduced 30-day non-CABG-related major bleeding (5.6% vs 9.7%, p <0.0001) and 1-year mortality (2.9% vs 4.4%, p = 0.02) compared to standard therapy. In conclusion, in this cohort of patients treated for acute coronary syndrome and ST-segment elevation myocardial infarction, women have a near 2-fold increase in bleeding complications compared to men after PCI. Bleeding complications rather than gender is the strongest independent predictor of 1-year mortality in patients undergoing PCI. Furthermore, we observed a more pronounced clinical benefit in women treated with bivalirudin including a 44% reduction in major bleeding and a significant reduction in mortality rates at 1 year.

Regional and physician specialty-associated variations in the medical management of atherosclerotic renal-artery stenosis.

For people enrolled in Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL), we sought to examine whether variation exists in the baseline medical therapy of different geographic regions and if any variations in prescribing patterns were associated with physician specialty. Patients were grouped by location within the United States (US) and outside the US (OUS), which includes Canada, South America, Europe, South Africa, New Zealand, and Australia. When comparing US to OUS, participants in the US took fewer anti-hypertensive medications (1.9 ± 1.5 vs. 2.4 ± 1.4; P < .001) and were less likely to be treated with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (46% vs. 62%; P < .001), calcium channel antagonist (37% vs. 58%; P < .001), and statin (64% vs. 75%; P < .05). In CORAL, the identification of variations in baseline medical therapy suggests that substantial opportunities exist to improve the medical management of patients with atherosclerotic renal-artery stenosis.

Sex-based differences in bleeding and long term adverse events after percutaneous coronary intervention for acute myocardial infarction: three year results from the HORIZONS-AMI trial.

BACKGROUND: Studies have shown sex-based disparities in ST-segment elevation myocardial infarction (STEMI) management and prognosis. We sought to compare women and men undergoing primary percutaneous coronary intervention (PCI) for STEMI in a large, prospective, contemporary context. METHODS: The Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial randomized 3,602 patients (23.4% women and 76.6% men) with STEMI presenting within 12 hr of onset of symptoms to bivalirudin or heparin plus glycoprotein IIb/IIIa inhibitors and to PCI with drug-eluting or bare metal stents. RESULTS: Compared with men, women presented later after symptom onset and were more often treated with medical management alone (6.9% vs. 4.7%; P = 0.01). Women had significantly higher rates of 3-year major adverse cardiac events (MACE) and major bleeding. After adjusting for baseline differences, female sex remained an independent predictor of major bleeding (hazard ratio [HR] 1.81, 95% confidence interval [CI] 1.41-2.33; P < 0.0001) but not of MACE (HR 1.09; 95% CI 0.91-1.32; P = 0.35). CONCLUSIONS: This study found that women with STEMI are at increased risk of bleeding as compared to men. While female sex may not directly contribute to increased risk of MACE, it is, however, associated with the presence of comorbidities that increase the risk of ischemic events long-term. Further dedicated studies are needed to confirm these findings and to assess strategies to optimize both the initial emergent treatment and long-term management in this high-risk subset. © 2014 Wiley Periodicals, Inc.

Darapladib for preventing ischemic events in stable coronary heart disease.

BACKGROUND: Elevated lipoprotein-associated phospholipase A2 activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A2. METHODS: In a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the components of the primary end point as well as major coronary events (death from coronary heart disease, myocardial infarction, or urgent coronary revascularization for myocardial ischemia) and total coronary events (death from coronary heart disease, myocardial infarction, hospitalization for unstable angina, or any coronary revascularization). RESULTS: During a median follow-up period of 3.7 years, the primary end point occurred in 769 of 7924 patients (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI], 0.85 to 1.03; P=0.20). There were also no significant between-group differences in the rates of the individual components of the primary end point or in all-cause mortality. Darapladib, as compared with placebo, reduced the rate of major coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00; P=0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI, 0.84 to 0.98; P=0.02). CONCLUSIONS: In patients with stable coronary heart disease, darapladib did not significantly reduce the risk of the primary composite end point of cardiovascular death, myocardial infarction, or stroke. (Funded by GlaxoSmithKline; STABILITY ClinicalTrials.gov number, NCT00799903.).

International differences in clinical characteristics, management, and outcomes in acute heart failure patients: better short-term outcomes in patients enrolled in Eastern Europe and Russia in the PROTECT trial.

