Hits and misses highlighted at ESC heart congress

The news from the European Society of Cardiology (ESC) meeting in Barcelona is currently being dominated by Novartis’ LCZ696 and Sanofi/Regeneron’s alirocumab, but there is a lot more going on to exercise the minds of cardiologists.

AstraZeneca has an early opportunity to trumpet its antiplatelet drug Brilinta/Brilique (ticagrelor), which has only just emerged from a US Department of Justice (DoJ) investigation into the PLATO trial which underpinned its approval in 2011.

The results of the ATLANTIC study show the drug is equally effective when given before hospital admission to heart attack patients as it is when given in hospital, in line with new ESC guidelines, with no adverse impact on bleeding rates. The results of the trial, which involved patients with ST segment elevation myocardial infarction (STEMI), suggest Brilinta can be given to patients at first medical contact as well as in hospital, making it a flexible option for patients undergoing life-saving percutaneous coronary interventions (PCIs) such as angioplasty.

Moreover, there was a hint in the results that early treatment with Brilinta in the ambulance could actually improve outcomes after PCI, which “warrants further investigation”, according to the company.

“Our study shows that there is no downside to earlier administration of ticagrelor, and it reduces the risk of post-procedure stent thrombosis which is a serious iatrogenic complication,” said lead investigator Gilles Montalescot of Pitié-Salpêtriėre Hospital, in Paris, France.

“It is also a more practical time point for administration of the drug than in the catheterisation laboratory, where considerable staff and technical demands already exist,” he added.

Pfizer and Bristol-Myers Squibb reported new data from the AMPLIFY-Extension trial of their oral anticoagulant Eliquis (apixaban), which indicate the drug significantly reduced hospitalisation rates compared to placebo over one year in patients with venous thromboembolism (VTE).

AMPLIFY-Ext was first unveiled at the end of 2012 and suggested that an extra year of treatment with the drug cuts the risk of recurrence of VTE, and the new data reinforces the value of that additional treatment duration, according to study investigator Alexander Cohen of King’s College London.

Eliquis benefits in reducing hospitalisation were independent of other factors such as renal function, which was the only other significant predictor of hospitalisation in the trial.

There was disappointment in the SIGNIFY trial of Servier and Amgen’s chronic heart failure drug ivabradine, however, after it failed to have any impact on cardiovascular events in patients with stable coronary artery disease (CAD).

As the drug acts mainly by lowering heart rate, the results call into question the idea that this is an effective treatment target in CAD patients without heart failure, say the researchers behind the trial. Ivabradine was able to reduce the heart rate by around 10 beats per minute in the 19,000-patient study, but there was no difference in the rate of cardiovascular death or nonfatal heart attack when compared to placebo.

The results also suggested worsening outcomes in patients with severe angina, a previously-reported finding that prompted the European Medicines Agency (EMA) to launch a re-assessment of the drug earlier this year. The dose used SIGNIFY is however higher than that approved for marketing in the EU.

Meanwhile, cardiologists got some insight into the failure of GlaxoSmithKline’s acute coronary syndrome (ACS) therapy darapladib with the first public discussion of the results of the SOLID-TIMI-52 trial.

ACS patients treated with darapladib alongside standard medical therapy did no better than those on medical therapy alone in the two-and-a-half-year study, which measured the combined rate of cardiovascular death, myocardial infarction and urgent cardiovascular revascularisation, according to the researchers behind the study.

The negative results – which came after darapladib also failed another trial called STABILITY in coronary artery disease patients, represent a setback for efforts to develop an anti-inflammatory treatment for atherosclerosis. GSK is undeterred however and recently started a large-scale trial of another anti-inflammatory drug, losmapimod, in ACS patients.

Biotechnology company Trophos also got some disappointing news after its experimental agent to prevent reperfusion injury in STEMI patients – TRO40303 – proved ineffective in the Phase I/IIb MITOCARE trial.

TRO40303 is designed to prevent tissue damage when impaired blood flow is corrected via PCI procedures but – like many other drugs developed for this use – was unable to show any positive effect on the size of the infarct.

Principal investigator Dan Atar of the University of Oslo in Norway described the findings as “yet another nail in the coffin” of reperfusion injury prevention.

Lifestyle changes

Finally, lest one forget that managing cardiovascular disease is not all about medal interventions, the ESC also provided interesting updates on the lifestyle changes we can all make to improve our health.

Studies reported in Barcelona indicated that drinking tea can cut blood pressure and reduce non-cardiovascular mortality (there was a trend towards reducing cardiovascular mortality as well), while it appears drinking wine only has a protective effect in those who exercise.

Avoiding energy drinks is likely a good idea though; a French study uncovered 257 cases in which the caffeine-laden drunks were linked to side effects, of which 95 involved cardiovascular symptoms.

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