CALCIUM-CHANNEL BLOCKERS IN HEART-FAILURE

[摘要] The rationale for the use of calcium channel blockers in patients with chronic heart failure hes in their vasodilator action, antiischemic effect, ability to lessen left ventricular diastolic dysfunction and data showing their effect in preventing progression of myocardial dysfunction in animals with cardiomyopathy. Despite initial studies reporting improvement of the hemodynamic profile with nifedipine, further evaluation showed variable results, with hemodynamic worsening seen in up to 29% of patients. Longer term controlled studies evaluating symptoms and clinical status demonstrated worsening chronic heart failure in similar to 25% of patients within 8 weeks of nifedipine therapy. Although diltiazem has a lesser myo cardial depressant effect and its short-term use was associated with less frequent hemodynamic and clinical worsening, long term exposure to the drug in a large group of patients with chronic heart failure due to left ventricular systolic dysfunction after myocardial infarction resulted in an increased incidence of cardiac events, with worsening heart failure and death. The use of verapamil in a similar patient cohort showed the loss of its demonstrated protective effect in patients with clinical evidence of heart failure. In an attempt to improve the safety of calcium channel blockers, the following approaches were suggested: 1) use of second-generation drugs with less myocardial depressant effect; 2) concomitant use of angiotensin-converting enzyme inhibitors to prevent reported neurohormonal activation; and 3) development of drugs with favorable neurohormonal effects. These approaches led to mixed results. The use of some second-generation calcium channel blockers such as nisoldipine, felodipine and nicardipine resulted in no change or worsening of clinical status, which did not seem to be prevented by concomitant use of angiotensin-converting enzyme inhibitors. A recent study using amlodipine demonstrated improvement of both the clinical and neurohormonal profiles. Two large ongoing studies are evaluating the effects of felodipine and amlodipine on morbidity and mortality of patients with chronic heart failure and are likely to provide further information regarding the role of calcium blockers in the treatment of this condition.

[发布日期] 1993-10-01

[效力级别]  Proceedings Paper