AIMS: The implications of geographical variation are unknown following adjustment for hospital length of stay (LOS) in heart failure (HF) trials that included patients whether or not they had systolic dysfunction. We investigated regional differences in an international acute HF trial. METHODS AND RESULTS: The PROTECT trial investigated 2033 patients with acute HF and renal dysfunction hospitalized at 173 sites in 17 countries with randomization to rolofylline or placebo. We grouped enrolling countries into six regions. Baseline characteristics, in-hospital management, and outcomes were explored by region. The primary study outcome was 60-day mortality or cardiovascular/renal hospitalization. Secondary outcomes included 180-day mortality. Of 2033 patients, 33% were from Eastern Europe, 19% from Western Europe, 16% from Israel, 15% from North America, 14% from Russia, and 3% from Argentina. Marked differences in baseline characteristics, HF phenotype, in-hospital diuretic and vasodilator strategies, and LOS were observed by region. LOS was shortest in North America and Israel (median 5 days) and longest in Russia (median 15 days). Regional event rates varied significantly. Following multivariable adjustment, region was an independent predictor of the risk of mortality/hospitalization at 60 days, with the lowest risk in Russia (hazard ratio 0.39, 95% confidence interval 0.23-0.64 vs. Western Europe) due to lower rehospitalization; mortality differences were attenuated by 180 days. CONCLUSIONS: In an international HF trial, there were differences in baseline characteristics, treatments, LOS, and rehospitalization amongst regions, but little difference in longer term mortality. Rehospitalization differences exist independent of LOS. This analysis may help inform future trial design and should be externally validated.

Encuesta de reconocimiento de la enfermedad cardiovascular en la mujer por la mujer / Women Survey on Women Awareness of Cardiovascular Disease

En la Argentina, las enfermedades cardiovasculares representan el principal problema de salud de las mujeres. Desde el año 2007 mueren más mujeres que hombres en nuestro país por causa cardiovascular y de acuerdo con las últimas estadísticas vitales publicadas, muere una mujer cada 11 minutos. Evaluar si las mujeres perciben que pueden sufrir enfermedades cardiovasculares así como valorar el grado de conocimiento que tienen sobre estas patologías fueron los objetivos de una encuesta telefónica realizada en una muestra representativa de mujeres de Buenos Aires. Los resultados obtenidos en 600 encuestadas mostraron que la gran mayoría de las mujeres tienen un grado de conocimiento adecuado acerca de los factores de riesgo cardiovascular, de los síntomas de enfermedad coronaria y accidente cerebrovascular y de las conductas que previenen o reducen la probabilidad de enfermarse. Sin embargo, gran parte de las mujeres, y en especial las jóvenes, perciben mucho más al cáncer de mama como un problema de salud que a las enfermedades cardiovasculares. Los resultados obtenidos también muestran que la información que tienen las mujeres sobre las enfermedades cardiovasculares rara vez proviene de sus médicos y mayoritariamente se origina en los medios de comunicación masiva. El hecho de que las mujeres incrementen su percepción sobre el riesgo de padecer enfermedades cardiovasculares podría traducirse en una mayor adopción de conductas preventivas y, ante la eventualidad de presentar un evento cardiovascular agudo, en una pronta consulta y mayor y mejor acceso al tratamiento.

Cardiovascular diseases represent a major health problem for women in Argentina. Since 2007, more women than men die in our country due to heart disease and a woman dies every 11 minutes, according to the latest published vital statistics. We performed a telephone survey in a representative sample of women from Buenos Aires in order to assess whether they are aware they may suffer from cardiovascular diseases and their knowledge about these pathologies. Results from 600 respondents showed that the vast majority of women have an adequate level of knowledge about cardiovascular risk factors, symptoms of heart disease and stroke, as well as behaviors that prevent or reduce the likelihood of becoming ill. However, most women, especially the younger ones, perceive breast cancer as a main health concern rather than cardiovascular diseases. The results also show that women get most of the information about cardiovascular diseases mainly from mass media and rarely from their doctors. Raising women awareness about their risk of suffering heart disease might lead to the adoption of better preventive behaviors and, in the case of an acute cardiovascular event, seek immediate help to have access to the best treatment.

