Atrial Fibrillation 101
A classic clinical axiom for atrial fibrillation (AF) is “irregularly irregular rhythm.” The irregular rhythm, or arrhythmia, results from abnormal electrical impulses in the heart. The irregularity can be continuous or intermittent.
Normal heart contractions begin as an electrical impulse in the right atrium. This impulse comes from an area of the atrium called the sinoatrial or sinus node, the “natural pacemaker.” As the impulse travels through the atrium, it produces a wave of muscle contractions, causing the atria to contract. The impulse reaches the atrioventricular (AV) node in the muscle wall between the 2 ventricles. There, it pauses, giving blood from the atria time to enter the ventricles. The impulse then continues into the ventricles, causing ventricular contraction that forces the blood out of the heart, completing a single heartbeat. In a person with a normal heart rate and rhythm, the heart beats 50 to 100 times per minute. A heart rate less than 50 beats per minute is considered slow (bradycardia), and a heart rate more than 100 beats per minute is considered fast (tachycardia).
In AF, multiple impulses travel through the atria at the same time. Instead of a coordinated contraction, the atrial contractions are irregular, disorganized, chaotic, and very rapid. The atria may contract at a rate of 400 to 600 per minute. These irregular impulses reach the AV node in rapid succession, but not all of them make it past the AV node. Therefore, the ventricles beat slower, often at rates of 110 to 180 beats per minute in an irregular rhythm. The resulting rapid, irregular heartbeat causes an irregular pulse and sometimes a sensation of fluttering in the chest.
Stroke is a devastating complication of AF. In AF, the chaotic heart rhythm may cause blood to pool in the heart’s upper chambers (atria) and form blood clots. If a clot forms, a piece of the clot could dislodge from the heart and travel to the brain. There it might block blood flow, causing a stroke resulting in temporary or permanent brain dysfunction/damage. Pharmacotherapy for AF traditionally has 3 goals: slow down the heart rate, restore and maintain normal heart rhythm, and prevent stroke.
Is Dabigatran Use in AF Cost-Effective?
According to an analysis of data from the RE-LY trial by Shah and Gage published June 7, 2011, in Circulation, benefits of dabigatran 150 mg twice daily vs warfarin therapy outweigh costs in AF patients with a moderate to high risk of stroke and/or hemorrhage, unless they maintained excellent international normalized ratio (INR) control with warfarin therapy. Warfarin was cost-effective in patients with only moderate risk for those complications, unless INR control was considered poor. Researchers based their analysis on a hypothetical cohort of 70-year-old patients with AF who were consistent with the RE-LY population, placing the annual cost of dabigatran therapy at $3240 and of warfarin at $545.
Dabigatran 150 mg twice daily was associated with a qualityadjusted survival of 8.65 quality-adjusted life-years (QALYs), compared with 8.54 QALYs for dabigatran 110 mg twice daily and 8.4 QALYs for warfarin. Overall, the higher dabigatran dose cost $86,000 per QALY, compared with $150,000 per QALY for warfarin.
But dabigatran 150 mg twice daily met the cost-effectiveness threshold among patients with moderate stroke risk, reflected by a CHADS 2 score of 2, as long as the risk of hemorrhage was put at 6% per year. It was cost-effective at any risk of hemorrhage among patients with a greater stroke risk—that is, a CHADS 2 score of ≥3. It was never cost effective when the CHADS 2 score was only 0 or 1.
Simvastatin Use Associated With Increased Risk of Myopathy and Rhabdomyolysis
Based on data from the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) trial and given an increased risk of muscle damage, a June 2011 FDA communication states that physicians should limit prescribing the high-dose simvastatin 80 mg unless the patient has already been taking the drug for 12 months and there is no evidence of myopathy. “Simvastatin 80 mg should not be started in new patients, including patients already taking lower doses of the drug,” the FDA wrote.
Also due to increased risk, the simvastatin dose should not exceed 10 mg in patients taking amiodarone, verapamil, or diltiazem concurrently, or 20 mg in patients taking amlodipine or ranolazine. The FDA notes that the risks of myopathy and rhabdomyolysis were highest in the first year of treatment and that older age and female gender increased the risks. These recommendations/warnings will soon be incorporated into the drug’s label. PT
Mr. Brown is professor emeritus of clinical pharmacy and a clinical pharmacist at Purdue University College of Pharmacy, Nursing, and Health Sciences, Department of Pharmacy Practice, West Lafayette, Indiana.
In Seniors: Consider CMV Serostatus
When Recommending Flu Vaccine
Older people who have cytomegalovirus seem to have less robust responses to the trivalent influenza vaccine than those who do not have CMV.
News from the year's biggest meetings
Clinical features with downloadable PDFs