Petr Widimský

Long distance transport for primary angioplasty vs immediate thrombolysis in acute myocardial infarction: Final results of the randomized national multicentre trial-PRAGUE-2

BACKGROUND Primary percutaneous coronary intervention (PCI) is shown to be the most effective reperfusion strategy in acute myocardial infarction. The aim of this multicentre national randomized mortality trial was to test whether the nationwide change in treatment guidelines (transportation of all patients to PCI centres) was warranted. METHODS The PRAGUE-2 study randomized 850 patients with acute ST elevation myocardial infarction presenting within <12 h to the nearest community hospital without a catheter laboratory to either thrombolysis in this hospital (TL group, n=421) or immediate transport for primary percutaneous coronary intervention (PCI group, n=429). The primary end-point was 30-day mortality. Secondary end-points were: death/reinfarction/stroke at 30 days (combined end-point) and 30-day mortality among patients treated within 0-3 h and 3-12 h after symptom onset. Maximum transport distance was 120 km. RESULTS Five complications (1.2%) occurred during the transport. Randomization-balloon time in the PCI group was 97+/-27 min, and randomization-needle time in the TL group was 12+/-10 min. Mortality at 30 days was 10.0% in the TL group compared to 6.8% mortality in the PCI group (P=0.12, intention-to-treat analysis). Mortality of 380 patients who actually underwent PCI was 6.0% vs 10.4% mortality in 424 patients who finally received TL (P<0.05). Among 299 patients randomized >3 h after the onset of symptoms, the mortality of the TL group reached 15.3% compared to 6% in the PCI group (P<0.02). Patients randomized within <3 h of symptom onset (n=551) had no difference in mortality whether treated by TL (7.4%) or transferred to PCI (7.3%). A combined end-point occurred in 15.2% of the TL group vs 8.4% of the PCI group (P<0.003). CONCLUSIONS Long distance transport from a community hospital to a tertiary PCI centre in the acute phase of AMI is safe. This strategy markedly decreases mortality in patients presenting >3 h after symptom onset. For patients presenting within <3 h of symptoms, TL results are similar results to long distance transport for PCI.

Effect of Platelet Inhibition with Cangrelor during PCI on Ischemic Events

BACKGROUND The intensity of antiplatelet therapy during percutaneous coronary intervention (PCI) is an important determinant of PCI-related ischemic complications. Cangrelor is a potent intravenous adenosine diphosphate (ADP)-receptor antagonist that acts rapidly and has quickly reversible effects. METHODS In a double-blind, placebo-controlled trial, we randomly assigned 11,145 patients who were undergoing either urgent or elective PCI and were receiving guideline-recommended therapy to receive a bolus and infusion of cangrelor or to receive a loading dose of 600 mg or 300 mg of clopidogrel. The primary efficacy end point was a composite of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 hours after randomization; the key secondary end point was stent thrombosis at 48 hours. The primary safety end point was severe bleeding at 48 hours. RESULTS The rate of the primary efficacy end point was 4.7% in the cangrelor group and 5.9% in the clopidogrel group (adjusted odds ratio with cangrelor, 0.78; 95% confidence interval [CI], 0.66 to 0.93; P=0.005). The rate of the primary safety end point was 0.16% in the cangrelor group and 0.11% in the clopidogrel group (odds ratio, 1.50; 95% CI, 0.53 to 4.22; P=0.44). Stent thrombosis developed in 0.8% of the patients in the cangrelor group and in 1.4% in the clopidogrel group (odds ratio, 0.62; 95% CI, 0.43 to 0.90; P=0.01). The rates of adverse events related to the study treatment were low in both groups, though transient dyspnea occurred significantly more frequently with cangrelor than with clopidogrel (1.2% vs. 0.3%). The benefit from cangrelor with respect to the primary end point was consistent across multiple prespecified subgroups. CONCLUSIONS Cangrelor significantly reduced the rate of ischemic events, including stent thrombosis, during PCI, with no significant increase in severe bleeding. (Funded by the Medicines Company; CHAMPION PHOENIX ClinicalTrials.gov number, NCT01156571.).

