Drug Alerts: Keeping It All In Perspective

The Food and Drug Administration (FDA) is alerting us to potential dangers of the drug dronederone (Multaq), a relatively new medication indicated for the treatment of atrial fibrillation (AF).  There are preliminary data from a study suggesting a two-fold increase in the risk of death, stroke and hospitalization among patients randomized to this therapy.  This is, of course, concerning news to the more than 200,000 recipients of Multaq prescriptions and to us doctors who had hoped for a less toxic therapy for AF.

The jury is obviously still out on the use of Multaq and the current news needs to be taken in context.  The FDA warning is based on a single research study and the information needs to be digested and dissected by experts in the community.  At this point I am not making any changes to my prescribing patterns based on this one piece of information and I look forward to more conclusive findings and guidelines.

AF is the single most common rhythm abnormality that we encounter and its severity runs the gamut from nuisance to life-threatening menace.  Therapy for this disease has been around for many years but has been only variably successful.  Multaq is the newest in a long line of medications meant to force the heart back into normal rhythm and has been a hopeful new choice among drugs that have a long and checkered history of safety and tolerability.  In order to put in perspective the latest FDA warning I think it’s illustrative to recall our previous choices for treatment of AF.

Digoxin.  I like this medication and still use it in my patients with good success, but a brief review of its history is in order.  The cardiac properties of digitalis (an extract of the lovely foxglove flower) have been known for centuries.  Almost immediately the earliest practitioners of cardiac pharmacology learned of digitalis’s toxicity and relied on the outward manifestation of digitalis poisoning to aid them in dosing (as I reported in a previous blog post—one of my all-time favorites):

Dr. Withering would blend the leaves and petals of the plant and distill them into a soupy mix that he would feed to his patients.  Over time (and with several notable failures) the good doctor learned to give just enough to bring on nausea, weakness and a peculiar change in vision (the colorful world starts to fade to shades of yellow).  The goal of therapy was to saturate the patient to within a sip or two of fatal overdose.

For all of you on digoxin you need not fear—our dosing regimens are far less aggressive and we now have reliable lab assays that can alert us to any degree of early toxicity.  Still, I have to believe that a drug like digoxin, if it were a new therapy being brought to market by a pharmaceutical company, would probably not get FDA approval in this day of strict oversight—it’s simply not a “clean” enough medication.  Thankfully for us cardiologists and the patients currently getting benefit from digoxin, this drug will remain in use indefinitely.

Aspirin.  How on earth could something as benign as aspirin be a problem medication? you may ask.  Another age-old compound, acetylsalicylic acid is a cheap and effective drug that can be taken in low-dose on a daily basis to decrease the risk of stroke and heart attack and can serve as a mild blood thinner for low-risk patients with chronic AF.  Take too much, though, and your ears will ring like you attended an AC/DC concert, your blood will become acidic, and you’ll develop painful and dangerous erosions in the lining of your stomach that could land you in the hospital with a gastrointestinal bleed.  Aspirin is another drug that would probably not pass FDA muster if it were being brought to market these days—it would invariably be compared to safer and less toxic platelet blockers like Plavix and Effient and would come away looking more like poison than therapy.

Quinidine.  We don’t use this one anymore, but it was a viable option up until about 20 years ago.  I include it in this list to simply show you how much the medical community used to put up with in an attempt to treat AF.  Quinidine, derived from the bark of the cinchona tree (I’m looking to plant one of these in my foxglove and belladonna garden), had been used for decades as a treatment for malaria before Danish sailors discovered that their pulse evened out every time they took the drug.  Like Multaq, quinidine promotes stabilization of normal heart rhythm, but at a considerably higher cost.  Not only does it interact with numerous medications, quinidine can also trigger bleeding problems (thrombocytopenia), liver inflammation, weakness (myesthenia gravis), ringing in the ears, and life-threatening arrhythmias.  This last little quirk used to be common enough that it even had a name: quinidine syncope.  These sudden fits of fainting were nothing more than episodes of near cardiac arrest and were something patients just lived with (until they no longer did).

Warfarin (Coumadin).  This drug was developed as rat poison—need I say more?  (I actually do say more, and if you’re really bored click here).

Amiodarone.  Reading the side effect section in the package insert for amiodarone will give you more goose bumps than watching a midnight showing of a Wes Craven flick.  Its long-term toxicities can include damage to the liver, thyroid gland, lungs and eyes, and it tends to interact with a long list of other drugs.  Nevertheless, amiodarone is a very effective medication that we use frequently but monitor closely.  In patients with congestive heart failure, amiodarone is actually the safest and best-proven drug we have in our arsenal of rhythm-controlling prescriptions.

The use of medications, including the most modern and well-studied, is a balance of risks and benefits.  All drugs are inherently designed to poison something—a metabolic pathway, a cell-surface receptor protein, a functional enzyme—in order to provide the benefit we seek and are thus bound to have side effects and toxicities in certain individuals.  All the drugs listed above are chemicals that we employ successfully (or have used in the past) despite their weaknesses as long as we judiciously choose the proper recipients and watch them closely.  Multaq is no exception and it’s best to bear this in mind as we wait for more information.