Tag Archives: EP Mobile

What If My CHA2DS2-VASc Score Is One?

There is nothing simple about atrial fibrillation; it is a complicated, often overwhelming disease, both for patient and physician. One question that invariably comes up early on is the question of prophylactic anticoagulation for prevention of stroke. Who should receive anticoagulation? Which anticoagulant? How should anticoagulation be handled around the time of surgical procedures, or before and after ablation or cardioversion? How should anticoagulation be monitored? How should it be modified in patients with kidney or liver disease? Should anticoagulation be used in patients who have increased bleeding risks? Just the topic of anticoagulation in atrial fibrillation is overwhelming!  Too much for a short blog post. We’ll have to narrow this down further. Let’s talk about using risk scores to decide who should be placed on anticoagulation therapy.

chadsvascAtrial fibrillation risk scores were designed to assess stroke risk in patient populations with atrial fibrillation “without valvular heart disease.” I quoted that because “without valvular heart disease” is not well defined for this purpose. Certainly these risk scores don’t apply to patients with prosthetic heart valves, or with rheumatic mitral stenosis, but beyond that in practice these scores seem to be used even in patients with mild to moderate non-rheumatic valvular disease. The CHADS2 score is very simple, but has become passé in recent years. It is too gross a measure; people with low scores can still be at significant risk for stroke. It has been replaced by the CHA2DS2-VASc score in recently published guidelines. This score makes it much harder to achieve a score of 0 and escape anticoagulation. Using this risk score, both the 2012 European Society of Cardiology (ESC) and 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) atrial fibrillation guidelines recommend no anticoagulation if the score is zero, and full anticoagulation if it is 2 or greater. Where there is some hesitation, if not disagreement, is when the CHA2DS2-VASc score is 1.  Anticoagulate or not? The previous iteration of the guidelines leaned strongly toward anticoagulation for a CHA2DS2-VASc score of 1. The latest sets of guidelines are more equivocal. How to handle a score of 1 is particularly important when one realizes that female sex, on its own, is a risk factor in CHA2DS2-VASc with a point value of 1. Yes, half the people on the planet are born with a CHA2DS2-VASc score of 1 and by the old guidelines would require anticoagulation just on the basis of their sex.

A Swedish study published in 2012 sheds some light on this issue. The study concluded that, while female sex is a risk factor for stroke in atrial fibrillation if other risk factors are present, by itself, in women less than 65 years old without other risk factors, female sex does not confer a significant risk of stroke. The implication is that a CHA2DS2-VASc score of 1 that is only due to female sex does not warrant anticoagulation.

The results of this study were directly incorporated into the 2012 ESC guidelines (I note that Dr. Gregory Lip is a coauthor of both these guidelines and the Swedish study). Thus the recommendation by the ESC is full anticoagulation (aspirin and aspirin + clopidogrel are relegated to remote second-line therapy) for CHA2DS2-VASc score of 1 or higher, after excluding females with no other risk factors and age < 65 years, who (as with men with the same criteria) do not need anticoagulation.

The AHA/ACC/HRS 2014 atrial fibrillation guidelines are more vague than the ESC guidelines when the CHA2DS2-VASc score precisely equals 1. Cardiology guidelines are presented using a sort of quantified equivocation, with recommendations classified as I (should do it), IIa (reasonable to do it), IIb (you can consider doing it) or III (don’t do it). Not quite orthogonal, there are 3 levels of certainty as well: A (data derived from multiple randomized clinical trials), B (data from one randomized clinical trial), or C (“expert” opinion). Given this, it is interesting that anticoagulation for a CHA2DS2-VASc score of 2 or more is a class I, A level of evidence recommendation, and no anticoagulation for a score of 0 is a class IIa, B level of evidence recommendation. For a CHA2DS2-VASc score of 1 there is complete equivocation, with the following class IIb recommendation:

For patients with nonvalvular AF and a CHA2DS2-VASc score of 1, no antithrombotic therapy or treatment with an oral anticoagulant or aspirin may be considered. (Level of Evidence: C)

Addressing the possibility of a exclusion for females with a CHA2DS2-VASc score of 1, the guidelines state (again equivocating):

"In a study of Swedish patients with nonvalvular AF, women again had a moderately increased stroke risk compared with men; however, women younger than 65 years of age and without other AF risk factors had a low risk for stroke, and it was concluded that anticoagulant treatment was not required. However, the continued evolution of AF-related thromboembolic risk evaluation is needed."

