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A subgroup analysis of the ASSOCIATE study: Ivabradine improves exercise capacity in patients with stable angina pectoris receiving maximal tolerated dose of beta-blockers

Authors: J. Tardif1, P. Ponikowski2, T. Kahan3, On Behalf Of The Study Investigators1, 1Montreal Heart Institute - Montreal - Canada, 2Clinical Military Hospital, Medical Wroclaw University (2nd Cardiology Department) - Wroclaw - Poland, 3Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital - Stockholm – Sweden

Purpose: Ivabradine, a selective If current inhibitor, is a novel agent for angina treatment due to its heart rate (HR)-reducing properties. Since the beneficial effect of ivabradine in patients already receiving a β-blocker could depend on the β-blocking level reached in these patients, the team analyzed anti-ischemic efficacy of ivabradine in patients already receiving a dose of β-blocker judged as maximal.

Method: ASSOCIATE was a double-blind study in 889 patients (84% male) with documented CAD and a history of stable angina already treated with atenolol 50 mg od and randomized to receive ivabradine (5 mg bid, uptitrated to 7.5 mg bid) or placebo (n=441 and 434, respectively). Patients underwent treadmill ETT (Bruce protocol) at baseline and after 4 months at trough of drug activity. Current analysis was performed in a subgroup of patients in whom atenolol 50 mg od could be judged as maximal in terms of objective HR, haemodynamic, ECG criteria (resting HR≤ 60 bpm and/or supine systolic BP≤ 100 mmHg and/or mean PR interval ≥ 200 ms at baseline; n=80 in ivabradine group, n=64 in placebo group).

Results: Improvement in all ETT parameters observed with addition of ivabradine in patients in whom dose of atenolol could be judged to be maximal was comparable to the improvement observed in whole population of the study (Full analysis set, ivabradine n=441, placebo n=434) (Table).

 

 

Ivabradine

Placebo

P value

Total exercise duration, s

Full analysis set

24±65

8±64

<0.001

 

Maximal β-blocker dose

27±63

9±71

0.066

Time to 1-mm ST depression, s

Full analysis set

46±93

15±87

<0.001

 

Maximal β-blocker dose

47±85

15±87

0.018

Time to angina onset, s

Full analysis set

49±83

23±79

<0.001

 

Maximal β-blocker dose

51±94

18±83

0.013

Time to limiting angina, s

Full analysis set

26±66

9±64

<0.001

 

Maximal β-blocker dose

28±63

9±71

0.05

Conclusion: In patients with stable angina receiving doses of β-blockers that could be judged to be maximal, the addition of ivabradine improves exercise capacity equivalent to that observed in patients receiving lower doses of β-blockers. Ivabradine may be valuable addition for patients with remaining ischemia despite high doses of β-blockers.

 


Source:ESC 2010
Compiled and edited by the Editorial team and approved by Expert panel of CardioValens.com

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