Abstrakt
In the previous article, we described how the 'PRAGUE"' Trials series started and the first two studies dealt with ST-segment elevation myocardial infarction (STEMI). A short description of the most important subsequent trials is presented below.
There are now 21 (per end 2016) original academic clinical trials dealing with different topics in cardiology and cardiac surgery from the Czech Republic. After a small prematurely terminated PRAGUE-3 trial (primary percutaneous coronary intervention (PCI) in STEMI late-comers), we decided to expand our activities beyond STEMI-to also include cardiac surgery.
The leader of all cardiac surgery PRAGUE trials is Prof. Zbynek Straka.
The PRAGUE-4 trial was a cardiac surgery trial comparing off-pump (beating heart) coronary artery bypass graft (CABG) vs. classic CABG performed with extracorporeal circulation (on-pump, cardiac arrest during the surgery). Off-pump technique was applicable in 85% of patients and was at least as clinically safe and effective as on-pump surgery.
The patency of arterial coronary bypass grafts inserted on the beating heart was excellent and similar to grafts performed on-pump.1,2 PRAGUE-5 (led by Dr Radovan Jirmar) was another small trial testing very early (24 h) discharge after uncomplicated STEMI treated by primary PCI. PRAGUE-6 was a continuation of PRAGUE-4 focused on patients with a Euroscore greater than 6 points.
PRAGUE-7 was another small trial testing the use of abciximab in cardiogenic shock (co-ordinated by Dr Petr Tousek). As we did not believe in routine clopidogrel pre-treatment before any coronary angiography (CAG), which was routine in most centres at that time, we designed the study PRAGUE-8.
The study population was the largest of the PRAGUE trials until that time (n = 1028). Patients were randomized to either pre-treatment with non-selective use of clopidogrel 600 mg > 6 h before every CAG or selective use of clopidogrel 600 mg in the cath-lab after CAG, only in case of PCI.
The high loading dose of clopidogrel before elective CAG increased the risk of minor bleeding complications, while the benefit on peri-procedural infarction was not significant. The study confirmed our practice at that time, that clopidogrel given in the catheterization laboratory between CAG and PCI was safe.3 The PRAGUE-9 study was a very ambitious study prepared jointly by cardiologists and cardiac surgeons from several Czech tertiary centres.
Patients with coronary artery disease suitable for revascularization + mitral regurgitation (known to have significant mortality and morbidity after surgery) were randomized to either complete surgical treatment (CABG + mitral valve repair) or just PCI leaving the mitral valve untouched. Unfortunately, this study was terminated due to extremely slow recruitment-patients did not agree with randomization in this setting.
Some patients preferred PCI, while others preferred surgery. PRAGUE-10 and -11 were small studies with limited impact.
The PRAGUE-12 study was investigating the role of surgical treatment of atrial fibrillation added to elective CABG or valve surgery. In the control group just the main disease (coronary arteries and/or valves) were treated without atrial ablation.
Surgical ablation improved the likelihood of sinus rhythm post-operatively without increasing peri-operative complications. However, this did not translate to improved clinical outcomes at 1 year.4 The PRAGUE-13 study was testing the optimal treatment strategy for multivessel disease in STEMI: multivessel PCI vs. only PCI of infarct artery.
This small trial found no difference (not even a trend) favouring staged multivessel PCI over culprit-only primary PCI in STEMI. PRAGUE-14 was a registry analysing bleeding and ischaemic complications in cardiac patients undergoing non-cardiac surgery.
Peri-operative cardiovascular complications in these high-risk elderly all-comer surgical patients with known cardiovascular disease were relatively rare, but once they occurred, the mortality was high. Peri-operative bleeding complications were more frequent, but their case fatality was extremely low.
Patterns of interruption of chronic aspirin therapy before major non-cardiac surgery were not predictive for peri-operative complications (neither cardiovascular, nor bleeding). Simple baseline clinical factors are better predictors of outcomes than antithrombotic drug interruption patterns.5 The PRAGUE-15 study was the 2nd largest randomized study on the role of renal denervation in resistant hypertension.
Catheter-based renal denervation (in addition to maximal pharmacologic therapy) was compared with adding spironolactone to previous maximal pharmacotherapy. The result was neutral (no benefit from renal denervation).6 The PRAGUE-16 study is an ongoing registry collecting data on acute stroke interventions aiming to investigate two questions: (i) feasibility/safety of catheter-based interventions for acute ischaemic stroke performed in close cooperation of cardiologists, neurologists, and radiologists, (ii) outcomes of patients treated by direct catheter-based thrombectomy (without bridging thrombolysis).7 The PRAGUE-17 study is an ongoing national multicentre project comparing percutaneous closure of the left atrial appendage vs. best medical treatment (novel oral anticoagulants) in patients at high risk of stroke and increased risk of bleeding.
The study is enrolling patients and is expected to present the first results within 2-3 years. The PRAGUE-18 study was recently presented in the Hot Line session at the ESC Congress 2016 and published in Circulation.8 The study compared prasugrel vs. ticagrelor in STEMI and found that both antiplatelet drugs are similarly effective and safe.
The PRAGUE-19 study was a registry testing the feasibility and safety of bioresorbable vascular scaffolds in patients with acute STEMI.9 Three additional PRAGUE trials are currently ongoing and another one is planned. The entire large team of investigators, from nearly all tertiary cardiology centres in the Czech Republic as well as from many smaller hospitals and participating physicians and nurses are proud of this unique series of purely academic trials.
Most of these trials received minimal funding and have only been completed thanks to the great enthusiasm of numerous colleagues. The enthusiasm and friendship of the broad multicentre PRAGUE trials team is best illustrated by two recent photographs.
Figure 1 was taken in Charles University Aula Magna in Prague and some of the investigators had to travel 200-400 km to Prague just to participate in this picture. Figure 2 was taken in Rome on the evening after the 'PRAGUE-18' study was presented in the ESC Hot Line session and published in Circulation.