The European Society of Cardiology (ESC) 2015 Congress was held in London, United Kingdom from August 29-September 2, 2015.

Notable presentations this year were in dyslipidemia, looking at the implications of subgroup analyses from Vytorin's (MRK) IMPROVE-IT and potential competition in the PCSK9 space from ALN-PCSsc (MDCO, ALNY). Though a latecomer, the latter could turn out to have an appreciable dosing advantage over earlier options. Bayer's finerenone also had interesting Phase IIb data in heart failure.

In the device space, St. Jude's Nanostim leadless pacemaker had IDE data, though some questions on complications were raised. There were also notable failed trials for Medtronic's Optivol and Resmed's adaptive servo-ventilation in heart failure patients.

CONFERENCE HIGHLIGHTS

Dyslipidemia

• Analyses from Vytorin's (MRK, ezetimibe+simvastatin) IMPROVE-IT found an appreciably larger effect in diabetics and certain other very high risk groups. While some data on this has been seen already and there is caution about such analyses, some experts are now raising more questions whether ezetimibe may primarily be suited to certain subgroups. Still, the results in diabetics were encouraging.
  • More data on a risk score and other subgroups is to be presented at the AHA conference in November.
  • Implications for other drugs depend on whether the findings are related to the more modest LDL-c reduction of ezetimibe or effects of drugs added to statins when LDL-c is fairly well controlled.
• In a Phase I study, the PCSK9 inhibitor ALN-PCSsc (MDCO, ALNY) demonstrated the potential for quarterly or possibly semi-annual dosing with a favorable injection volume.
  • The 300mg dose favored by the company did have some earlier waning of effect on LDL-c in combination with statins, but since PCSK9 knockdown did not change, it is unclear if that was just due to variability in a small study.

Heart Failure

• Mineralocorticoid anatagonist finerenone (BAYRY) missed its primary outcome effect on NTP-proBNP in a Phase IIb trial against eplerenone. However, all except the lowest dose had better clinical outcomes, prompting the company to advance it to Phase III.
  • Those dose groups also had lower NT-proBNP at baseline, complicating interpretation.
  • There were only modest suggestions of a benefit on hyperkalemia.
  • The Phase IIb trial in diabetic nephropathy was also published concurrently with the conference. The clear dose-dependent reduction in UACR was reiterated, without any surprises on safety.
    • Rates of discontinuation for hyperkalemia were not high, but it is difficult to compare efficacy and safety to current options without a direct comparison. Still, finerenone will have the advantage that other drugs have not been studied as well in this indication.
• Optivol, a feature of Medtronic ICD/CRT devices that assesses fluid status through impedance, failed to show a benefit on clinical outcomes in the OPTILINK HF trial.
• Resmed's adaptive servo-ventilation appreciably increased mortality in a trial of heart failure patients with central sleep apnea. Thus far, results are only thought to apply to central sleep apnea. More information may come from trials of Respicardia's remede phrenic-nerve stimulation and Philips Respironics ASV device.

Dysrhythmia

• The Nanostim (STJ) leadless pacemaker met performance goals in an IDE study. However, there are still questions about long- term use and some had concerns about the rate of cardiac perforations in particular. A leadless proponent said more experience and better selection of the location of implantation could help.
  • Such devices are currently for the single chamber segment of the market, which may account for 15-25% of pacemakers, but companies are working on dual chamber devices.

Acute Coronary Syndrome and Coronary Artery Disease

• An analysis from Brilinta's (AZN, MDCO) PEGASUS study argued against starting the drug in prior heart attack patients who have already been on aspirin monotherapy a year without further events.
• In the first RCT for Absorb (ABT) in STEMI patients, the bioresorbable scaffold stent demonstrated non-inferiority to Xience on a healing score, with a trend for superiority. The discussant speculated that the thicker struts, while leading to some increased late lumen loss, allows more complete healing.
  • Met endpoint in pivotal Japan registration trial, as well.

Cardiovascular Safety of Diabetes Drugs

• Further analyses from Januvia's (MRK) TECOS cardiovascular outcomes trial further confirmed the lack of an increase in hospitalization for heart failure (HHF) or related outcomes.

The report includes data from other drugs and devices, as well.

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