Gender differences with short-term vs 12 months dual antiplatelet therapy in patients with acute coronary syndrome treated with the COMBO dual therapy stent: 2-years follow-up results of the REDUCE trial.

BACKGROUND: Gender differences in the thrombotic and bleeding risk have been suggested to condition the benefits of antithrombotic therapies in Acute Coronary Syndrome (ACS) patients, and mainly among those undergoing percutaneous coronary interventions with drug eluting stents (DES). The impact of gender on the optimal duration of dual antiplatelet therapy (DAPT) in ACS patients is still unexplored and was, therefore, the aim of the present sub-study. METHODS: REDUCE was a prospective, multicenter, randomized investigator-initiated study designed to enroll 1500 ACS patients after treatment with the COMBO Dual Stent Therapy, based on a noninferiority design. Patients were randomized in a 1:1 fashion to either 3 or 12 months of DAPT. Primary study endpoint was a composite of all-cause mortality, myocardial infarction, definite/probable stent thrombosis (ST), stroke, target-vessel revascularization (TVR) and bleedings (BARC II, III, V) at 12 months. Secondary endpoints were cardiovascular mortality and the individual components of the primary endpoint within 24 months. RESULTS: From June 2014 to May 2016 300 women and 1196 men were included in the study. Among them, 43.7% of females and 51.9% of males were assigned to the 3 months DAPT treatment. Baseline characteristics were well matched between the two arms, with the exception of a lower rate of TIMI flow < 3 (p = 0.04), lower systolic blood pressure (p = 0.05) and use of spironolactone (p = 0.006) among women and a more advanced age (p = 0.05) among men receiving a short-term DAPT. At a mean follow-up of 525 (± 198) days, no difference in the primary endpoint was observed according to DAPT duration in both females [6.9% vs 5.9%, HR (95% CI) = 1.19 (0.48-2.9), p = 0.71] and males [8.2% vs 9%, HR (95% CI) = 0.92 (0.63-1.35), p = 0.67; p INT = 0.20]. Results were confirmed after correction for baseline differences [females: adjusted HR (95% CI) = 1.12 (0.45-2.78), p = 0.81; males: adjusted HR (95% CI) = 0.90 (0.61-1.32), p = 0.60]. Comparable rates of survival, thrombotic (MI, stent thrombosis, TVR, stroke) and bleeding events were observed with the two DAPT strategies, with no impact of gender. CONCLUSIONS: The present study shows that among ACS patients randomized in the REDUCE trial, a 3 months DAPT strategy offers comparable results as compared to a standard 12 months DAPT at 2-years follow-up in both male and female gender.

Effects of radial versus femoral artery access in patients with acute myocardial infarction: A large centre prospective registry.

AIM: This study sought to assess whether radial artery access improves clinical outcomes in patients presenting with acute myocardial infarction compared with femoral artery access. METHODS: This is a single-centre, prospective observational registry of all STEMI and NSTEMI patients who underwent coronary angiography and/or primary PCI in the period January 2010 to December 2013. Primary endpoint was 30-day all-cause mortality. Choice of access was left to the discretion of the cardiologist. Differences in the risk of death at 30 days between patients undergoing transradial intervention versus transfemoral intervention was assessed on an intention-to-treat comparison. RESULTS: Retrospective analysis of prospectively collected data was performed in 3580 patients with an acute coronary syndrome who underwent coronary angiography, of which 1310 had radial artery access. PCI was performed in 77 % of the patients. Before propensity score matching, patients who underwent transradial intervention and those intended to undergo transfemoral approach differed significantly in intra-aortic balloon pump use (1.7 % vs. 6.7 %, p < 0.001), and Killip class (Killip 1: 10.8 % vs. 17.3 %, p < 0.001). 30-day mortality rates were 1.7 % in the transradial group and 4.6 % in the transfemoral group (p < 0.001). After matching on the propensity score, the hazard ratio for 30-day mortality in the transradial group was 0.56 (95 % CI: 0.29-1.07, p = 0.08). CONCLUSION: This registry-based study showed that radial access is associated with improved outcome in patients with an acute coronary syndrome. However, this difference was no longer significant after multivariate and propensity score adjustment for differences in baseline characteristics.

EU-CaRE study: Could exercise-based cardiac telerehabilitation also be cost-effective in elderly?

