Summary Background Drug-eluting stents with durable biocompatible or biodegradable polymers have been developed to address the risk of thrombosis associated with first-generation drug-eluting stents. ...We aimed to compare the safety and efficacy of a biodegradable polymer-coated biolimus-eluting stent with a thin-strut everolimus-eluting stent coated with a durable biocompatible polymer. Methods This open-label, prospective, randomised, controlled, non-inferiority trial was undertaken at 12 sites across Europe. We used limited exclusion criteria (age >18 years, life expectancy >5 years, reference vessel diameter 2·0–4·0 mm) to enrol patients eligible for percutaneous coronary intervention. Patients were randomly allocated (2:1) by computer-generated random numbers to receive either a biodegradable polymer biolimus-eluting stent (Nobori, Terumo, Tokyo, Japan) or a durable fluoropolymer-based everolimus-eluting stent (Xience V or Prime, Abbott Vascular, Santa Clara, CA, USA, or Promus, Boston Scientific, Natick, MA, USA). The primary endpoint was a composite of safety (cardiac death and non-fatal myocardial infarction) and efficacy (clinically indicated target vessel revascularisation) at 12 months, analysed by intention to treat. Patients received dual antiplatelet therapy for 12 months after discharge. The trial is registered with ClinicalTrials.gov , number NCT01233453. Findings From Jan 12, 2009, to Feb 7, 2011, we enrolled 2707 patients (4025 lesions), 1795 of whom were assigned to receive the biolimus-eluting stent (2638 lesions) and 912 to an everolimus-eluting stent (1387 lesions). 2688 (99·3%) patients completed 12 months' follow-up. Significantly more patients in the biolimus-eluting stent group received a non-assigned stent than did those in the everolimus-eluting stent group (105 5·9% vs 19 2·1%; p<0·0001). The primary endpoint occurred in 93 (5·2%) patients in the biolimus-eluting stent group and 44 (4·8%) patients in the everolimus-eluting stent group at 12 months (relative risk 1·07 95% CI 0·75–1·52; pnon-inferiority <0·0001). Analysis per protocol did not change the outcome of this trial (pnon-inferiority <0·0001). Interpretation Biodegradable polymer biolimus-eluting stents are as safe and efficacious as the current standard of a thin-strut everolimus-eluting stent with a durable biocompatible polymer. We need to follow-up patients for longer to show whether the biolimus-eluting stent reduces the risk of stent thrombosis after 1 year when compared with the everolimus-eluting stent. Funding Terumo Europe (Leuven, Belgium) and the Research Foundation of the Cardiology Department, Maasstad Hospital (Rotterdam, Netherlands).
Summary Background Some countries fortify flour with folic acid to prevent neural tube defects but others do not, partly because of concerns about possible cancer risks. We aimed to assess any ...effects on site-specific cancer rates in the randomised trials of folic acid supplementation, at doses higher than those from fortification. Methods In these meta-analyses, we sought all trials completed before 2011 that compared folic acid versus placebo, had scheduled treatment duration at least 1 year, included at least 500 participants, and recorded data on cancer incidence. We obtained individual participant datasets that included 49 621 participants in all 13 such trials (ten trials of folic acid for prevention of cardiovascular disease n=46 969 and three trials in patients with colorectal adenoma n=2652). All these trials were evenly randomised. The main outcome was incident cancer (ignoring non-melanoma skin cancer) during the scheduled treatment period (among participants who were still free of cancer). We compared those allocated folic acid with those allocated placebo, and used log-rank analyses to calculate the cancer incidence rate ratio (RR). Findings During a weighted average scheduled treatment duration of 5·2 years, allocation to folic acid quadrupled plasma concentrations of folic acid (57·3 nmol/L for the folic acid groups vs 13·5 nmol/L for the placebo groups), but had no significant effect on overall cancer incidence (1904 cancers in the folic acid groups vs 1809 cancers in the placebo groups, RR 1·06, 95% CI 0·99–1·13, p=0·10). There was no trend towards greater effect with longer treatment. There was no significant heterogeneity between the results of the 13 individual trials (p=0·23), or between the two overall results in the cadiovascular prevention trials and the adenoma trials (p=0·13). Moreover, there was no significant effect of folic acid supplementation on the incidence of cancer of the large intestine, prostate, lung, breast, or any other specific site. Interpretation Folic acid supplementation does not substantially increase or decrease incidence of site-specific cancer during the first 5 years of treatment. Fortification of flour and other cereal products involves doses of folic acid that are, on average, an order of magnitude smaller than the doses used in these trials. Funding British Heart Foundation, Medical Research Council, Cancer Research UK, Food Standards Agency.