Long distance transport for primary angioplasty vs immediate thrombolysis in acute myocardial infarction

BACKGROUND Primary percutaneous coronary intervention (PCI) is shown to be the most effective reperfusion strategy in acute myocardial infarction. The aim of this multicentre national randomized mortality trial was to test whether the nationwide change in treatment guidelines (transportation of all patients to PCI centres) was warranted. METHODS The PRAGUE-2 study randomized 850 patients with acute ST elevation myocardial infarction presenting within <12 h to the nearest community hospital without a catheter laboratory to either thrombolysis in this hospital (TL group, n=421) or immediate transport for primary percutaneous coronary intervention (PCI group, n=429). The primary end-point was 30-day mortality. Secondary end-points were: death/reinfarction/stroke at 30 days (combined end-point) and 30-day mortality among patients treated within 0-3 h and 3-12 h after symptom onset. Maximum transport distance was 120 km. RESULTS Five complications (1.2%) occurred during the transport. Randomization-balloon time in the PCI group was 97+/-27 min, and randomization-needle time in the TL group was 12+/-10 min. Mortality at 30 days was 10.0% in the TL group compared to 6.8% mortality in the PCI group (P=0.12, intention-to-treat analysis). Mortality of 380 patients who actually underwent PCI was 6.0% vs 10.4% mortality in 424 patients who finally received TL (P<0.05). Among 299 patients randomized >3 h after the onset of symptoms, the mortality of the TL group reached 15.3% compared to 6% in the PCI group (P<0.02). Patients randomized within <3 h of symptom onset (n=551) had no difference in mortality whether treated by TL (7.4%) or transferred to PCI (7.3%). A combined end-point occurred in 15.2% of the TL group vs 8.4% of the PCI group (P<0.003). CONCLUSIONS Long distance transport from a community hospital to a tertiary PCI centre in the acute phase of AMI is safe. This strategy markedly decreases mortality in patients presenting >3 h after symptom onset. For patients presenting within <3 h of symptoms, TL results are similar results to long distance transport for PCI.

Blood pressure changes after renal denervation at 10 European expert centers

We did a subject-level meta-analysis of the changes (Δ) in blood pressure (BP) observed 3 and 6 months after renal denervation (RDN) at 10 European centers. Recruited patients (n=109; 46.8% women; mean age 58.2 years) had essential hypertension confirmed by ambulatory BP. From baseline to 6 months, treatment score declined slightly from 4.7 to 4.4 drugs per day. Systolic/diastolic BP fell by 17.6/7.1 mm Hg for office BP, and by 5.9/3.5, 6.2/3.4, and 4.4/2.5 mm Hg for 24-h, daytime and nighttime BP (P⩽0.03 for all). In 47 patients with 3- and 6-month ambulatory measurements, systolic BP did not change between these two time points (P⩾0.08). Normalization was a systolic BP of <140 mm Hg on office measurement or <130 mm Hg on 24-h monitoring and improvement was a fall of ⩾10 mm Hg, irrespective of measurement technique. For office BP, at 6 months, normalization, improvement or no decrease occurred in 22.9, 59.6 and 22.9% of patients, respectively; for 24-h BP, these proportions were 14.7, 31.2 and 34.9%, respectively. Higher baseline BP predicted greater BP fall at follow-up; higher baseline serum creatinine was associated with lower probability of improvement of 24-h BP (odds ratio for 20-μmol l−1 increase, 0.60; P=0.05) and higher probability of experiencing no BP decrease (OR, 1.66; P=0.01). In conclusion, BP responses to RDN include regression-to-the-mean and remain to be consolidated in randomized trials based on ambulatory BP monitoring. For now, RDN should remain the last resort in patients in whom all other ways to control BP failed, and it must be cautiously used in patients with renal impairment.

