An Update on Anti-thrombotic Therapy Following Transcatheter Aortic Valve Implantation: Expert Cardiologist Opinion from a UK and Ireland Delphi Group.

Transcatheter aortic valve implantation (TAVI) is an effective and established treatment for symptomatic aortic stenosis. However, there is a lack of consensus concerning the need for peri- and post-procedural anti-thrombotic medication. Contemporary guidelines recommend that anti-thrombotic therapy is balanced against a patient's bleeding risk following TAVI, but do not fully consider the evolving evidence base. The purpose of the Delphi panel recommendations presented here is to provide a consensus elicited from a panel of experts who regularly prescribe anti-thrombotic therapy post-TAVI. The goal was to address evidence gaps across four key topics: anti-thrombotic therapy (anti-platelet and/or anti-coagulant) in TAVI patients in sinus rhythm; anti-thrombotic therapy in TAVI patients with AF; direct oral anti-coagulants versus vitamin K antagonists; and the need for UK/Ireland specific guidance. This consensus statement aims to inform clinical decision-making by providing a concise, evidence-based summary of best practice for prescribing anti-thrombotic therapies following TAVI and highlights areas where further research is needed.

Sex Differences in Oral Anticoagulation Therapy in Patients Hospitalized With Atrial Fibrillation: A Nationwide Cohort Study.

Background Important disparities in the treatment and outcomes of women and men with atrial fibrillation (AF) are well recognized. Whether introduction of direct oral anticoagulants has reduced disparities in treatment is uncertain. Methods and Results All patients who had an incident hospitalization from 2010 to 2019 with nonvalvular AF in Scotland were included in the present cohort study. Community drug dispensing data were used to determine prescribed oral anticoagulation therapy and comorbidity status. Logistic regression modeling was used to evaluate patient factors associated with treatment with vitamin K antagonists and direct oral anticoagulants. A total of 172 989 patients (48% women [82 833 of 172 989]) had an incident hospitalization with nonvalvular AF in Scotland between 2010 and 2019. By 2019, factor Xa inhibitors accounted for 83.6% of all oral anticoagulants prescribed, while treatment with vitamin K antagonists and direct thrombin inhibitors declined to 15.9% and 0.6%, respectively. Women were less likely to be prescribed any oral anticoagulation therapy compared with men (adjusted odds ratio [aOR], 0.68 [95% CI, 0.67-0.70]). This disparity was mainly attributed to vitamin K antagonists (aOR, 0.68 [95% CI, 0.66-0.70]), while there was less disparity in the use of factor Xa inhibitors between women and men (aOR, 0.92 [95% CI, 0.90-0.95]). Conclusions Women with nonvalvular AF were significantly less likely to be prescribed vitamin K antagonists compared with men. Most patients admitted to the hospital in Scotland with incident nonvalvular AF are now treated with factor Xa inhibitors and this is associated with fewer treatment disparities between women and men.

Two-year follow-up of the NEVO ResElution-I(NEVO RES-I) trial: a randomised, multicentre comparison of the NEVO sirolimus-eluting coronary stent with the TAXUS Liberté paclitaxel-eluting stent in de novo native coronary artery lesions.

AIMS: To assess the two-year clinical follow-up of the NEVO RES-1 study, a randomised comparison between the NEVO™ sirolimus-eluting coronary stent system (NEVO SES) and the TAXUS Liberté™ paclitaxel-eluting stent (TAXUS PES). METHODS AND RESULTS: NEVO RES-I randomised 394 patients with single de novo lesions with a maximum length of 28 mm and diameter of 2.5-3.5 mm to NEVO SES (n=202) versus TAXUS PES (n=192). Six-month angiographic results demonstrated the superiority of the NEVO SES over the TAXUS PES for the primary endpoint, in-stent late loss. At one year, MACE (death, emergent CABG, TLR, and MI) in the NEVO SES group was 6.1% versus 10.6% in the TAXUS PES group (p=0.139). After two years, MACE was 7.2% in the NEVO SES group versus 13.0% in TAXUS PES group (p=0.086). Corresponding rates of TLR were 3.6% versus 7.6% (p=0.116). No ARC-defined definite or probable stent thromboses (ST) were reported with NEVO SES while two occurred with TAXUS PES. CONCLUSIONS: While not designed or powered for clinical endpoints, individual and composite clinical endpoints numerically favoured the NEVO SES over the TAXUS PES, with continued separation over time up to two years. No ARC-defined definite or probable ST was reported in the NEVO SES group at two years. Clinical trial identifier: NCT00606333 http://www.clinicaltrials.gov.

A prospective randomized multicenter comparison of balloon angioplasty and infrapopliteal stenting with the sirolimus-eluting stent in patients with ischemic peripheral arterial disease: 1-year results from the ACHILLES trial.