Encuesta de reconocimiento de la enfermedad cardiovascular en la mujer por la mujer / Women Survey on Women Awareness of Cardiovascular Disease

En la Argentina, las enfermedades cardiovasculares representan el principal problema de salud de las mujeres. Desde el año 2007 mueren más mujeres que hombres en nuestro país por causa cardiovascular y de acuerdo con las últimas estadísticas vitales publicadas, muere una mujer cada 11 minutos. Evaluar si las mujeres perciben que pueden sufrir enfermedades cardiovasculares así como valorar el grado de conocimiento que tienen sobre estas patologías fueron los objetivos de una encuesta telefónica realizada en una muestra representativa de mujeres de Buenos Aires. Los resultados obtenidos en 600 encuestadas mostraron que la gran mayoría de las mujeres tienen un grado de conocimiento adecuado acerca de los factores de riesgo cardiovascular, de los síntomas de enfermedad coronaria y accidente cerebrovascular y de las conductas que previenen o reducen la probabilidad de enfermarse. Sin embargo, gran parte de las mujeres, y en especial las jóvenes, perciben mucho más al cáncer de mama como un problema de salud que a las enfermedades cardiovasculares. Los resultados obtenidos también muestran que la información que tienen las mujeres sobre las enfermedades cardiovasculares rara vez proviene de sus médicos y mayoritariamente se origina en los medios de comunicación masiva. El hecho de que las mujeres incrementen su percepción sobre el riesgo de padecer enfermedades cardiovasculares podría traducirse en una mayor adopción de conductas preventivas y, ante la eventualidad de presentar un evento cardiovascular agudo, en una pronta consulta y mayor y mejor acceso al tratamiento.(AU)

Cardiovascular diseases represent a major health problem for women in Argentina. Since 2007, more women than men die in our country due to heart disease and a woman dies every 11 minutes, according to the latest published vital statistics. We performed a telephone survey in a representative sample of women from Buenos Aires in order to assess whether they are aware they may suffer from cardiovascular diseases and their knowledge about these pathologies. Results from 600 respondents showed that the vast majority of women have an adequate level of knowledge about cardiovascular risk factors, symptoms of heart disease and stroke, as well as behaviors that prevent or reduce the likelihood of becoming ill. However, most women, especially the younger ones, perceive breast cancer as a main health concern rather than cardiovascular diseases. The results also show that women get most of the information about cardiovascular diseases mainly from mass media and rarely from their doctors. Raising women awareness about their risk of suffering heart disease might lead to the adoption of better preventive behaviors and, in the case of an acute cardiovascular event, seek immediate help to have access to the best treatment.(AU)

Clinical course of patients with hyponatremia and decompensated systolic heart failure and the effect of vasopressin receptor antagonism with tolvaptan.

BACKGROUND: Patients with decompensated heart failure, volume overload, and hyponatremia are challenging to manage. Relatively little has been documented regarding the clinical course of these patients during standard in-hospital management or with vasopressin antagonism. METHODS AND RESULTS: The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan database was examined to assess the short-term clinical course of patients hospitalized with heart failure and hyponatremia and the effect of tolvaptan on outcomes. In the placebo group, patients with hyponatremia (serum Na(+) <135mEq/L; n = 232), compared with those with normonatremia at baseline (n = 1785), had less relief of dyspnea despite receiving higher doses of diuretics (59.2% vs 69.2% improved; P < .01) and worse long-term outcomes. In the hyponatremia subgroup from the entire trial cohort (n = 475), tolvaptan was associated with greater likelihood of normalization of serum sodium than placebo (58% vs 20% and 64% vs 29% for day 1 and discharge, respectively; P < .001 for both comparisons), greater weight reduction at day 1 and discharge (0.7 kg and 0.8 kg differences, respectively; P < .001 and P = .008), and greater relief of dyspnea (P = .03). Among all hyponatremic patients, there was no effect of tolvaptan on long-term outcomes compared with placebo. In patients with pronounced hyponatremia (<130 mEq/L; n = 92), tolvaptan was associated with reduced cardiovascular morbidity and mortality after discharge (P = .04). CONCLUSIONS: In patients with decompensated heart failure and hyponatremia, standard therapy is associated with less weight loss and dyspnea relief, and unfavorable longer-term outcomes compared to those with normonatremia. Tolvaptan is associated with more favorable in-hospital effects and, possibly, long-term outcomes in patients with severe hyponatremia.

Effect of serelaxin on cardiac, renal, and hepatic biomarkers in the Relaxin in Acute Heart Failure (RELAX-AHF) development program: correlation with outcomes.