Randomized Comparison of Renal Denervation Versus Intensified Pharmacotherapy Including Spironolactone in True-Resistant Hypertension Six-Month Results From the Prague-15 Study

This prospective, randomized, open-label multicenter trial evaluated the efficacy of catheter-based renal denervation (Symplicity, Medtronic) versus intensified pharmacological treatment including spironolactone (if tolerated) in patients with true-resistant hypertension. This was confirmed by 24-hour ambulatory blood pressure monitoring after excluding secondary hypertension and confirmation of adherence to therapy by measurement of plasma antihypertensive drug levels before enrollment. One-hundred six patients were randomized to renal denervation (n=52), or intensified pharmacological treatment (n=54) with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4, respectively. A significant reduction in 24-hour average systolic blood pressure after 6 months (−8.6 [95% cofidence interval: −11.8, −5.3] mm Hg; P<0.001 in renal denervation versus −8.1 [95% cofidence interval: −12.7, −3.4] mm Hg; P=0.001 in pharmacological group) was observed, which was comparable in both groups. Similarly, a significant reduction in systolic office blood pressure (−12.4 [95% cofidence interval: −17.0, −7.8] mm Hg; P<0.001 in renal denervation versus −14.3 [95% cofidence interval: −19.7, −8.9] mm Hg; P<0.001 in pharmacological group) was present. Between-group differences in change were not significant. The average number of antihypertensive drugs used after 6 months was significantly higher in the pharmacological group (+0.3 drugs; P<0.001). A significant increase in serum creatinine and a parallel decrease of creatinine clearance were observed in the pharmacological group; between-group difference were borderline significant. The 6-month results of this study confirmed the safety of renal denervation. In conclusion, renal denervation achieved reduction of blood pressure comparable with intensified pharmacotherapy.

Clopidogrel pre-treatment in stable angina: for all patients >6 h before elective coronary angiography or only for angiographically selected patients a few minutes before PCI? A randomized multicentre trial PRAGUE-8

Aims To compare two different clopidogrel regimens on the outcomes of patients undergoing elective coronary angiography (CAG)±ad hoc percutaneous coronary intervention (PCI). Methods and results Open-trial randomized 1028 patients with stable angina to group A (‘non-selective’—clopidogrel 600 mg >6 h before CAG; n = 513) or group B (‘selective’—clopidogrel 600 mg in the cath-lab after CAG, only in case of PCI; n = 515). Combined primary endpoint was death/periprocedural myocardial infarction (MI)/stroke/re-intervention within 7 days. Secondary endpoints were troponin elevation and bleeding complications. Primary endpoint occurred in 0.8% group A patients vs. 1% group B (P = 0.749; 90% CI for the percentage difference −1.2–0.8). Periprocedural troponin elevation (>3× ULN) was detected in 2.6% group A vs. 3.3% group B (P = 0.475; 90% CI −2.5–1.0). Bleeding complications occurred in 3.5% group A patients vs. 1.4% group B (P = 0.025). After adjustment for covariates and factors that may influence the bleeding risk, patients in group A were shown to have more likely bleeding complications when compared with group B (OR = 3.03; 95% CI 1.14–8.10; P = 0.027). Conclusion High (600 mg) loading dose of clopidogrel before elective CAG increased the risk of minor bleeding complications, while the benefit on periprocedural infarction was not significant. Clopidogrel can be given safely in the catheterization laboratory between CAG and PCI in chronic stable angina patients.

Bioresorbable vascular scaffolds in acute ST-segment elevation myocardial infarction: a prospective multicentre study ‘Prague 19’

Aims Bioresorbable vascular scaffolds (BVSs) have been studied in chronic coronary artery disease, but not in acute ST-segment elevation myocardial infarction (STEMI). This prospective multicentre study analysed the feasibility and safety of BVS implantation during primary percutaneous coronary intervention (p-PCI) in STEMI. Methods and results Bioresorbable vascular scaffold implantation became the default strategy for all consecutive STEMI patients between 15 December 2012 and 30 August 2013. A total of 142 patients underwent p-PCI; 41 of them (28.9%) fulfilled the inclusion/exclusion criteria for BVS implantation. The BVS device success was 98%, thrombolysis in myocardial infarction 3 flow was restored in 95% of patients, and acute scaffold recoil was 9.7%. An optical coherence tomography (OCT) substudy (21 patients) demonstrated excellent procedural results with only a 1.1% rate of scaffold strut malapposition. Edge dissections were present in a 38% of patients, but were small and clinically silent. Reference vessel diameter measured by quantitative coronary angiography was significantly lower than that measured by OCT by 0.29 (±0.56) mm, P = 0.028. Clinical outcomes were compared between BVS group and Control group; the latter was formed by patients who had implanted metallic stent and were in Killip Class I or II. Combined clinical endpoint was defined as death, myocardial infarction, or target vessel revascularization. Event-free survival was the same in both groups; 95% for BVS and 93% for Control group, P = 0.674. Conclusion Bioresorbable vascular scaffold implantation in acute STEMI is feasible and safe. The procedural results evaluated by angiography and OCT are excellent. The early clinical results are encouraging.

