ESC Congress 2015, London: hot lines truly hot?
ESC Congress 2015, London: hot lines truly hot?
E.E. van der Wall 0
0 E.E. van der Wall () Netherlands Society of Cardiology, Holland Heart House , Moreelsepark 1, 3511 EP Utrecht , The Netherlands
At the ESC Congress 2015 in London, six different Hot Line sessions were organised. The six topics were acute myocardial infarction, atrial fibrillation/pacing, diabetes/pharmacology, hypertension, heart failure, and coronary artery disease. Hot Line sessions are usually the main attraction of the ESC Congress as novel data are being presented for the first time . Altogether 26 novel studies were presented during the six Hot Line sessions. All these Hot Line studies will be reported in detail in a special NHJ supplement that is added to this November edition of our journal. Therefore, the outcomes of all these trials will not be addressed here. The focus of this Comment is to briefly highlight those trials that had a negative (or neutral) outcome. Over the past years, trials with a negative outcome seem to outnumber trials with a positive outcome during the annual ESC Congresses [2, 3]. The following studies mentioned below had a negative outcome for their primary endpoints at the ESC Congress 2015 in London.
1. The CIRCUS (Does Cyclosporine Improve Clinical
Outcome in ST-elevation Myocardial Infarction
Patients?) trial failed to show that cyclosporine improved
clinical outcomes or prevented adverse left ventricular
remodelling in anterior ST-segment elevation
myocardial infarction (STEMI). The goal of the trial was to
evaluate treatment with cyclosporine compared with placebo
among subjects undergoing primary percutaneous
coronary intervention for anterior STEMI.
2. The ALBATROSS (Aldosterone Lethal Effects Block
ade in Acute Myocardial Infarction Treated With or
Without Reperfusion to Improve Outcome and Survival
at Six Months Follow-up) trial failed to show that
aldosterone antagonists were beneficial to patients with
myocardial infarction without heart failure.
3. The PRomPT (Post-Myocardial Infarction Remodelling
Prevention Therapy) trial showed that peri-infarct
pacing did not prevent left ventricular remodelling or
improve functional, or clinical outcomes during 18 months
of follow-up in patients with a large first myocardial
4. The OPTIDUAL (Optimal Duration of Dual Antiplate
let Therapy After Drug-eluting Stent Implantation) trial
aimed to evaluate dual antiplatelet therapy (DAPT) for
an additional 36 months among subjects who received
a drug-eluting stent and were event-free at 12 months.
The trial failed to reach primary outcome; however,
extended duration of DAPT non-significantly reduced
ischaemic events without increasing bleeding.
5. The ARTS-HF (Mineralocorticoid Receptor AnTagonist
Study In Heart Failure) trial failed to show a reduction
in NT-proBNP levels for finerenone versus eplerenone;
however, secondary outcomes favoured finerenone.
6. The TECOS (Trial Evaluating Cardiovascular Out
comes with Sitagliptin) trial showed that sitagliptin
improves glycaemic control without increasing adverse
cardiovascular events. Among diabetic subjects with
documented cardiovascular disease, sitagliptin was
noninferior to placebo on the outcome of adverse
7. The ELIXA (Evaluation of Lixisenatide in Acute Coro
nary Syndrome) study evaluated treatment with
lixisenatide versus placebo in patients with type 2 diabetes
presenting with an acute coronary syndrome. Although
lixisenatide showed significant changes in biomarkers,
a neutral effect upon cardiovascular death, myocardial
infarction and stroke was found.
8. The SCOT (Standard Care versus Celecoxib Outcome
Trial) showed that adverse cardiovascular event rates
were similar between celecoxib and nonselective
nonsteroidal anti-inflammatory drugs (NSAID). The goal of
the trial was to evaluate treatment with celecoxib
compared with a nonselective NSAID among subjects with
arthritis and no known cardiovascular disease.
9. The MATRIX (Minimizing Adverse Hemorrhagic
Events by Transradial Access Site and Systemic
Implementation of AngioX) trial showed that bivalirudin did
not reduce major or net adverse events versus heparin;
however, bleeding/death was reduced and stent
thrombosis increased. Several lines of evidence even suggest
an increased risk of stent thrombosis with bivalirudin.
10. The BENEFIT (BENznidazole Evaluation For
Interrupting Trypanosomiasis) study showed that
benznidazole did not reduce progression of Chagas disease
cardiomyopathy among patients with Chagas disease.
However, it was found that a 40–80 day treatment with
this antiparasitic medication significantly reduced
parasitic activity in the blood.
11. The UNDER-ATP (Atrial Fibrillation/Pacing Adenosine
Triphosphate) trial showed that guided pulmonary vein
isolation in comparison to conventional pulmonary vein
isolation did not reduce late recurrence atrial fibrillation
at 1 year follow-up.
12. The PRESERVATION I showed that a novel
Bioabsorbable Cardiac Matrix (BCM) is safe but does not benefit
STEMI patients with large infarcts; it does not prevent
left ventricular remodelling or other adverse outcomes.
