Amlodipine and heart failure
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Amlodipine and Heart Failure: A Comprehensive Review
Introduction to Amlodipine in Heart Failure
Amlodipine, a calcium channel blocker, is widely used for treating hypertension and angina pectoris. However, its role in heart failure, particularly in patients with severe chronic heart failure, has been a subject of extensive research. This article synthesizes findings from multiple studies to provide a clear understanding of amlodipine's effects on heart failure outcomes.
Amlodipine and Mortality in Severe Chronic Heart Failure
General Findings
Several studies have investigated the impact of amlodipine on morbidity and mortality in patients with severe chronic heart failure. The PRAISE study, which included 1,153 patients with severe heart failure, found that amlodipine did not significantly increase cardiovascular morbidity or mortality compared to placebo1. However, a subgroup analysis revealed that amlodipine might reduce the risk of death in patients with nonischemic cardiomyopathy1.
Nonischemic Cardiomyopathy
Further research, including the PRAISE-2 study, focused on patients with nonischemic cardiomyopathy. This study concluded that amlodipine did not significantly reduce the risk of death or hospitalization for heart failure in these patients2. When combining data from both PRAISE trials, there was no significant effect of amlodipine on mortality, indicating that its benefits might be limited or non-existent in this subgroup2.
Mechanisms of Action: Cytokine Modulation
Cytokine Levels
The potential mechanisms by which amlodipine might benefit heart failure patients include modulation of cytokine levels. The PRAISE trial measured levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in patients with congestive heart failure. While TNF-alpha levels remained unchanged, IL-6 levels were significantly reduced in patients treated with amlodipine, suggesting a possible anti-inflammatory effect3.
Amlodipine and Cause-Specific Mortality
Sudden Death and Pump Failure
In advanced heart failure, cause-specific mortality patterns were analyzed. Amlodipine treatment resulted in a greater relative reduction in sudden deaths compared to pump failure deaths, particularly in patients with nonischemic heart failure4. This suggests that amlodipine may have a protective effect against sudden cardiac events in this subgroup.
Exercise Capacity and Quality of Life
Exercise Tolerance
Studies examining the effects of amlodipine on exercise capacity and quality of life in heart failure patients have shown mixed results. In two large multicenter trials, amlodipine did not significantly improve exercise tolerance or quality of life compared to placebo6. These findings suggest that while amlodipine may have some hemodynamic benefits, it does not translate into improved functional capacity for patients.
Clinical Outcomes in Dilated Cardiomyopathy
Korean Nationwide Cohort Study
A large retrospective cohort study in Korea investigated the long-term effects of amlodipine in patients with dilated cardiomyopathy. The study found that amlodipine use was associated with a significantly lower risk of all-cause death and heart failure rehospitalization over a five-year period8. This suggests that amlodipine may offer some survival benefits in this specific patient population.
Conclusion
The role of amlodipine in heart failure management remains complex and somewhat controversial. While it does not appear to increase morbidity or mortality in severe chronic heart failure, its benefits are more pronounced in patients with nonischemic cardiomyopathy. The reduction in IL-6 levels and potential protective effects against sudden death highlight possible mechanisms of action. However, the lack of significant improvement in exercise capacity and quality of life suggests that amlodipine's benefits may be limited to specific subgroups. Further research is needed to fully understand its role and optimize its use in heart failure treatment.
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Most relevant research papers on this topic
Effect of amlodipine on morbidity and mortality in severe chronic heart failure. Prospective Randomized Amlodipine Survival Evaluation Study Group.
Amlodipine does not increase cardiovascular morbidity or mortality in patients with severe heart failure, but may reduce the risk of death in nonischemic cardiomyopathy patients.
RCT
Large Human Trial
Highly CitedEffect of amlodipine on the survival of patients with severe chronic heart failure due to a nonischemic cardiomyopathy: results of the PRAISE-2 study (prospective randomized amlodipine survival evaluation 2).
Amlodipine does not show a favorable effect on survival in patients with heart failure due to a nonischemic cardiomyopathy, regardless of underlying coronary artery disease.
RCTLarge Human TrialHighly CitedRole of cytokines in the mechanism of action of amlodipine: the PRAISE Heart Failure Trial. Prospective Randomized Amlodipine Survival Evaluation.
Amlodipine lowers IL-6 levels in patients with congestive heart failure, potentially contributing to its beneficial effects in heart failure by reducing cytokine overexpression.
RCTHighly CitedEffect of amlodipine on mode of death among patients with advanced heart failure in the PRAISE trial. Prospective Randomized Amlodipine Survival Evaluation.
Amlodipine reduces sudden and pump failure deaths in nonischemic heart failure patients, but has no effect on cause-specific mortality in ischemic cardiomyopathy.
RCTLarge Human TrialHighly CitedEffects of amlodipine in patients with chronic heart failure.
Amlodipine has a limited role in patients with ischemic heart failure, but may be beneficial for those with nonischemic disease.
RCTEffects of amlodipine on exercise tolerance, quality of life, and left ventricular function in patients with heart failure from left ventricular systolic dysfunction.
Amlodipine 10 mg/day addition to standard therapy in heart failure patients does not significantly improve exercise time or quality of life, and does not increase the incidence of adverse events.
RCTLarge Human TrialCircadian rhythm and sudden death in heart failure: results from Prospective Randomized Amlodipine Survival Trial.
Sudden death in advanced heart failure patients shows a PM peak, not an AM peak, suggesting circadian sympathetic activation does not strongly influence these events.
RCTImpact of amlodipine on clinical outcomes for heart failure in patients with dilated cardiomyopathy: a Korean nationwide cohort study
Amlodipine use after hospitalization for heart failure in patients with dilated cardiomyopathy is associated with a lower risk of all-cause death and heart failure rehospitalization over a 5-year period.
Observational StudyBeneficial effects of amlodipine in a murine model of congestive heart failure induced by viral myocarditis. A possible mechanism through inhibition of nitric oxide production.
Amlodipine has a protective effect against myocardial injury in a murine model of congestive heart failure induced by viral myocarditis, potentially due to inhibition of nitric oxide production.
Highly CitedAmlodipine. A reappraisal of its pharmacological properties and therapeutic use in cardiovascular disease.
Amlodipine effectively lowers mild to moderately elevated blood pressure and relieves angina symptoms, offering potential for patients with angina pectoris and congestive heart failure.
Highly Cited