OBJECTIVES: The study investigated the efficacy and safety of a balloon expandable, sirolimus-eluting stent (SES) in patients with symptomatic infrapopliteal arterial disease. BACKGROUND: Results of infrapopliteal interventions using balloon angioplasty and/or bare stents are limited by a relatively high restenosis rate, which could be potentially improved by stabilizing the lesion with a SES. METHODS: Two hundred patients (total lesion length 27 ± 21 mm) were randomized to infrapopliteal SES stenting or percutaneous transluminal balloon angioplasty (PTA). The primary endpoint was 1-year in-segment binary restenosis by quantitative angiography. RESULTS: Ninety-nine and 101 patients (mean age 73.4 years; 64% diabetics) were randomized to SES and PTA, respectively (8 crossover bailout cases to SES). At 1 year, there were lower angiographic restenosis rates (22.4% vs. 41.9%, p = 0.019), greater vessel patency (75.0% vs. 57.1%, p =0.025), and similar death, repeat revascularization, index-limb amputation rates, and proportions of patients with improved Rutherford class for SES versus PTA. CONCLUSIONS: SES implantation may offer a promising therapeutic alternative to PTA for treatment of infrapopliteal peripheral arterial disease.

Myocardial function may improve equally in diabetic patients following both multivessel percutaneous coronary intervention and coronary artery bypass grafting: results from a CARDia trial substudy.

AIMS: The CARDia (Coronary Artery Revascularization in Diabetes) trial compared coronary artery bypass grafting (CABG) and optimal percutaneous coronary intervention (PCI) in diabetic patients with multivessel coronary disease. Patients enrolled had symptoms of myocardial ischaemia. As symptom assessment is flawed in diabetic patients, a substudy was undertaken to compare the extent to which these revascularization strategies alter reversible ischaemia. METHODS AND RESULTS: Seventy-one patients underwent stress echo at baseline and at 6 months. A 17-segment echocardiographic wall motion score index (WMSI) was assigned at baseline [WMSI(pre)] and at 6 months [WMSI(post)]. An overall score defined the difference: WMSI(∂) = WMSI(pre)--WMSI(post). Of 71 patients recruited, 42 underwent PCI and 29 CABG. Mean WMSI(pre) in the PCI group was 1.63 and mean WMSI(post) was 1.32. Mean WMSI(pre) in the CABG group was 1.69 and mean WMSI(post) was 1.46. The PCI WMSI(∂) was 0.31 and CABG WMSI(∂) was 0.23 (P = 0.8). Of 42 PCI patients, 39 demonstrated ischaemia at baseline. At 6 months 31 had improvements in ischaemia (79%), 5 showed no improvement, and 3 ischaemia worsened. Of 29 CABG patients, 23 demonstrated ischaemia at baseline. At 6 months, 20 had improvements in ischaemia (87%), 2 had no improvement, and in 1 ischaemia worsened. No difference was seen in the number of patients with improvements in reversible ischaemia between PCI and CABG [79 vs. 87%, (P = 0.9)]. CONCLUSION: Optimal revascularization in diabetic patients with multivessel disease remains controversial. This subset analysis of the CARDia trial suggests both PCI and CABG achieve similar improvement in reversible ischaemia.

Randomized comparison of percutaneous coronary intervention with coronary artery bypass grafting in diabetic patients. 1-year results of the CARDia (Coronary Artery Revascularization in Diabetes) trial.

OBJECTIVES: The purpose of this study was to compare the safety and efficacy of percutaneous coronary intervention (PCI) with stenting against coronary artery bypass grafting (CABG) in patients with diabetes and symptomatic multivessel coronary artery disease. BACKGROUND: CABG is the established method of revascularization in patients with diabetes and multivessel coronary disease, but with advances in PCI, there is uncertainty whether CABG remains the preferred method of revascularization. METHODS: The primary outcome was a composite of all-cause mortality, myocardial infarction (MI), and stroke, and the main secondary outcome included the addition of repeat revascularization to the primary outcome events. A total of 510 diabetic patients with multivessel or complex single-vessel coronary disease from 24 centers were randomized to PCI plus stenting (and routine abciximab) or CABG. The primary comparison used a noninferiority method with the upper boundary of the 95% confidence interval (CI) not to exceed 1.3 to declare PCI noninferior. Bare-metal stents were used initially, but a switch to Cypher (sirolimus drug-eluting) stents (Cordis, Johnson & Johnson, Bridgewater, New Jersey) was made when these became available. RESULTS: At 1 year of follow-up, the composite rate of death, MI, and stroke was 10.5% in the CABG group and 13.0% in the PCI group (hazard ratio [HR]: 1.25, 95% CI: 0.75 to 2.09; p=0.39), all-cause mortality rates were 3.2% and 3.2%, and the rates of death, MI, stroke, or repeat revascularization were 11.3% and 19.3% (HR: 1.77, 95% CI: 1.11 to 2.82; p=0.02), respectively. When the patients who underwent CABG were compared with the subset of patients who received drug-eluting stents (69% of patients), the primary outcome rates were 12.4% and 11.6% (HR: 0.93, 95% CI: 0.51 to 1.71; p=0.82), respectively. CONCLUSIONS: The CARDia (Coronary Artery Revascularization in Diabetes) trial is the first randomized trial of coronary revascularization in diabetic patients, but the 1-year results did not show that PCI is noninferior to CABG. However, the CARDia trial did show that multivessel PCI is feasible in patients with diabetes, but longer-term follow-up and data from other trials will be needed to provide a more precise comparison of the efficacy of these 2 revascularization strategies. (The Coronary Artery Revascularisation in Diabetes trial; ISRCTN19872154).