Summary Background Everolimus-eluting stent (EES) reduces the risk of restenosis in elective percutaneous coronary intervention. However, the use of drug-eluting stent in patients with ST-segment ...elevation myocardial infarction (STEMI) is still controversial. Data regarding the performance of second-generation EES in this setting are scarce. We report the 1-year result of the EXAMINATION (clinical Evaluation of the Xience-V stent in Acute Myocardial INfArcTION) trial, comparing EES with bare-metal stents (BMS) in patients with STEMI. Methods This multicentre, prospective, randomised, all-comer controlled trial was done in 12 medical centres in three countries. Between Dec 31, 2008, and May 15, 2010, we recruited patients with STEMI up to 48 h after the onset of symptoms requiring emergent percutaneous coronary intervention. Patients were randomly assigned (ratio 1:1) to receive EES or BMS. Randomisation was in blocks of four or six patients, stratified by centre and centralised by telephone. Patients were masked to treatment. The primary endpoint was the patient-oriented combined endpoint of all-cause death, any recurrent myocardial infarction, and any revascularisation at 1 year and was analysed by intention to treat. The secondary endpoints of the study included the device-oriented combined endpoint of cardiac death, target vessel myocardial infarction or target lesion revascularisation, and rates of all cause or cardiac death, recurrent myocardial infarction, target lesion or target vessel revascularisation, stent thrombosis, device and procedure success, and major and minor bleeding. This trial is registered with ClinicalTrials.gov , number NCT00828087. Findings Of the 1504 patients randomised, 1498 patients were randomly assigned to receive EES (n=751) or BMS (n=747). The primary endpoint was similar in both groups (89 11·9% of 751 patients in the EES group vs 106 14·2% of 747 patients in the BMS group; difference −2·34 95% CI −5·75 to 1·07; p=0·19). Device-oriented endpoint (44 5·9% in the EES group vs 63 8·4% in the BMS group; difference −2·57 95% CI −5·18 to 0·03; p=0·05) did not differ between groups, although rates of target lesion and vessel revascularisation were significantly lower in the EES group (16 2·1% vs 37 5·0%, p=0·003, and 28 3·7% vs 51 6·8%, p=0·0077, respectively). Rates of all cause (26 3·5% for EES vs 26 3·5% for BMS, p=1·00) or cardiac death (24 3·2% for EES vs 21 2·8% for BMS, p=0·76) or myocardial infarction (10 1·3% vs 15 2·0%, p=0·32) did not differ between groups. Stent thrombosis rates were significantly lower in the EES group (4 0·5% patients with definite stent thrombosis in the EES group vs 14 1·9% in the BMS group and seven 0·9% patients with definite or probable stent thrombosis in the EES group vs 19 2·5% in the BMS group, both p=0·019). Although device success rate was similar between groups, procedure success rate was significantly higher in the EES group (731 97·5% vs 705 94·6%; p=0·0050). Finally, Bleeding rates at 1 year were comparable between groups (29 3·9% patients in the EES group vs 39 5·2% in the BMS group; p=0·19). Interpretation The use of EES compared with BMS in the setting of STEMI did not lower the patient-oriented endpoint. However, at the stent level both rates of target lesion revascularisation and stent thrombosis were reduced in recipients of EES. Funding Spanish Heart Foundation.
Cancer Risk in Transgender People de Blok, Christel J M; Dreijerink, Koen M A; den Heijer, Martin
Endocrinology and metabolism clinics of North America,
06/2019, Volume:
48, Issue:
2
Journal Article
Peer reviewed
Gender-affirming hormonal treatment (HT) in transgender people is considered safe in general, but the question regarding (long-term) risk on sex hormone-related cancer remains. Because the risk on ...certain types of cancer differs between men and women, and some of these differences are attributed to exposure to sex hormones, the cancer risk may be altered in transgender people receiving HT. Although reliable epidemiologic data are sparse, the available data will be discussed in this article. Furthermore, recommendations for cancer screening and prevention will be discussed as well as whether to withdraw HT at time of a cancer diagnosis.
