European Society of Cardiology 2005: Round up

The gathering is a chance for scientists and researchers, as well as pharmaceutical and biotechnology companies from around the world to present the latest in scientific research to the attending cardiology community.

The meeting​, which is taking place in Stockholm, Sweden, was used to present Phase II data from Protein Design Labs, which suggested that its drug Ularitide holds promise as new treatment for acute decompensated heart failure.

When injected into the blood stream, ularitide causes relaxation of blood vessels, specifically in the arteries that feed the kidneys, lungs and heart, and stimulates natriuresis (excretion of abnormal amounts of sodium into the urine) and diuresis (increase in urination). These effects suggest a potential therapeutic role for ularitide in patients with Acute Decompensated Heart Failure (ADHF).

Ularitide is a synthetic form of urodilatin, which is a naturally occurring human protein that belongs to the family of natriuretic peptides and is produced in the kidney where it regulates levels of fluid and sodium.

Urodilatin is excreted into the urine and exists in low levels in the systemic blood circulation.

The data, which forms part of the SIRIUS II trial, consisted of a randomised, double blind, placebo-controlled clinical trial. A total of 221 patients were randomised equally to receive ularitide 7.5, 15, or 30 ng/kg/min given intravenously as a 24-hour infusion, or placebo.

Ularitide treatment was associated with a significantly improved dyspnea score in all three dosing groups compared to placebo. More patients reported moderate to marked improvement in dyspnea in all of the three treatment groups compared to placebo.

"The results of the SIRIUS II study show ularitide to be well-tolerated and indicate clear, dose-dependent favourable effects in treating the symptoms of ADHF without compromising kidney function,"​ said Veselin Mitrovic, medical director of the Research Unit / Kerckhoff Clinic, Bad Nauheim.

Meanwhile pharmaceutical giants, GlaxoSmithKline, used the meeting to announce headline results from the largest clinical trial ever conducted in patients with acute coronary syndromes (ACS).

The trials compared its new anti-thrombotic product, Arixtra (fondaparinux sodium) with the commonly used Lovenox/Clexane (enoxaparin). Arixtra was found to be as effective as Lovenox/Clexane for the primary composite endpoint of preventing death, myocardial infarction, and refractory ischaemia at 9 days (incidence of 5.9 per cent and 5.8 per cent, respectively); patients in the study experienced at least one of the three components of the primary endpoint.

Arixtra is the first in a new class of anti-thrombotics that selectively inhibits Factor Xa, a central protein in the coagulation process. In the treatment of thrombosis, Factor Xa plays a central role in the generation of thrombin, a protease in blood that facilitates blood clotting.

Arixtra has a proven safety profile with no reported cases of heparin-induced thrombocytopenia (HIT), a common and potentially fatal side effect of heparin.

Unstable chest pain and acute myocardial infarction caused by inadequate blood supply to the heart muscle are part of a complex group of cardiac diseases called ACS.

ACS affects approximately 3.5m people worldwide annually. People presented with these conditions have an increased immediate and long-term risk of recurrent heart attack and cardiac death.

"The findings demonstrate that Arixtra is likely an effective anti-thrombotic drug in many patients with ACS already receiving aspirin and clopidogrel,"​ said Dr. Salim Yusuf, principal investigator of the study, and professor of medicine, McMaster University and Hamilton Heath Sciences.

Two new therapies - one of which has been given the go-ahead by European Medical Evaluation Agency (EMEA) - for the treatment of coronary artery disease was announced by pharmaceutical company Servier at the meeting.

The ACE inhibitor Coversyl (perindopril) received a positive opinion from the EMEA recommending the extension of its licence indication for the treatment of patients with stable coronary artery disease (CAD) to reduce the risk of cardiac events in patients with a history of MI and / or revascularisation.

The FDA has now also approved a label extension for perindopril for a similar indication in the US. This new indication is in addition to Coversyl's position as an antihypertensive agent.

Servier also have a pipeline drug Procoralan (ivabradine), the first pure heart rate-lowering agent, which has also received positive EMEA feedback for the treatment of chronic stable angina in patients with normal sinus rhythm who have a contraindication or intolerance to beta-blockers.

Procoralan provides an important new approach to the management of angina. Unlike beta-blockers, the most common treatment for angina, Procoralan exclusively reduces heart rate and is therefore associated with fewer unwanted effects.

Heart rate reduction has been a therapeutic goal in angina treatment for many years. However, existing treatments do not exclusively reduce heart rate and their use is often associated with unwanted pharmacological actions and poor tolerability. In contrast, Procoralan exclusively reduces heart rate by a specific action on the sino-atrial node. It does not interfere with the contractility of the heart, atrioventricular conduction and ventricular repolarisation.

Encysive Pharmaceuticals presented Phase III trial data for Thelin, (sitaxsentan sodium), its small molecule that blocks the action of endothelin, a potent mediator of blood vessel constriction and growth of smooth muscle in vascular walls.

Endothelin receptor antagonists may prove to be effective in the treatment of a variety of diseases where the regulation of vascular constriction is important. Thelin is 6,500-fold selective in the targeting of the endothelin A receptor versus the endothelin B receptor.

The New Drug Application (NDA) for Thelin is now under active review by the Cardio- Renal Division of the FDA. The European Agency for the Evaluation of Medicinal Products is currently reviewing a Marketing Authorisation Application for approval of Thelin within the European Union.

Thelin will be used to treat pulmonary arterial hypertension (PAH) - a condition that involves high blood pressure and structural changes in the walls of the pulmonary arteries, which are the blood vessels that connect the right side of the heart to the lungs.

PAH causes shortness of breath, limits activity, and is eventually fatal unless treated successfully with heart/lung or lung transplantation. PAH is estimated to afflict approximately 100,000 to 200,000 people worldwide, many of whom are children and young women.