This all creates a problem for physicians, patients (females especially), and also for the physician-programmer writing an app such as EP Mobile that calculates these risk scores and attempts to make recommendations. At present EP Mobile simply uses the old recommendations, as do most of the web-based online risk score calculators I surveyed (e.g. here and here). A user of EP Mobile pointed out to me that its recommendations are out of date.  Trying to fit such complexity into a small dialog box on a smartphone screen is challenging.  Nevertheless I will be updating the app so that its anticoagulation recommendations more precisely match current guidelines — at least until the next set of guidelines comes out.

EP Mobile Update Version 3.6 for Apple Devices

The reviewers at the Apple iTunes App Store have approved the revised version of the EP Mobile app.  For information on why the app needed to be revised, see my earlier posts on the subject.  I removed the drug dose calculators (note though that the Warfarin Clinic module was not removed), but added detailed drug dosing information and a creatinine clearance calculator that can be used while viewing the dosing information.  Other improvements to the app have been made as well.  The changelog is as follows:

Changes from version 3.5
* Removed drug dose calculators as requested by Apple (see developers guide section 22.9)
* Added new drug reference section with creatinine clearance toolbar
* Added creatinine clearance calculator
* Added right ventricular hypertrophy criteria
* Added D'Avila WPW accessory pathway location algorithm

I will release the new version in 2 days (March 22).  If for some reason you can’t live without the drug dose calculators, then don’t update the app.  Turn autoupdate off if it is on to prevent inadvertently updating the app.  Regardless of the lack of drug dose calculators, I encourage most people to update the app, because I think that using the new drug reference information in the app is a better way to determine drug dosages, and because I will continue to add new features to the app, which will not be available to those who do not update.

Note that Android users of EP Mobile still have access to the drug dose calculators, as well as the new features noted above.

I hope that at some point Apple changes its policy and adds physicians to the groups permitted to write apps that calculate drug doses.  After all, it’s what we do.

Countdown to version 3.6 release — Done! Released Mar 22, 2015!

[wpc_countdown theme=”flat-colors” now=”1426860240465″ end=”48″ bg=”#fff” padding=”5″]

 

Update on EP Mobile and Apple #2

As some of you are aware, the Apple App Store rejected an update to the EP Mobile app based on the presence of drug dose calculators in the app. The App Store guidelines state:

22.9 - Apps that calculate medicinal dosages must be submitted by the manufacturer of those medications or recognized institutions such as hospitals, insurance companies, and universities

For those who want more background on this issue, see these two previous posts (here and here).

I have decided to go ahead and remove the drug calculators from the app. All the drug calculator code remains in the app and, should Apple ever change their mind(s) on this policy, it will only require changing this single line of code to get them back.

// Sigh!
#define ALLOW_DRUG_CALCULATORS NO

I toyed with putting a backdoor into the app to activate the drug calculators, but I realize if I do something like that it would be my last Apple app. I have modified the app to make up for the loss of the drug calculators, and I think that with these changes you will continue to be satisfied by the app.

Here are the changes.

The creatinine clearance calculator had been embedded in the drug calculators, so it has been promoted to its own discrete module (which is something I should have done anyway a long time ago.

EP Mobile Main Menu Drug calculators gone, creatinine clearance calculator added
EP Mobile Main Menu
drug calculators gone, creatinine clearance calculator added

Instead of the drug calculators, there is a drug reference section. Each of the drugs that formerly had calculators now has detailed dosing information, as well as other useful information, akin to what you find in the Medscape app. (An aside: I think drug dosage information as opposed to drug dose calculators is acceptable to Apple, as it is present in Medscape and other medical apps. Medscape does not meet the Apple criteria mentioned above any more than EP Studios does: it is not “the manufacturer of those medications or [a] recognized institution […] such as hospitals, insurance companies, and universities.”).

Two new modules: Right Ventricular Hypertrophy and Drug Reference
Two new modules: Right Ventricular Hypertrophy and Drug Reference

What makes the drug reference section more useful than the similar information in Medscape is that there is a toolbar at the bottom of the screen that allows you to calculate a creatinine clearance on the fly, and then retains that information while you are trying to figure out the appropriate drug dose. Thus the only calculation done is the creatinine clearance; the physician and not the app decides of the dose. In many ways this is superior than having a drug dose calculator, because more information is presented that may be useful to help decide on the proper dose.  The drug reference section can also be expanded in the future to include information on other EP related drugs that don’t necessary require any calculations to dose, such as amiodarone or ibutilide.