Abstract Objectives This analysis investigates the 5-year outcomes of the biodegradable polymer biolimus-eluting stent (BP-BES) and durable polymer everolimus-eluting stent (DP-EES) in an all-comers ...population undergoing percutaneous coronary intervention. Background Recent 1- and 3-year results from randomized trials have indicated similar safety and efficacy outcomes of BP-BES and DP-EES. Whether benefits of the biodegradable polymer device arise over longer follow-up is unknown. Moreover, in-depth, prospective, long-term follow-up data on metallic drug-eluting stents with durable or biodegradable polymers are scarce. Methods The COMPARE II trial (Abluminal Biodegradable Polymer Biolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent) was a prospective, randomized, multicenter, all-comers trial in which 2,707 patients were randomly allocated (2:1) to BP-BES or DP-EES. The pre-specified endpoint at 5 years was major adverse cardiac events, a composite of cardiac death, nonfatal myocardial infarction, or target vessel revascularization. Results Five-year follow-up was available in 2,657 patients (98%). At 5 years, major adverse cardiac events occurred in 310 patients (17.3%) in the BP-BES group and 142 patients (15.6%) in the DP-EES group (p = 0.26). The rate of the combined safety endpoint all-cause death or myocardial infarction was 15.0% in the BP-BES group versus 14.8% in the DP-EES group (p = 0.90), whereas the efficacy measure target vessel revascularization was 10.6% versus 9.0% (p = 0.18), respectively. Interestingly, definite stent thrombosis rates did not differ between groups (1.5% for BP-BES vs. 0.9% for DP-EES; p = 0.17). Conclusions The 5-year analysis comparing biodegradable polymer-coated BES and the durable polymer-coated EES confirms the initial early- and mid-term results regarding similar safety and efficacy outcomes in this all-comers percutaneous coronary intervention population.
Background ST-elevation myocardial infarctions (STEMI) caused by proximal left-anterior descending (LAD) lesions have more myocardium at risk and worse outcomes than those located in other segments. ...The aim is to compare outcomes of patients with STEMI and proximal-LAD lesions treated with bare-metal stents (BMS) versus everolimus-eluting stents (EES). Methods The EXAMINATION trial randomized 1498 STEMI patients to BMS versus EES. The primary end point was the patient-oriented combined of all-cause death, any-recurrent myocardial infarction (MI) and any-revascularization. The secondary end point included the device-oriented combined of cardiac death, target-vessel MI and target-lesion revascularization (TLR). Results STEMI with a proximal-LAD occlusion was observed in 290 patients (BMS = 132 and EES = 158). Both groups were similar except for diabetes (12.9% vs 24.1%; P = .016). At 1 year, the primary end point was observed in 18.9% and 9.5% of patients treated with BMS and EES, respectively ( P = .023). The secondary end point was observed in 11.4% and 5.1%, respectively ( P = .053). There were no differences in cardiac death (4.5% vs 3.8%; P = .750) and MI (1.5% vs 0%; P = .121). BMS had higher rate of TLR compared to EES (6.8% vs 1.3%; P = .014). Patients with proximal-LAD STEMI had higher mortality than patients with non proximal-LAD STEMI (5.5% vs 2.9%; P = .027). Proximal-LAD lesions treated with BMS tended to increase the risk of the primary end point compared with other segments (18.9% vs 13.0%; P = .079). However, EES implanted in proximal-LAD had similar outcomes compared with other locations (9.5% vs 12.0%; P = .430). Adjusting for confounders, the interaction between BMS and proximal-LAD location was associated with the primary end point. Conclusion Patients with STEMI and proximal-LAD lesions treated with EES have better outcomes compared with BMS at 1 year. Although further investigations are required, it seems reasonable to consider EES for proximal-LAD STEMI-lesions.
Objective We designed a large prospective study to explore the relationship between maternal homocysteine concentrations and related B vitamins and birthweight. Study Design Blood was sampled from ...pregnant women at 30-34 weeks of gestation and their newborn infants (n = 366). Results Concentrations of all analytes were higher in umbilical cord compared with maternal samples. Birthweight was related negatively to maternal homocysteine (r = –0.12) but not related to maternal cobalamin, methylmalonic acid, and folate (r = 0.02, r = 0.06, and r = 0.04, respectively). Regression analysis revealed smoking (β = –313; 95% confidence interval CI, –479 to –149), gestational age (β = 150; 95% CI, 118–182), female sex (β = –146; 95% CI, –256 to –35), and parity (β = 104; 95% CI, 37–171) as strong determinants of birthweight. Maternal homocysteine, cobalamin, methylmalonic acid, and folate were not determinants of birthweight in multivariate analysis. Conclusion Maternal homocysteine and B vitamins are not related to birthweight in a multivariate model that was adjusted for potential confounders.
PDF