Comparison of cardiac surgery with left atrial surgical ablation vs. cardiac surgery without atrial ablation in patients with coronary and/or valvular heart disease plus atrial fibrillation: final results of the PRAGUE-12 randomized multicentre study †

Aims Surgical ablation procedure can restore sinus rhythm (SR) in patients with atrial fibrillation (AF) undergoing cardiac surgery. However, it is not known whether it has any impact on long-term clinical outcomes. Methods and results This multicentre study randomized 224 patients with AF scheduled for valve and/or coronary surgery: group A (left atrial surgical ablation, n = 117) vs. group B (no ablation, n = 107). The primary efficacy outcome was the SR presence (without any AF episode) during a 24 h electrocardiogram (ECG) after 1 year. The primary safety outcome was the combined endpoint of death/myocardial infarction/stroke/renal failure at 30 days. A Holter-ECG after 1 year revealed SR in 60.2% of group A patients vs. 35.5% in group B (P = 0.002). The combined safety endpoint at 30 days occurred in 10.3% (group A) vs. 14.7% (group B, P = 0.411). All-cause 1-year mortality was 16.2% (A) vs. 17.4% (B, P = 0.800). Stroke occurred in 2.7% (A) vs. 4.3% (B) patients (P = 0.319). No difference (A vs. B) in SR was found among patients with paroxysmal (61.9 vs. 58.3%) or persistent (72 vs. 50%) AF, but ablation significantly increased SR prevalence in patients with longstanding persistent AF (53.2 vs. 13.9%, P < 0.001). Conclusion Surgical ablation improves the likelihood of SR presence post-operatively without increasing peri-operative complications. However, the higher prevalence of SR did not translate to improved clinical outcomes at 1 year. Further follow-ups (e.g. 5-year) are warranted to show any potential clinical benefit which might occur later.

2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation

2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation

Meta-analysis of randomized controlled trials of renal denervation in treatment-resistant hypertension

Abstract Objective. The blood pressure (BP)-lowering effect of renal sympathetic nervous denervation (RDN) in resistant hypertension (rHT) shows large variation among studies. Methods. We meta-analyzed summary statistics of randomized clinical trials on RDN in rHT. For continuous outcomes, we assessed heterogeneity by Cochrans Q test and used random-effect models weighted for the inverse of the variance. We assessed safety by assessing the risk of major adverse events from stratified contingency tables. Results. Of 5652 patients screened in seven trials, 985 (17.4%) qualified and were randomized to control (n = 397) or RDN with SYMPLICITY™ catheters (n = 588). Follow-up was 6 months. In both control and RDN patients, antihypertensive treatment was continued or optimized. At enrolment, age averaged 58.1 years, systolic/diastolic office and 24 h BP 168.5/93.3 mmHg and 151.8/86.1 mmHg, respectively, and estimated glomerular filtration rate (eGFR) 79.3 ml/min/1.73 m². For BP outcomes, there was heterogeneity among trials. Pooled effects (control minus RDN) were −4.9/−3.5 mmHg (95% confidence interval, −20.9 to 11.1/−8.9 to 1.9) for office BP, −2.8/−1.5 mmHg (−6.5 to 0.8/−3.3 to 0.4) for 24 h BP and 0.81 ml/min/1.73 m² (−1.69 to 3.30) for eGFR. Removing one trial at a time produced confirmatory results. Adverse events occurred in 7.4% and 9.9% of control and RDN patients, respectively (p = 0.24). Conclusion. In selected rHT patients maintained on antihypertensive drugs, RDN with the SYMPLICITY systems does not significantly decrease BP but is safe. Future trials with next-generation catheters should aim at identifying responders in patients with evidence of sympathetic nervous overactivity.