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. Β-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 Β-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
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 Β-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 Β-blockers and patients that are
insufficiently controlled by Β-blockers or calcium channel blockers.
Copyright / Drug Dosage
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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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