OBJECTIVES: The aim of this study was to assess the effects of serelaxin on short-term changes in markers of organ damage and congestion and relate them to 180-day mortality in patients with acute heart failure. BACKGROUND: Hospitalization for acute heart failure is associated with high post-discharge mortality, and this may be related to organ damage. METHODS: The Pre-RELAX-AHF (Relaxin in Acute Heart Failure) phase II study and RELAX-AHF phase III study were international, multicenter, double-blind, placebo-controlled trials in which patients hospitalized for acute heart failure were randomized within 16 h to intravenous placebo or serelaxin. Each patient was followed daily to day 5 or discharge and at days 5, 14, and 60 after enrollment. Vital status was assessed through 180 days. In RELAX-AHF, laboratory evaluations were performed daily to day 5 and at day 14. Plasma levels of biomarkers were measured at baseline and days 2, 5, and 14. All-cause mortality was assessed as a safety endpoint in both studies. RESULTS: Serelaxin reduced 180-day mortality, with similar effects in the phase II and phase III studies (combined studies: N = 1,395; hazard ratio: 0.62; 95% confidence interval: 0.43 to 0.88; p = 0.0076). In RELAX-AHF, changes in markers of cardiac (high-sensitivity cardiac troponin T), renal (creatinine and cystatin-C), and hepatic (aspartate transaminase and alanine transaminase) damage and of decongestion (N-terminal pro-brain natriuretic peptide) at day 2 and worsening heart failure during admission were associated with 180-day mortality. Serelaxin administration improved these markers, consistent with the prevention of organ damage and faster decongestion. CONCLUSIONS: Early administration of serelaxin was associated with a reduction of 180-day mortality, and this occurred with fewer signs of organ damage and more rapid relief of congestion during the first days after admission.

Clinical course and predictive value of congestion during hospitalization in patients admitted for worsening signs and symptoms of heart failure with reduced ejection fraction: findings from the EVEREST trial.

AIMS: Signs and symptoms of congestion are the most common cause for hospitalization for heart failure (HHF). The clinical course and prognostic value of congestion during HHF has not been systemically characterized. METHODS AND RESULTS: A post hoc analysis was performed of the placebo group (n = 2061) of the EVEREST trial, which enrolled patients within 48 h of admission (median ~24 h) for worsening HF with an EF ≤ 40% and two or more signs or symptoms of fluid overload [dyspnoea, oedema, or jugular venous distension (JVD)] for a median follow-up of 9.9 months. Clinician-investigators assessed patients daily for dyspnoea, orthopnoea, fatigue, rales, pedal oedema, and JVD and rated signs and symptoms on a standardized 4-point scale ranging from 0 to 3. A modified composite congestion score (CCS) was calculated by summing the individual scores for orthopnoea, JVD, and pedal oedema. Endpoints were HHF, all-cause mortality (ACM), and ACM + HHF. Multivariable Cox regression models were used to evaluate the risk of CCS at discharge on outcomes at 30 days and for the entire follow-up period. The mean CCS obtained after initial therapy decreased from the mean ± SD of 4.07 ± 1.84 and the median (25th, 75th) of 4 (3, 5) at baseline to 1.11 ± 1.42 and 1 (0, 2) at discharge. At discharge, nearly three-quarters of study participants had a CCS of 0 or 1 and fewer than 10% of patients had a CCS >3. B-type natriuretic peptide (BNP) and amino terminal-proBNP, respectively, decreased from 734 (313, 1523) pg/mL and 4857 (2251, 9642) pg/mL at baseline to 477 (199, 1079) pg/mL, and 2834 (1218, 6075) pg/mL at discharge/Day 7. A CCS at discharge was associated with increased risk (HR/point CCS, 95% CI) for a subset of endpoints at 30 days (HHF: 1.06, 0.95-1.19; ACM: 1.34, 1.14-1.58; and ACM + HHF: 1.13, 1.03-1.25) and all outcomes for the overall study period (HHF: 1.07, 1.01-1.14; ACM: 1.16, 1.09-1.24; and ACM + HHF 1.11, 1.06-1.17). Patients with a CCS of 0 at discharge experienced HHF of 26.2% and ACM of 19.1% during the follow-up. CONCLUSION: Among patients admitted for worsening signs and symptoms of HF and reduced EF, congestion improves substantially during hospitalization in response to standard therapy alone. However, patients with absent or minimal resting signs and symptoms at discharge still experienced a high mortality and readmission rate.

Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial.

