By: Bruce Sylvester

STOCKHOLM, SWEDEN – Investigative ticagrelor is a more effective treatment for acute coronary syndromes than clopidogrel, regardless of CYP2C19 and ABCB1 polymorphisms, according to a new genetic substudy reported at the European Society of Cardiology Congress 2010. The study was published simultaneously online by The Lancet.

“Our findings indicate that use of ticagrelor instead of clopidogrel eliminates the need for currently recommended genetic testing before dual-antiplatelet treatment,” said Lars Wallentin, MD, Uppsala University, Uppsala, Sweden.

The investigators evaluated the effects of CYP2C19 and ABCB1 on the efficacy and safety of ticagrelor and clopidogrel. CYP2C19 and ABCB1 have been shown to affect the efficacy of clopidogrel.

In the Study of Platelet Inhibition and Patient Outcomes (PLATO) trial, 18,624 patients with acute coronary syndrome were randomised to ticagrelor 180 mg loading dose and 90 mg twice-daily maintenance dose vs clopidogrel 300 to 600 mg loading dose and 75 mg daily maintenance dose for 6 to 12 months (median 9 months). All patients received background aspirin therapy.

For this substudy, the investigators genotyped 10,285 DNA samples from PLATO subjects for CYP2C19 loss-of-function and gain-of-function alleles and for an ABCB1 nucleotide polymorphism. Patients were stratified according to the presence or absence of any loss-of-function CYP2C19 allele and for predicted high, medium, or low expression of ABCB1. The primary efficacy endpoint was cardiovascular death, myocardial infarction, or stroke after up to 12 months of treatment with ticagrelor or clopidogrel.

Primary outcome events occurred less often with ticagrelor than with clopidogrel, regardless of CYP2C19 genotype: 8.6% vs 11.2% in patients with any loss-of-function CYP2C19 variation (P =.038) and 8.8% vs 10.0% in those without any variation (P =.0608).

For ABCB1 groups (low, intermediate, and high expression), ticagrelor event rates (8.1% to 9.0% per year) were lower than with clopidogrel for low (9.9%), intermediate (9.3%), and high (11.5%) expression.

Patients who had any gain-of-function CYP2C19 alleles exhibited an increased risk of bleeding with clopidogrel, but the increase was not significant. No effect on bleeding was seen for ticagrelor subjects with regard to CYP2C19, and no relationship was found between ABCB1 genotype and bleeding rates.

Ticagrelor was recently recommended for approval by a US Food and Drug Administration advisory committee.

Funding for this study was provided by AstraZeneca.

- MFP Wire Services
- 09-02-2010

By: Bruce Sylvester

STOCKHOLM, SWEDEN – Ivabradine significantly reduces cardiovascular mortality or heart failure hospitalisation in patients with heart failure, systolic dysfunction, and elevated heart rate, researchers said at the European Society of Cardiology Congress 2010.

“Compared with placebo, ivabradine reduced cardiovascular mortality or heart failure hospitalisation by a statistically significant 18%,” said Michel Komajda, MD, Department of Cardiology, University Pierre et Marie Curie and Pitie Salpetriere Hospital, Paris, France. “Overall, ivabradine treatment was safe and well tolerated.”

The Systolic Heart Failure Treatment With the IF Inhibitor Ivabradine Trial (SHIFT) sought to determine whether ivabradine produces a beneficial effect in patients with heart failure with an elevated heart rate.

Eligible patients had symptomatic heart failure and left ventricular ejection fraction <=35%, sinus rhythm with heart rate >=70 beats/minute, and a hospitalisation for heart failure within the past year and were on stable background therapy including a beta-blocker, if tolerated.

The investigators randomised 6,492 patients to ivabradine (n = 3,232) titrated maximally to 7.5 mg twice daily or to placebo (n = 3,260).

The primary endpoint of SHIFT was the composite of cardiovascular death or hospital admission for worsening heart failure. The average time of follow-up was 22.9 months.

Ivabradine significantly reduced the number of cardiovascular deaths or heart failure hospitalisations by 18% (P < .0001). Ivabradine treatment was also associated with a 26% drop in heart failure events that lead to hospitalisation or death.

"The SHIFT trial shows, for the first time, that lowering heart rate alone is of benefit to patients with heart failure," said Dr. Komajda. "This is a significant finding."

Funding for this study was provided by Servier Laboratories.

- MFP Wire Services
- 09-02-2010

By: Ed Susman

STOCKHOLM, SWEDEN – The use of a mitral annuloplasty system for patients with troublesome mitral valve regurgitation appears to be successfully performed through a percutaneous procedure, researchers said at the European Society of Cardiology Congress 2010.

“After 3 years, 64% of the patients are event free,” said Jan Harnek, M.D, Cardiac Catheterization La, Lund University Hospital, Lund, Sweden. “Implementation in the coronary sinus is feasible, easy and reproducible,” he said in his oral Hot-Line presentation.

He said that treatment with the MONARC device reduced mitral regurgitation and improved patients’ New York Heart Association class. The mean class at baseline was 2.7; after 3 years the mean class was 2.

However, he noted that the results are based on 13 patients out of 72 individual who were originally enrolled in the study. Of the original patients, 13 did not receive the implant; 16 of the patients died during the 3-year period; 14 other patients dropped out of the study; and 16 patients could not be evaluated due to missing data or protocol errors.

He said that researchers in the Clinical Evaluation of the Edwards Lifesciences Percutaneous Mitral Annuloplasty System for the treatment of Mitral Regurgitation (EVOLUTION) trial came to understand that use of device deigned to tighten area around the malfunctioning mitral valve may also cause compression to coronary arteries.

One patient died due to artery compression, he reported.

Dr. Harnek noted that the study was conducted to observe safety of the device, and a follow-up study with additional patients is being enrolled.

The average age of the patients was 70 years. About 72% of the patients were men. Patients were diagnosed with functional mitral valve regurgitation grade 2 to 4. The patients were required to have a left ventricle ejection fraction >25%.

The discussant for the study, Manuel Antunes, MD, Cardiothoracic Surgery, University Hospital, Coimbra, Portugal, suggested that the device is a long-way from prime time.

“The MONARC concept of annuloplasty is faulty and very dependent upon anatomincal variations,” he said. “The study is plagued by a small number of patients, many drop-offs, and unsatisfactory results. Surgery remains the only reasonable alternative, even in cases of severe ‘functional’/ischemic mitral regurgitation.”

Funding for this study was provided by Edwards Life Sciences.

- MFP Wire Services
- 09-01-2010