European Society of Cardiology (ESC) Congress 2014

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he ESC Congress 2014 was one of the largest meetings in the history of the society, with more than 30,300 delegates in attendance at 27 clinical Hot Line presentations; 15 clinical trial updates; 19 registry studies; 4 new guidelines; and 4597 abstracts presented. Cardiology Review profiles 7 presentations.

PARADIGM-HF: Excitement Over Investigational HF Med

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new investigational Novartis medication (LCZ696) studied in the PARADIGM-HF trial garnered a great deal of attention after results of this large study showed that the drug performed better than enalapril at decreasing cardiovascular mortality in patients with chronic HF.

John JV McMurray, MD, and colleagues compared the angiotensin-neprilysin inhibitor LCZ696 with enalapril in patients who had HF with a reduced ejection fraction to determine if the long-term effects of LCZ696 on morbidity and mortality were superior to those of ACE inhibition with enalapril. LCZ696 contains moieties of valsartan and sacubitril and is classified as an angiotensin receptor-neprilysin inhibitor (ARNI). Their study was published in The New England Journal of Medicine (2014;371:993-1004).

PARADIGM-HF randomized more than 8000 patients with depressed left ventricular systolic function, almost all of whom were in NYHA Class II to III, to treatment with LCZ696 or enalapril in addition to other evidence-based therapies.

Patients who received LCZ696 showed a 20% decrease in deaths or HF hospitalizations as a lone end point (P<.001 for both) over 2 to 3 years compared with enalapril. All-cause mortality fell 0.80% (P<.0010).

Study co-author Milton Packer, MD, who presented the trial, said the magnitude of the advantage of LCZ696 over enalapril on cardiovascular mortality was at least as large as that of enalapril over placebo during long-term treatment in the early trials. “LCZ696 effectively doubled the survival benefit of enalapril,” he noted. “This robust finding provides strong support for using LCZ696 instead of ACE inhibitors or angiotensin-receptor blockers in the treatment of chronic heart failure.”

Pre-Hospital vs In-Hospital Ticagrelor in STEMI Patients

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tent thrombosis rates were significantly reduced at 24 hours and at 30 days among patients who were given ticagrelor (Brilinta) in the ambulance en route to hospitals able to provide percutaneous coronary intervention (PCI). Although safe, ticagrelor did not improve pre-PCI coronary perfusion compared with in-hospital administration of ticagrelor, according to ATLANTIC investigator Gilles Montalescot, MD, PhD, of Centre Hospitalier University Pitié-Salpêtrière, Paris. Dr Montalescot said bleeding rates were no different between the group that got ticagrelor in the ambulance and the group that received it in the hospital.

ATLANTIC enrolled 1870 STEMI patients who were first managed by ambulance physicians who determined that the patients needed primary PCI. Patients were then randomized to placebo loading dose and given a ticagrelor loading dose of 180 mg when they arrived at the PCI hospital, or they were given 180 mg ticagrelor during ambulance transfer.

For both of the study’s co-primary end points (no ST-segment resolution ≥70% and no TIMI 3 flow in the infarct-related artery), there were no differences between the 2 treatment methods. With the exception of patients who did not receive morphine for the index PCI, this was also true for subgroups including myocardial infarction (MI) location, Killip classification, and GPIIb/IIIa use prior to angiography. Patients who did not receive morphine benefited from pre-hospital administration of ticagrelor.

MACE Risk Lower in STEMI Patients With Complete Vascularization

Following in the footsteps of the 2013 PRAMI trial—the first randomized controlled trial to show a dramatic benefit for complete vascularization versus infarct-related artery (IRA) revascularization at time of index admission&mdash;the Complete Versus Lesion-Only Primary PCI Trial (CvLPRIT) findings suggest that complete revascularization at index admission led to a larger reduction in major adverse cardiac events (MACE) at 12 months than IRA revascularization. The findings are a departure from European and US guidelines, which support a more gradual approach to primary PCI.

Calculated by time to first event, the 12-month risk of MACE was 55% lower in the complete revascularization group.

Investigator Anthony Gershlick, MD, of University Hospitals of Leicester, UK, said the difference becomes apparent within the first month, suggesting that staged PCI could be risky. He said that reduction in MACE was not solely because of a reduction in later PCI but also because of fewer deaths, recurrent MI, and HF.

In CvLPRIT 297, STEMI patients presenting at 7 UK centers were randomized to receive revascularization that was infarct-only (n = 146) or complete (n = 150). In the latter group, the infarct-related artery underwent PCI first before treatment of any significantly blocked non-infarct-related arteries, ideally within the same procedure but at least during the index hospitalization.