BACKGROUND: The role of cardiac rehabilitation (CR) is well established in the secondary prevention of ischemic heart disease. Unfortunately, the participation rates across Europe remain low, especially in elderly. The EU-CaRE RCT investigated the effectiveness of a home-based mobile CR programme in elderly patients that were not willing to participate in centre-based CR. The initial study concluded that a 6-month home-based mobile CR programme was safe and beneficial in improving VO2peak when compared with no CR. OBJECTIVE: To assess whether a 6-month guided mobile CR programme is a cost-effective therapy for elderly patients who decline participation in CR. METHODS: Patients were enrolled in a multicentre randomised clinical trial from November 11, 2015, to January 3, 2018, and follow-up was completed on January 17, 2019, in a secondary care system with 6 cardiac institutions across 5 European countries. A total of 179 patients who declined participation in centre-based CR and met the inclusion criteria consented to participate in the European Study on Effectiveness and Sustainability of Current Cardiac Rehabilitation Programs in the Elderly trial. The data of patients (n = 17) that were lost in follow-up were excluded from this analysis. The intervention (n = 79) consisted of 6 months of mobile CR programme with telemonitoring, and coaching based on motivational interviewing to stimulate patients to reach exercise goals. Control patients did not receive any form of CR throughout the study period. The costs considered for the cost-effectiveness analysis of the RCT are direct costs 1) of the mobile CR programme, and 2) of the care utilisation recorded during the observation time from randomisation to the end of the study. Costs and outcomes (utilities) were compared by calculation of the incremental cost-effectiveness ratio. RESULTS: The healthcare utilisation costs (P = 0.802) were not significantly different between the two groups. However, the total costs were significantly higher in the intervention group (P = 0.040). The incremental cost-effectiveness ratio for the primary endpoint VO2peak at 6 months was €1085 per 1-unit [ml/kg/min] improvement in change VO2peak and at 12 months it was €1103 per 1 unit [ml/kg/min] improvement in change VO2peak. Big differences in the incremental cost-effectiveness ratios for the primary endpoint VO2peak at 6 months and 12 months were present between the adherent participants and the non-adherent participants. CONCLUSION: From a health-economic point of view the home-based mobile CR programme is an effective and cost-effective alternative for elderly cardiac patients who are not willing to participate in a regular rehabilitation programme to improve cardiorespiratory fitness. The change of QoL between the mobile CR was similar for both groups. Adherence to the mobile CR programme plays a significant role in the cost-effectiveness of the intervention. Future research should focus on the determinants of adherence, on increasing the adherence of patients and the implementation of comprehensive home-based mobile CR programmes in standard care.

The extent of ST elevation and ST deviation as predictors of mortality in ST-segment elevation myocardial patients planned to undergo primary percutaneous coronary intervention.

BACKGROUND: Only few data are available on the predictive value of ST deviation (both ST elevation and depression). Therefore, we have examined the predictive value of ST elevation and ST deviation in STEMI patients on 30-day and long term mortality. METHODS: All STEMI patients with an interpretable diagnostic electrocardiogram, who were referred to the Isala hospital and were planned to undergo a primary coronary intervention (pPCI) in the period 2001 until 2009, were prospectively registered in a cohort study. These patients were divided in tertiles based on the cumulative (cum) ST deviation (D1, D2 and D3) and cum ST elevation (E1, E2 and E3), as assessed by an independent core-lab. RESULTS: In total, 4513 patients were registered. 30-day mortality increased with cum ST deviation (0-9 mm: 1.9%, > 9-16 mm: 2.4%, > 16 mm: 3.9%, P = 0.001), but not significant with cum ST elevation. Long term mortality increased with cum ST-deviation (0-9 mm: 18.6%, > 9-16 mm: 22.1%, > 16 mm: 25.7%, P < 0.001) and with cum ST-elevation (0-6mm: 19.7%, > 6-11 mm: 22.7%, > 11 mm: 24.2%, P = 0.070). After multivariable adjustment using Cox proportional Hazard models, cum ST deviation (D1: reference, D2: HR: 1.09 95% CI (0.67-1.77), D3: HR: 1.76 95% CI (1.14-2.73)) was independently associated with 30-day mortality. Both cum ST deviation (D1: reference, D2: HR: 1.14 95% CI (0.98-1.34), D3: HR: 1.32 95% CI (1.13-1.53)) and ST elevation (E1: reference, E2: HR: 1.17 95% CI (1.00-1.38), E3: HR: 1.21 95% CI (1.04-1.42)) were independently associated with long term mortality. CONCLUSIONS: Besides ST elevation, taking the extent of ST depression into account improves the predictive value of the diagnostic 12 lead electrocardiogram especially for 30-day mortality in STEMI patients who are planned to undergo pPCI.