BACKGROUND: Serelaxin, recombinant human relaxin-2, is a vasoactive peptide hormone with many biological and haemodynamic effects. In a pilot study, serelaxin was safe and well tolerated with positive clinical outcome signals in patients with acute heart failure. The RELAX-AHF trial tested the hypothesis that serelaxin-treated patients would have greater dyspnoea relief compared with patients treated with standard care and placebo. METHODS: RELAX-AHF was an international, double-blind, placebo-controlled trial, enrolling patients admitted to hospital for acute heart failure who were randomly assigned (1:1) via a central randomisation scheme blocked by study centre to standard care plus 48-h intravenous infusions of placebo or serelaxin (30 µg/kg per day) within 16 h from presentation. All patients had dyspnoea, congestion on chest radiograph, increased brain natriuretic peptide (BNP) or N-terminal prohormone of BNP, mild-to-moderate renal insufficiency, and systolic blood pressure greater than 125 mm Hg. Patients, personnel administering study drug, and those undertaking study-related assessments were masked to treatment assignment. The primary endpoints evaluating dyspnoea improvement were change from baseline in the visual analogue scale area under the curve (VAS AUC) to day 5 and the proportion of patients with moderate or marked dyspnoea improvement measured by Likert scale during the first 24 h, both analysed by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00520806. FINDINGS: 1161 patients were randomly assigned to serelaxin (n=581) or placebo (n=580). Serelaxin improved the VAS AUC primary dyspnoea endpoint (448 mm × h, 95% CI 120-775; p=0·007) compared with placebo, but had no significant effect on the other primary endpoint (Likert scale; placebo, 150 patients [26%]; serelaxin, 156 [27%]; p=0·70). No significant effects were recorded for the secondary endpoints of cardiovascular death or readmission to hospital for heart failure or renal failure (placebo, 75 events [60-day Kaplan-Meier estimate, 13·0%]; serelaxin, 76 events [13·2%]; hazard ratio [HR] 1·02 [0·74-1·41], p=0·89] or days alive out of the hospital up to day 60 (placebo, 47·7 [SD 12·1] days; serelaxin, 48·3 [11·6]; p=0·37). Serelaxin treatment was associated with significant reductions of other prespecified additional endpoints, including fewer deaths at day 180 (placebo, 65 deaths; serelaxin, 42; HR 0·63, 95% CI 0·42-0·93; p=0·019). INTERPRETATION: Treatment of acute heart failure with serelaxin was associated with dyspnoea relief and improvement in other clinical outcomes, but had no effect on readmission to hospital. Serelaxin treatment was well tolerated and safe, supported by the reduced 180-day mortality. FUNDING: Corthera, a Novartis affiliate company.

The occupational effects of interventional cardiology: results from the WIN for Safety survey.

AIMS: Interventional cardiologists are amongst the most intensive radiation users within medicine. To assess the implications of this usage, the "Women In Innovation" Group (WIN) created a web-based survey called "WIN for Safety" distributed through the European Association of Percutaneous Coronary Intervention (EAPCI) to all catheterisation laboratory healthcare professionals, enquiring about radiation protection measures, compliance with monitoring, health (orthopaedic issues), radiation-associated problems (cataracts and cancer) and restrictions imposed upon the pregnant female. METHODS AND RESULTS: In total, there were 615 participants: 72.8% were interventional cardiologists. Most (73.5%) of them were male and 63.3% were aged 31-50 years. A radiation collar badge was used by the majority (64.4%) and the most frequently utilised protective measure was the thyroid shield (87.2%). Potential illnesses related to radiation exposure included 19.5% orthopaedic problems (back/neck/hip pain), 5.5% varicose veins, 2.4% blood count problems and 2.0% cataracts. Notably, an association between orthopaedic problems and years of exposure was found (p=0.001). Overall, only 2.2% had ever been diagnosed with a cancer, with a trend for more females to be affected (4.4% vs. 1.8%; p=0.067). Finally, 62.1% have restrictions imposed upon the pregnant female in the working environment. CONCLUSIONS: Awareness of radiation in the field of interventional cardiology is essential. The main risk is orthopaedic problems and measures should be taken for prevention. Cancer has not been demonstrated to be a direct consequence; however, we should remain vigilant and monitor individuals.

SPIRIT Women, evaluation of the safety and efficacy of the XIENCE V everolimus-eluting stent system in female patients: referral time for coronary intervention and 2-year clinical outcomes.

AIMS: SPIRIT Women is the first interventional trial dedicated exclusively to women, focusing on symptoms at presentation, referral time to coronary intervention and the safety and performance of the XIENCE V stent. METHODS AND RESULTS: SPIRIT Women is a prospective, open-label, multicentre study in which 1,573 women were enrolled at 73 sites outside the United States. The primary endpoint is the composite of all death, Academic Research Consortium (ARC) defined myocardial infarction (MI) and target vessel revascularisation (TVR) at one year. Data collected included symptoms at presentation and referral to coronary intervention. To allow comparison by gender, the latter were compared to data from male patients from the SPIRIT V study. The one- and two-year composite of all death, MI and TVR was 12% and 15%, respectively. Target lesion revascularisation (TLR) and stent thrombosis (definite and probable) rates were 2.4% and 0.59%, respectively, at one year and 3.6% and 0.73%, at two years. The total referral time for coronary intervention in women was four days longer than for men in the SPIRIT V study. CONCLUSIONS: The XIENCE V stent is safe and effective with low TLR and stent thrombosis rates. More efforts remain to be made to increase the awareness of women and physicians of the risk for coronary artery disease (CAD).