13. The ‘Optimization of Heart Failure Management Using
Medtronic OptiVol Fluid Status Monitoring and
CareLink Network’ (OptiLink) study assessed the effect of
intrathoracic impedance monitoring, through automatic
wireless telemedicine notification on all-cause death and
cardiovascular hospitalization. The primary composite
endpoint did not differ between the two groups
(telemedicine guided system or controls).
14. The ‘Calcium Up-Regulation by Percutaneous
Administration of Gene Therapy in Cardiac Disease Phase 2b’
(CUPID2) trial, investigating the efficacy and safety of
intracoronary administration of adeno-associated virus
type I (AAV1)/SERCA2a in patients with advanced
heart failure, showed that treatment with
AAV1/SERCA2a was safe but failed to improve the rate of
recurrent events as well as the time to the first terminal event.
15. The ‘Treatment of Sleep-Disordered Breathing with
Predominant Central Apnoea with Adaptive
Servo-Ventilation in Patients with Chronic Heart Failure’
(SERVEHF) showed that the composite primary endpoint (time
to first event of all-cause death, life-saving intervention,
or unplanned hospitalization for chronic heart failure)
did not differ between intervention and control group.
In fact, all-cause death and cardiovascular death were
elevated in the treatment arm.
At a first glance the ‘negative’ outcomes of these trials
seem rather disappointing. One could therefore really
wonder whether all Hot Line studies were truly hot. However,
it should be realised that the label ‘positive’ or ‘negative’
hinges on a p-value of < 0.05 or > 0.05; this might in
principle have nothing to do with the clinical implication of a
study, be it positive or negative. Secondly, ‘negative’
usually only applies to the primary endpoint; in some instances
the drugs studied in the above-mentioned trials showed
improved safety beyond the neutral finding. Finally, the
ultimate proof of the value of a large clinical study is
incorporation into the guidelines [4–8].
Nevertheless, there is a flipside of the coin. Sometimes one
cannot escape the feeling that also in science there is a l’art
pour l’art approach; are all the above-described studies really
needed? Are the studies truly hypothesis-driven? Will the
outcome of the study change the treatment policy for the
individual patient? Finally, will it impact the existing guidelines [9,
10]? Therefore, the impression occasionally arises that some
studies are primarily performed for the sake of the industry,
followed by the urge of the researchers, and lastly in the
interest of the patient. I sincerely hope this impression is false.
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1. van der Wall EE . ESC Congress 2008 in Munich: hot news from hot lines! Neth Heart J . 2008 ; 16 : 367 - 8 .
2. Fox KA . What's new for ESC Congress 2013 ? (Amsterdam 30 August-4 September 2013 ). Neth Heart J . 2013 ; 21 : 304 - 6 . doi:10.1007/s12471- 013 - 0419 -6.
3. van der Wall EE . Main results of the ESC Congress 2013 , Amsterdam: moving or standstill in cardiology? Neth Heart J . 2013 ; 21 : 477 - 9 . doi: 10.1007/s12471- 013 - 0477 -9.
4. Wijers SC , van der Kolk BY , Tuinenburg AE , Doevendans PA , Vos MA , Meine M. Implementation of guidelines for implantable cardioverter-defibrillator therapy in clinical practice: which patients do benefit? Neth Heart J . 2013 ; 21 : 274 - 83 . doi:10.1007/ s12471- 013 - 0407 -x.
5. Verheugt FW . Trials, registries and guidelines for non-ST-elevation acute coronary syndromes . Neth Heart J . 2014 ; 22 : 52 - 4 . doi:10.1007/s12471- 013 - 0495 -7.
6. Tra J , van der Wulp I , Appelman Y , de Bruijne MC , Wagner C. Adherence to guidelines for the prescription of secondary prevention medication at hospital discharge after acute coronary syndrome: a multicentre study . Neth Heart J . 2015 ; 23 : 214 - 21 . doi:10.1007/ s12471- 015 - 0664 -y.
7. Verheugt FW . Anticoagulation in patients with mechanical heart valves: follow the guidelines ! Neth Heart J . 2015 ; 23 : 109 - 10 . doi:10.1007/s12471- 014 - 0642 -9.
8. van der Wall EE . New ESC guidelines on hypertrophic cardiomyopathy: new insights in invasive treatment? Neth Heart J . 2015 ; 23 : 1 - 3 . doi:10.1007/s12471- 014 - 0636 -7.
9. Claessen BE , van der Schaaf R , Cate TT , Piek JJ. A Dutch perspective on the ESC/EACTS guidelines on myocardial revascularisation . Neth Heart J . 2015 ; 23 : 290 - 1 . doi:10.1007/ s12471- 015 - 0685 -6.
10. de Boer MJ , van der Wall EE . Choosing wisely or beyond the guidelines . Neth Heart J . 2013 ; 21 : 1 - 2 . doi:10.1007/s12471- 012 - 0352 -0.