The Bypass Angioplasty Revascularization in Type 1 and Type 2 Diabetes Study: 5-year follow-up of revascularization with percutaneous coronary intervention versus coronary artery bypass grafting in diabetic patients with multivessel disease.

OBJECTIVES: The aim of the Bypass Angioplasty Revascularization in Type 1 and Type 2 Diabetes study was to assess percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) as treatments for multivessel coronary artery disease in diabetic patients. BACKGROUND: CABG is generally regarded as the treatment of choice for multivessel coronary artery disease in diabetes. PCI is an alternative therapy. The Bypass Angioplasty Revascularization in Type 1 and 2 Diabetes study compared long-term outcomes of CABG with PCI in diabetic patients treated during the bare-metal stent era. METHODS: We collected data prospectively on consecutive diabetic patients undergoing index angiography in a single tertiary centre from January 1998 to December 2001. Multivessel coronary artery disease was defined as more than 50% luminal stenosis in two or more vessels. Exclusion criteria included left main stem disease and previous revascularization. RESULTS: Two hundred and thirty-five eligible patients underwent CABG and 237 PCI. Median follow-up was 5.4 years. There were 46 (19%) deaths in the CABG group and 43 (18%) deaths in the PCI group (P = 0.64). Cox regression analysis revealed baseline glomerular filtration rate (hazard ratio 0.979, P = 0.001), age (hazard ratio 1.034, P = 0.033), urgent procedure (hazard ratio 1.97, P = 0.008) and myocardial infarction within 4 weeks (hazard ratio 2.494, P = 0.041) to be important predictors of outcome. At 5 years, there was no mortality difference (hazard ratio 1.0) following adjustment for baseline characteristics, and the Kaplan-Meier survival curves were similar. A subanalysis of patients with three-vessel disease revealed similar outcomes with both PCI and CABG. CONCLUSION: In the Bypass Angioplasty Revascularization in Type 1 and Type 2 Diabetes study, diabetic patients with multivessel coronary artery disease had similar long-term mortality whether treated with CABG or PCI, the revascularization determined by the physician's choice. This was despite the frequent use of a strategy of selective revascularization in the PCI arm. Randomized trials comparing PCI and CABG specifically in diabetes, that is, Coronary Artery Revascularization in Diabetes and Future Revascularization Evaluation in Diabetes Mellitus: Optimal Management, will show whether drug-eluting stents further enhance PCI outcomes over the long term.

The influence of the route of oestrogen administration on serum levels of cortisol-binding globulin and total cortisol.

OBJECTIVES: Oral oestrogen preparations increase total cortisol concentration by increasing circulating cortisol-binding globulin (CBG) levels. Transdermal oestrogen treatments are being used increasingly in clinical practice. These topical preparations may have less of an effect on CBG and hence on total serum cortisol levels by reducing hepatic oestrogen exposure. The purpose of this study was to compare the effects of oral and topical oestrogen treatments on CBG, total serum cortisol and salivary cortisol levels. DESIGN AND PATIENTS: This was a single-centre, cross-sectional study of 37 women aged 33 +/- 6 years (mean +/- SD). Fourteen women were using oral oestrogen therapy, eight were using transdermal therapy and 15 were oestrogen-naïve control subjects. MEASUREMENTS: Following a screening visit, the subjects attended the endocrine investigation unit following an overnight fast. Blood and salivary samples were taken from 0830 to 0930 h between days 10 and 18 of the menstrual cycle (where appropriate). RESULTS: Total serum cortisol concentrations were 67% higher in those receiving oral oestrogen when compared to control subjects (660.9 +/- 89.9 vs. 395.4 +/- 53.2 nmol/l, P < 0.001). Values in those receiving transdermal oestrogen (334.7 +/- 72.0 nmol/l) were no different from the control group. CBG levels were higher in those on oral oestrogen therapy (110.9 +/- 19.6 mg/l, P < 0.001) when compared with either those on transdermal oestrogen (51.0 +/- 5.4 mg/l) or the control population (49.0 +/- 11.8 mg/l). Similar salivary cortisol concentrations were recorded in the three groups (controls 13.8 +/- 2.6 nmol/l, oral oestrogen 15.5 +/- 2.6 nmol/l, transdermal oestrogen 15.7 +/- 3.9 nmol/l). CONCLUSIONS: Oral oestrogen-containing preparations increase total cortisol levels by increasing circulating CBG concentration. These effects were not seen in patients using transdermal oestrogen replacement. Although further studies are indicated, it is probably unnecessary to routinely discontinue transdermal oestrogen replacement when performing an assessment of the hypothalamic-pituitary-adrenal (HPA) axis or evaluating adequacy of hydrocortisone replacement.