Efficacy of oral tolvaptan in acute heart failure patients with hypotension and renal impairment.

AIMS: Although congestion is the main reason for admission in patients with worsening acute heart failure syndromes, patients presenting with low SBP and renal impairment often do not respond adequately to and may not tolerate traditional diuretic therapy. We sought to determine the short-term hemodynamic effects of tolvaptan in this high-risk population. METHODS: In a subset analysis of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan trial, 759 patients (18% of total) had elevated blood urea nitrogen (BUN) (> 20  mg/dl) and low SBP (<105  mmHg) at admission. Of these, 386 were randomized to tolvaptan and 373 to placebo. RESULTS: Demographics and baseline characteristics were similar in both groups. Greater reductions from baseline in body weight were observed for tolvaptan (1.63 ±â€Š 2.00 vs. 0.76  ±â€Š 1.75  kg, P  <  0.0001 at day 1 and 3.23  ±  3.36 vs. 2.10  ±â€Š 3.47  kg, P  <  0.0001 at day 7 or discharge). Greater increases in serum sodium concentration were also observed in the tolvaptan group as early as day 1 (4.41  ±  3.67 vs. 1.32  ±â€Š 3.93  mEq/l, P  <  0.0001) and persisted through day 7 or discharge (4.79  ±â€Š 4.89 vs. 1.25  ±â€Š 5.00  mEq/l, P  <  0.0001). Similarly, improvements in patient-reported dyspnea and investigator-assessed orthopnea were significantly greater in the tolvaptan group as early as day 1 of treatment. These changes were not associated with significant differences in heart rate, SBP, DBP or serum creatinine between patients in the two treatment groups during hospitalization. In-hospital mortality rates (total and cause-specific) were comparable to patients who had presented with SBP more than 105  mmHg and BUN less than 20  mg/dl. CONCLUSION: In this subgroup analysis of patients with hypotension and renal impairment, tolvaptan improved symptoms, reduced body weight and increased serum sodium as early as inpatient day 1 without adversely affecting blood pressure or renal function.

A comprehensive, longitudinal description of the in-hospital and post-discharge clinical, laboratory, and neurohormonal course of patients with heart failure who die or are re-hospitalized within 90 days: analysis from the EVEREST trial.

Hospitalization for worsening chronic heart failure results in high post-discharge mortality, morbidity, and cost. However, thorough characterization, soon after discharge of patients with early post-discharge events has not been previously performed. The objectives of this study were to describe the baseline, in-hospital, and post-discharge clinical, laboratory, and neurohormonal profiles of patients hospitalized for worsening heart failure with reduced ejection fraction (EF) who die or are re-admitted for cardiovascular (CV) causes within 90 days of initial hospitalization. Retrospective analysis of 4,133 patients hospitalized for worsening heart failure with EF ≤40% in the Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST) trial, which randomized patients to tolvaptan or placebo, both in addition to standard therapy. Clinical and laboratory parameters were obtained within 48 h of admission, during hospitalization, and post-discharge weeks 1, 4, 8, and every 8 weeks thereafter for a median of 9.9 months. Patients with events within 90 days were compared with those with later/no events. All-cause mortality (ACM) and CV re-hospitalization were independently adjudicated. Within 90 days of admission, 395 patients (9.6%) died and 801 patients (19.4%) were re-hospitalized for CV causes. Significant baseline and longitudinal differences were seen between groups with early versus later (>90 days) or no events at 12 months post-randomization. Post-discharge outcomes were similar in the tolvaptan and placebo groups. Patients with early post-discharge events experienced clinically significant worsening in signs and symptoms, laboratory values, and neurohormonal parameters soon after discharge. Identifying these abnormalities may facilitate efforts to reduce post-discharge mortality and re-hospitalization.