[Prophylactic perioperative beta-blockade reduces cardiac morbidity and mortality following non-cardiac surgery in patients at risk]. / Profylactische perioperatieve beta-blokkade ter vermindering van cardiale morbiditeit en sterfte bij risicopatiënten die een niet-cardiale operatie ondergaan.

Approximately 5% of all patients undergoing non-cardiac surgery suffer some form of perioperative cardiac morbidity, usually preceded by myocardial ischaemia. In the Netherlands, the cardiac mortality following non-cardiac surgery is 0.68%. The patient groups at risk for cardiac complications are: age 65 years and older, patients with coronary artery disease or risk factors for coronary artery disease, and those undergoing major surgery. The period of greatest risk is the early postoperative phase. Prophylactic beta-blockade significantly reduces perioperative cardiac morbidity and mortality: the odds ratio for myocardial ischaemia is 0.34 (95% CI: 0.23-0.52), for non-fatal myocardial infarction 0.15 (95% CI: 0.06-0.40) and for cardiac mortality 0.25 (95% CI: 0.09-0.73). Long-term continuation of the beta-blockade also reduces cardiac morbidity and mortality in the first two years following the operation.

A comparison between upfront high-dose tirofiban versus provisional use in the real-world of non-selected STEMI patients undergoing primary PCI: Insights from the Zwolle acute myocardial infarction registry.

BACKGROUND: Despite the proven benefit of glycoprotein IIb/IIIa blockers in patients with acute ST-segment elevation myocardial infarction (STEMI), there is still debate on the timing of administration of these drugs and whether all or only a selection of patients should be treated. We evaluated the effect of routine upfront versus provisional use of high-dose tirofiban (HDT) in a large real-world population of non-selected STEMI patients. METHODS: Consecutive STEMI patients were registered in a single-centre dedicated database. Patients with upfront HDT therapy before first balloon inflation were compared with patients who received the drug on a provisional basis, after first balloon inflation. Initial TIMI flow of the infarct-related vessel and enzymatic infarct size and 30-day clinical outcome were assessed. RESULTS: Out of 2679 primary PCI patients HDT was given upfront in 885 (33.0%) and provisionally in 812 (45.3%). Upfront as compared with provisional HDT showed higher initial patency (22.3 vs. 17.9%, p=0.006), smaller infarct size (1401 IU/l (IQR 609 to 2948) vs. 1620 (753 to 3132), p=0.03) and a lower incidence of death or recurrent MI at 30 days (3.3 vs. 5.1%, p=0.04) without an increase in TIMI bleeding (p=0.24). Upfront HDT independently predicted initial patency (odds ratio (OR) 1.47, 95% confidence interval (CI) 1.15 to 1.88, p=0.02), enzymatic infarct size (OR 0.70, 95% CI 0.56 to 0.86, p=0.001) and 30-day death or recurrent MI (OR 0.59, 95% CI 0.37 to 0.95, p=0.03). CONCLUSION: Our findings support the use of upfront potent antiplatelet and antithrombotic therapy in STEMI patients and encourage further clinical investigations in this field. (Neth Heart J 2010;18:592-7.).

Skin irritation by dithranol cream. A blind study to assess the role of the cream formulation.

In connection with a national cost-effective evaluation study of short contact dithranol therapy for psoriasis, the question arose whether dithranol cream irritation is influenced by constituents of the vehicle. To establish the role of the different components of the vehicle in the mechanism of dithranol irritation, the dithranol 3% cream used in the evaluation study and its vehicle with nine different combinations of its components were tested in a blind study. The creams were applied for 15, 30 and 45 min on the backs of 12 healthy volunteers. Irritation was scored as erythema by visual and colorimeter scoring. The dithranol creams with salicylic acid among their stabilizers showed 42% more irritation than the dithranol creams with only sorbic acid or no stabilizers at all. Stability tests showed no significant degradation of dithranol in the two less irritating creams when kept at 4 degrees C for 11 months. Salicylic acid in the cream aggravates dithranol-induced erythema.