A total of 139 patients received treatment of the IRA only; 7 crossed over to complete revascularization. In the complete vascularization arm, 139 patients had all eligible vessels treated, 8 patients ultimately had treatment of the culprit vessel only, and an additional 3 received IRA treatment only plus referral for bypass.

Dr Gershlick said the results of CvLPRIT suggest that this strategy may need to be considered by future STEMI guidelines committees.

Alirocumab Reduced LDL Cholesterol Significantly

lirocumab, Sanofi/Regeneron’s investigational proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, significantly reduced low-density lipoprotein (LDL) cholesterol in different groups of patients participating in the ODYSSEY trial, including people at high risk for cardiovascular events currently taking a maximally tolerated statin dose.

The ODYSSEY Long-Term Study consisted of 2341 patients at high risk for cardiovascular events. Researchers conducted a post hoc study to investigate the effect of alirocumab on major cardiovascular events. This was the same end point tested in the major morbidity and mortality ODYSSEY OUTCOMES study. After 65 weeks of treatment with alirocumab, the drug was found to significantly reduce the risk of major events compared with those who received placebo and a maximally tolerated statin.

Lead investigator of the long-term ODYSSEY study, Jennifer Robinson, MD, of the University of Iowa, Iowa City, said that while the post hoc analysis should be interpreted with caution, the data suggest researchers are on the right track with alirocumab.

No Effect Overall Adding Ivabradine in Stable CAD

The results of the SIGNIFY (Study Assessing the Morbidity-Mortality Benefits of the If Inhibitor ivabradine in Patients with Coronary Artery Disease) trial suggest that adding ivabradine (Procoralan) to standard therapy had no effect overall on cardiovascular events in a placebo-controlled trial of 19,000 patients with stable CAD. The results were published in The New England Journal of Medicine (2014;371:1091-1099).

Treatment with ivabradine was associated with an average drop in heart rate of 10 beats per minute compared with placebo, measured after the third month of the trial. Over a mean of approximately 28 months, 6.8% of ivabradine patients and 6.4% of patients given placebo met the primary end point of cardiovascular death or nonfatal MI. Lead study author Kim Fox, MD, of Imperial College, London, UK, said that the results suggest that an elevated heart rate is only a marker of risk, not a modifiable determinant of outcomes, in patients with stable CAD without clinical HF.

An additional analysis of data from SIGNIFY found that ivabradine was associated with significantly worse outcomes in a subgroup of patients that made up more than half the study population: those with angina of at least Canadian Cardiovascular Society (CCS) class 2.

SOLID-TIMI 52 Shows No Benefit for Darapladib

Patients with acute coronary syndrome (ACS) who took darapladib, a selective inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2), in addition to optimal medical therapy, did not do any better than ACS patients receiving optimal medical therapy alone, according to investigators presenting the results ofSOLID-TIMI 52.

SOLID-TIMI 52 followed 13,026 patients stabilized following an ACS event. They were ran&shy;domized to placebo or darapladib.

Darapladib failed to reduce the risk of heart disease, MI, and urgent coronary revascularization compared with placebo during a median follow-up of 2.5 years. Treatment with darapladib failed to positively affect any cardiovascular end point. Michelle O’Donoghue, MD, of Brigham and Women’s Hospital, Boston, said the results do not support a strategy of targeted Lp-PLA2 inhibi&shy;tion with darapladib in patients stabilized after an ACS event who are similar to those enrolled in this trial.

Vagal Nerve Stimulation Fails to Improve LVESD in HF Patients

An investigational procedure that was hoped to enhance parasympathetic tone by direct stimulation of the vagal nerve failed to improve left ventricular end-systolic diameter (LVESD) in HF patients with low ejection fractions in the NECTAR-HF (Neutral Cardiac Therapy for Heart Failure) study.

It had been hypothesized that vagal nerve stimulation could normalize autonomic imbalances in HF patients and prevent the progression of disease. An earlier pilot study showed improvements following vagal nerve stimulation, but that study had not included a sham-treated control group.

The vagal nerve stimulation also did not have an effect on other echocardiographic measure&shy;ments of cardiac remodeling such as left ventricular end-diastolic diameter, left ventricular end-systolic and diastolic volumes, and left ventricular ejection fraction. Nor was there any improvement in exercise capacity or N-terminal probrain natriuretic peptide levels.

In NECTAR-HF, 96 patients were randomized 2:1 to either vagal-nerve stimulation or a sham procedure. At 6 months there was no significant improvement in any of measure of cardiac re&shy;modeling or functional capacity. However, quality of life measurements and NYHA functional class were significantly improved with the vagal nerve stimulation. Investigators suggest that quality-of-life and functional class measures should be interpreted with caution because of their subjective nature and negative trial results and difficulties with adequate blinding of subjects to the sham procedure.