Heart rate slowing versus other pharmacological antianginal strategies

Relieving the symptoms of angina and improving the quality of life and functional status are important objectives in the management of patients with chronic stable angina. A high heart rate induces or exacerbates myocardial ischemia and angina because it both increases oxygen demand and decreases myocardial perfusion. Beta-Blockers are effective at reducing anginal symptoms largely by decreasing heart rate. Physician use and patient compliance may be limited by the side effects of Beta-blockers which include fatigue, depression and sexual dysfunction. Heart rate reduction can also be obtained by the calcium antagonists verapamil and diltiazem and by the new selective heart-rate-reducing agent ivabradine. Ivabradine (Procoralan) is a selective and specific I(f) inhibitor that acts on one of the most important ionic currents for the regulation of the pacemaker activity of sinoatrial node cells. Ivabradine has demonstrated dosedependent anti-ischemic and antianginal effects in a placebo-controlled study. The INITIATIVE trial is a large multicenter trial in which 939 patients with stable angina were randomized to ivabradine or atenolol. The noninferiority of ivabradine was shown in the INITIATIVE trial at all doses and for all criteria including time to limiting angina. The number of angina attacks per week was decreased by two thirds with both ivabradine and atenolol. In another trial of 1,195 patients, time to 1mm ST segment depression was increased by 45 s with ivabradine 7.5 mg b.i.d. and by 40 s with amlodipine 10 mg daily. Unlike beta-blockers, ivabradine is devoid of intrinsic negative inotropic effects and does not affect coronary vasomotion. A whole range of patients with angina may benefit from exclusive heart rate reduction with ivabradine, including those with contraindications or intolerance to the use of beta-blockers and patients that are insufficiently controlled by beta-blockers or calcium channel blockers.