Avaliação do stent coronário eluidor de everolimus XIENCE TM V na cpopulação feminina latino-americana do estudo de braço único SPIRIT Women: acompanhamento clínico de um ano / Evaluation of the XIENCE TM V everolimus-eluting coronary stent system in the female latin american population of the SPIRIT Women single-arm study: one-year clinical follow-up data

INTRODUÇÃO: Os estudos com stents farmacológicos têm avaliado predominantemente populações masculinas de descendência europeia. O estudo de braço único SPIRIT Women avalia o stent eluidor de everolimus XIENCE TM V em lesões de novo complexas em uma população feminina do mundo real, incluindo pacientes latino-americanas. Esta análise permite compreender como essa população responde ao implante de stent, comparativamente a pacientes não-latino-americanas. MÉTODOS: Das 1.572 pacientes matriculadas em 73 locais fora dos Estados Unidos, 138 (9%) foram recrutadas na Argentina, no Brasil e na Venezuela. RESULTADOS: As lesões-alvo tinham diâmetro de referência do vaso entre 2,25 mm e 4 mm e extensão da lesão ≤ 28 mm. As características basais foram semelhantes entre os grupos, com exceção de maior prevalência de hipertensão arterial, infarto do miocárdio (IM) de parede anterior e história familiar de doença arterial coronária na coorte latino-americana. As lesões tendiam a ser mais complexas em mulheres latino-americanas, com menor diâmetro de referência do vaso-alvo, maior extensão da lesão, maior excentricidade e angulação e mais lesões tipo B2/C. Os eventos foram adjudicados de acordo com as definições do Academic Research Consortium. Em um ano, o desfecho combinado de morte por todas as causas, IM e revascularização do vaso-alvo (RVA) foi de 12,1% na população não-latino-americana e de 10,1% na população latino-americana (P = 0,58). CONCLUSÕES: Em um ano, os baixos índices de eventos cardíacos adversos, incluindo trombose do stent, falha da lesão-alvo, morte cardíaca, IM e RVA nas mulheres latino-americanas foram comparáveis aos das mulheres não-latino-americanas, apesar da maior complexidade das lesões. Esses resultados demonstram a segurança e a eficácia do stent XIENCE TM V nessa pequena coorte de pacientes latino-americanas, à semelhança do que é observado com populações maiores e mais variadas.

BACKGROUND: Drug-eluting stent trials have predominantly examined male populations of European descent. SPIRIT Women single-arm study evaluates the XIENCE TM V everolimus-eluting stent in complex de novo lesions in a real world female population, including Latin American patients. This analysis provides an insight into how this population responds to stenting when compared to non-Latin American patients. METHODS: Of the 1,572 patients enrolled from 73 non-US sites, 138 (9%) were recruited from Argentina, Brazil and Venezuela. RESULTS: Target lesions had reference vessel diameter ranging between 2.25 mm and 4 mm and lesion length ≤ 28 mm. Baseline characteristics were similar between the groups, with exception to a higher prevalence of hypertension, anterior myocardial infarction (MI) and family history of coronary artery disease in the Latin American cohort. Lesions tended to be more complex in Latin American women with a smaller reference vessel diameter, longer lesion length, increased eccentricity and angulation, and more type B2/C lesions. Events were adjudicated according to the guidelines of the Academic Research Consortium. At 1 year, the composite endpoint of death, MI and target vessel revascularization (TVR) was 12.1% in the non-Latin American population and 10.1% in the Latin American population (P = 0.58). CONCLUSIONS: At 1 year, the low rates of adverse cardiac events, including stent thrombosis, target lesion failure, cardiac death, MI and TVR in Latin American women were comparable to those of the non-Latin American women, despite the higher complexity of lesions. These results demonstrate the safety and efficacy of the XIENCE TM V stent in this small cohort of Latin American patients, in line with what is observed in larger and more varied populations.

Evaluating the safety of very short-term (10 days) dual antiplatelet therapy after Genous™ bio-engineered R stent™ implantation: the multicentre pilot Genous trial.

AIMS: Percutaneous coronary stenting is synonymous with dual antiplatelet therapy, ranging from four weeks to lifelong. However, even short-term (four weeks) therapy with aspirin and thienopyridines is occasionally contraindicated. No study has ever appraised very short-term dual antiplatelet therapy after stenting. We thus aimed to exploit the pro-healing features of the Genous™ Bio-engineered R stent™ (Genous) (OrbusNeich Medical Technologies, Hong Kong, People's Republic of China) and evaluate the safety of a 10-day dual antiplatelet regimen after its implantation in up to 50 patients. METHODS AND RESULTS: Forty-nine consecutive patients with de novo lesions located in vessels able to receive a 2.5 mm Genous stent were included. After stenting, they received lifelong aspirin plus clopidogrel for 10 days. The primary endpoint of the study was sudden cardiac death, myocardial infarction or angiographic evidence of stent thrombosis ascribable to the study stent. Almost 70% of patients effectively discontinued clopidogrel nine to 11 days after stenting. At three-month clinical follow-up, no patient had died or reached the primary endpoint (95%; confidence interval 0-7.3%). Repeat revascularisation occurred instead in three (6.1%[2.1-16.5%]), with target lesion revascularisation in two (4.1%[1.1-13.7%]). CONCLUSIONS: Even very short-term dual antiplatelet therapy seems safe after coronary stenting with Genous in de novo coronary artery lesions located in secondary branch vessels. This preliminary exploratory study gives some support to planning a large trial to test the hypothesis of short dual antiplatelet therapy following Genous stent implantation.

