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Calcium channel blockers in heart failure
1Department of Medicine, University of Southern California School of Medicine, Los Angeles 90033.
Insights
Calcium channel blockers show limited benefit and potential harm in chronic heart failure patients. Studies indicate risks of worsening heart failure and cardiac events, necessitating careful consideration of their use.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Calcium channel blockers (CCBs) are considered for chronic heart failure (CHF) due to vasodilatory and anti-ischemic properties.
- Potential benefits include improved diastolic function and prevention of myocardial dysfunction in animal models.
Purpose of the Study:
- To evaluate the efficacy and safety of CCBs in patients with chronic heart failure.
- To review the outcomes of CCB therapy in various patient cohorts with heart failure.
Main Methods:
- Review of clinical studies and controlled trials involving CCBs (nifedipine, diltiazem, verapamil) in CHF patients.
- Analysis of hemodynamic profiles, clinical status, and cardiac events.
Main Results:
- Nifedipine showed initial hemodynamic improvements but led to worsening heart failure in up to 29% of patients.
- Diltiazem had less myocardial depression but long-term use in post-MI patients increased cardiac events and mortality.
- Verapamil lost its protective effect in patients with clinical heart failure.
Conclusions:
- CCBs have variable and often negative effects on chronic heart failure outcomes.
- Strategies to improve CCB safety, such as using newer agents or combination therapy, yielded mixed results.
- Careful patient selection and risk-benefit assessment are crucial when considering CCBs for heart failure.
Abstract:
The rationale for the use of calcium channel blockers in patients with chronic heart failure lies 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 approximately 25% of patients within 8 weeks of nifedipine therapy. Although diltiazem has a lesser myocardial 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.(ABSTRACT TRUNCATED AT 250 WORDS)