Calcium channel blockers and atrial fibrillation
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Calcium Channel Blockers and Atrial Fibrillation: A Comprehensive Overview
Introduction to Atrial Fibrillation and Calcium Channel Blockers
Atrial fibrillation (AF) is a common cardiac arrhythmia that can lead to significant morbidity and mortality. Calcium channel blockers (CCBs) are frequently used in the management of AF, particularly for rate control. This article synthesizes recent research on the efficacy and safety of CCBs in treating AF, comparing them with other therapeutic options such as beta-blockers and angiotensin II-receptor blockers (ARBs).
Efficacy of Calcium Channel Blockers in Rate Control
Comparison with Beta-Blockers
Several studies have compared the efficacy of CCBs and beta-blockers in controlling heart rate in AF patients. A systematic review found that intravenous diltiazem, a non-dihydropyridine CCB, was more effective than intravenous metoprolol in achieving rapid rate control in the emergency department setting10. Another study from the AFFIRM trial indicated that both CCBs and beta-blockers were effective in maintaining a resting heart rate below 110 beats per minute during AF episodes, but CCBs were associated with less bradycardia during sinus rhythm3.
Acute Rate Control and Hemodynamic Stability
In acute settings, the use of intravenous CCBs or beta-blockers for rapid ventricular response (RVR) in AF can lead to cardiogenic shock in patients with underlying systolic dysfunction due to their negative inotropic effects4. However, a retrospective study showed that adding a second AV nodal blocker (either CCB or beta-blocker) in patients who did not achieve rate control with the first agent resulted in heart rate control 46% of the time, with a low incidence of symptomatic bradycardia6.
Structural and Electrical Remodeling
Cilnidipine and AF-Related Remodeling
Cilnidipine, an N-/L-type CCB, has shown promise in suppressing autonomic, electrical, and structural remodeling associated with AF. In a study involving dogs, cilnidipine reduced autonomic changes, extracellular matrix gene expression, and atrial fibrosis, which are critical factors in AF pathophysiology2. This suggests that cilnidipine may offer additional benefits beyond rate control by addressing underlying remodeling processes.
Comparison with Angiotensin II-Receptor Blockers
J-RHYTHM II Study
The J-RHYTHM II study compared the effects of the ARB candesartan and the CCB amlodipine on the frequency of paroxysmal AF in hypertensive patients. The study found no significant difference in AF frequency reduction between the two groups, although blood pressure was better controlled in the CCB group1. This indicates that while CCBs are effective in managing blood pressure, they may not offer superior benefits over ARBs in reducing AF episodes.
Meta-Analysis Findings
A meta-analysis of randomized controlled trials found that ARBs were superior to CCBs in preventing AF recurrence and persistent AF in hypertensive patients. Specifically, the ARB telmisartan showed significant benefits over CCBs like amlodipine in reducing AF recurrence5. This suggests that ARBs may be more effective in long-term AF management compared to CCBs.
Safety and Efficacy in Heart Failure
Verapamil and Diltiazem in Heart Failure
The safety of CCBs in patients with AF complicated by congestive heart failure (CHF) remains a concern. Verapamil and diltiazem, both non-dihydropyridine CCBs, have been associated with hemodynamic and clinical deterioration in some patients with significant left ventricular dysfunction. However, diltiazem appears to have fewer negative inotropic effects compared to verapamil and does not exacerbate heart failure in most cases8.
Conclusion
Calcium channel blockers are effective in controlling heart rate in atrial fibrillation and offer additional benefits in reducing AF-related remodeling. However, their efficacy in preventing AF recurrence may be inferior to that of angiotensin II-receptor blockers. In patients with heart failure, the use of CCBs should be approached with caution due to potential negative inotropic effects. Overall, the choice of therapy should be individualized based on patient characteristics and comorbidities.
Sources and full results
Most relevant research papers on this topic
Randomized trial of angiotensin II-receptor blocker vs. dihydropiridine calcium channel blocker in the treatment of paroxysmal atrial fibrillation with hypertension (J-RHYTHM II study).
Candesartan does not have an advantage over amlodipine in reducing the frequency of paroxysmal AF in patients with paroxysmal AF and hypertension.
RCT
Large Human Trial
Highly CitedAn N-/L-Type Calcium Channel Blocker, Cilnidipine, Suppresses Autonomic, Electrical and Structural Remodeling Associated with Atrial Fibrillation.
Cilnidipine, a commercially available N-/L-type calcium channel blocker, effectively prevents atrial fibrillation by suppressing autonomic, electrical, and structural remodeling in dogs.
RCT
Animal Study
Rigorous JournalRate control in atrial fibrillation, calcium channel blockers versus beta-blockers
In patients with non-permanent atrial fibrillation, calcium channel blockers for rate control are associated with less bradycardia during sinus rhythm compared to beta-blockers.
RCTLarge Human TrialACUTE RATE CONTROL OF ATRIAL FIBRILLATION WITH RAPID VENTRICULAR RESPONSE USING INTRAVENOUS CALCIUM CHANNEL BLOCKERS OR INTRAVENOUS BETA BLOCKERS LEADS TO CARDIOGENIC SHOCK IN PATIENTS WITH UNDERLYING SYSTOLIC DYSFUNCTION
Intravenous calcium channel blockers or beta-blockers can cause cardiac shock in patients with underlying systemic dysfunction.
Very Rigorous JournalAngiotensin Receptor Blocker and Calcium Channel Blocker Preventing Atrial Fibrillation Recurrence in Patients with Hypertension and Atrial Fibrillation: A Meta-analysis
Angiotensin receptor blockers (ARB) are superior to calcium channel blockers in preventing atrial fibrillation recurrence and persistent AF in patients with hypertension and AF.
Meta-AnalysisRigorous JournalHeart rate outcomes with concomitant parenteral calcium channel blockers and beta blockers in rapid atrial fibrillation or flutter.
Adding a second nodal blocker to patients with rapid atrial fibrillation or flutter can achieve heart rate control 46% of the time without developing symptomatic bradycardia.
Observational StudyRigorous JournalComparison of four single-drug regimens on ventricular rate and arrhythmia-related symptoms in patients with permanent atrial fibrillation.
Diltiazem 360 mg/day is the most effective drug for reducing heart rate in patients with permanent atrial fibrillation, while calcium channel blockers diltiazem and verapamil also reduce arrhythmia-related symptoms.
RCTHighly CitedCalcium channel blockers for heart rate control in atrial fibrillation complicated by congestive heart failure.
Calcium channel blockers may help reduce ventricular response in patients with atrial fibrillation complicated by congestive heart failure, but their safety in chronic heart rate control remains to be proven.
Systematic ReviewTreatment strategies for new onset atrial fibrillation in patients treated on an intensive care unit: a systematic scoping review
Beta blockers or amiodarone may be superior to calcium channel blockers as first line therapy for new-onset atrial fibrillation in ICU patients, but limited evidence supports therapeutic anticoagulation during ICU admission.
Systematic ReviewRigorous Journal&bgr;-Blockers versus calcium channel blockers for acute rate control of atrial fibrillation with rapid ventricular response: a systematic review
Diltiazem may be more effective than metoprolol for rapid rate control in atrial fibrillation with rapid ventricular response, but high-quality randomized studies are needed.
Systematic Review