Changes in renal function during hospitalization and soon after discharge in patients admitted for worsening heart failure in the placebo group of the EVEREST trial.

AIM: To provide an in-depth clinical characterization and analysis of outcomes of the patients hospitalized for heart failure (HF) who subsequently develop worsening renal function (WRF) during hospitalization or soon after discharge. METHODS AND RESULTS: Of the 4133 patients hospitalized with worsening HF and reduced left ventricular ejection fraction (LVEF) (≤40%) in the EVEREST trial, 2072 were randomized to tolvaptan, a selective vasopressin-2 receptor antagonist, and 2061 were randomized to placebo, both in addition to standard therapy. This analysis included the 2021 (98%) patients in the placebo group with a complete set of renal function parameters. Renal function parameters and clinical variables were measured prospectively during hospitalization and after discharge. Worsening renal function was defined as an increase in sCr ≥0.3 mg/dL during the in-hospital (randomization to discharge or Day 7) and post-discharge (discharge or Day 7 to 4 weeks post-discharge) periods. Blood pressure (BP), body weight (BW), natriuretic peptides (NPs), and congestion score were correlated with WRF. The prognostic value of baseline renal function at admission and WRF during hospitalization and post-discharge on long-term outcomes were assessed using a Cox proportional hazards model adjusted for other baseline covariates. At randomization, 53.2% of patients had moderately or severely reduced estimated glomerular filtration rate (eGFR) (<60.0 mL/min/1.73 m2). Worsening renal function was observed in 13.8% in-hospital and 11.9% post-discharge. Worsening renal function during hospitalization and post-discharge was associated with greater reductions in BP, BW, and NPs. Baseline renal dysfunction as well as in-hospital and post-discharge WRF were predictive of a composite endpoint of cardiovascular (CV) mortality/HF rehospitalization. CONCLUSION: The prevalence of renal dysfunction is high in patients hospitalized for HF with reduced LVEF. Worsening renal function may occur not only during hospitalization, but also in the early post-discharge period. Since worsening renal function during hospitalization is associated with a significant decrease in signs and symptoms of congestion, body weight and natriuretic peptides, which are good prognostic indicators, worsening renal function during hospitalization as an endpoint in clinical trials should be re-evaluated.

Effects of tolvaptan on physician-assessed symptoms and signs in patients hospitalized with acute heart failure syndromes: analysis from the efficacy of vasopressin antagonism in heart failure outcome study with tolvaptan (EVEREST) trials.

BACKGROUND: A rapid and sustained relief of heart failure (HF) symptoms and signs is an important goal of management in patients hospitalized for acute HF syndromes (AHFS). To date, no novel therapy in AHFS have been shown to improve signs and symptoms throughout hospitalization. This study explores the clinical effects of tolvaptan, a vasopressin-2-receptor antagonist, in addition to standard medical therapies on physician-assessed signs and symptoms in hospitalized AHFS patients. METHODS: The EVEREST trial randomized 4,133 patients admitted with worsening HF and reduced ejection fraction (≤ 40%) within 48 hours after hospital admission. On each inpatient day, investigators assessed dyspnea, orthopnea, fatigue, jugular venous distension (JVD), rales, and pedal edema by predefined ordinal scales. Responder analyses were performed for each sign and symptom, with significant clinical response defined as a change in one point on the measurement scale. RESULTS: Post hoc analysis demonstrated greater likelihood of clinical improvement in physician-assessed dyspnea, edema, orthopnea, and JVD among tolvaptan-treated subjects (P < .05) as early as inpatient day 1. This difference was observed throughout hospitalization only for JVD and orthopnea through day 3. CONCLUSION: The addition of tolvaptan to standard therapy for AHFS improves physician-assessed signs and symptoms during hospitalization without serious adverse short- or long-term effects.