A portion of the drug reference for dofetilide. Note the detailed dosing information and the Creatinine Clearance toolbar at the bottom showing the last calculated CrCl.

 

Finally the D’Avila WPW algorithm has been added, as well as a module on diagnosing right ventricular hypertrophy. I have left in the Warfarin Clinic module too. This module was not called out by Apple on the last review, so we shall leave it alone for now.

I will submit the update to Apple in the next 24 hours. Their review process usually takes about a week. If the approve it, I will not release the update right away, but will give some advance notice on Twitter. If you really can’t live without the drug calculators, then you should turn off auto-update and not update the app. I think though that the drug reference section with the built-in creatinine clearance calculator more than makes up for the loss of the drug calculators, and I encourage you to update the app when it is available.

If you happen to be best buds with Tim Cook, let him know that rule 22.9 is stupid and should be sacked.

Update on EP Mobile and Apple

This is an update on my previous post which dealt with Apple’s rejection of an update to the EP Mobile app because it contained drug dose calculators. According to a clause buried in the App Store Review Guidelines (section 22.9, to be precise),

22.9 apps that calculate medicinal dosages must be submitted by the manufacturer of those medications or recognized institutions such as hospitals, insurance companies, and universities.

EP Mobile has included such dosage calculators from its very first version, but for some reason the current update (which just added the D’Avila algorithm [PACE 1995;8:1615-1627] for determining accessory pathway location) triggered the discovery that the app was in violation of this rule. I was unaware of this rule, and I don’t think the rule was extant when I submitted the first iOS version of the app in 2012.

I submitted an appeal to Apple stating that as physicians have to calculate drug doses every day there does not seem to be any reason a physician-programmer should not be permitted to write an app to calculate drug doses. A drug company could only produce an app for their specific drug, so they could not duplicate the functionality of having multiple drugs from different companies in one app. I don’t see any incentive for a hospital, insurance company, or university to develop this kind of app, though I suppose it is possible they could. As a physician I developed the app because it was useful in my daily work. It makes figuring out drug doses for certain anti-arrhythmic drugs or anticoagulants much easier. As far as I know that specific functionality is not duplicated in the App Store.

Apixaban Dose Calculator
Apixaban Dose Calculator

Apple stuck to their guns and maintained the app update could not be approved. On Twitter a colleague tweeted this article from iMedicalApps of June 2013 which discusses the problems that Apple has with drug dosage apps. Apple is probably concerned about the FDA’s potential scrutiny of medical apps and possible legal liability for drug dose calculators that could give erroneous information. In any case this article points out that the Medscape app also provides drug dosing information (though only as written information, not as a calculator — I’m not certain, but it appears that the App Store Review Guidelines may have changed from banning dosing information altogether to just banning dose calculators). Medscape is owned by a private company (WebMD) and is neither drug company, hospital, insurance company nor university.

Medscape iPhone app provides drug dose information
Medscape iPhone app provides drug dose information

If the Medscape model for presenting drug dose information is legitimate in Apple’s eyes (as opposed to a violation that just hasn’t been noticed yet), it would be possible to retool my app to provide a creatinine clearance calculator followed by the specific dosing information for each drug. This is not as slick as having the answer just pop up in a dialog box, but on the other hand does show exactly what the dosing criteria are and removes the computer from the decision making process. However if I go that route there is no way to save one of my favorite parts of the app, the warfarin dose calculator. It is an implementation of an algorithm from this paper and provides suggested dosing changes for patients on chronic warfarin based on their INR, INR target, weekly total dose, and tablet size. It suggests how many pills the patient should take each day of the week. Whoever makes generic warfarin is not likely to develop a warfarin dose calculator like this, nor is anyone else.

iOS Simulator Screen Shot Feb 20, 2015, 7.50.40 PMiOS Simulator Screen Shot Feb 20, 2015, 7.50.23 PM

At this point I have requested further information from Apple. Apple has rejected the update to EP Mobile, but they have not requested I withdraw the current version of the program (which still has all the drug calculators in it). Certainly they might do so. In the hopes that their position will change, I have decided to withdraw the update and leave the app as is, unless Apple tells me otherwise. This is not a good long term strategy as I like to update the app frequently to keep it up to date with what is going on in electrophysiology, and I am now blocked from making any updates that don’t remove the drug calculator functionality. If I do release an update that does not contain the drug calculators, I will announce it well ahead of time on Twitter and on this site to give users the option not to update the app. I should also point out that the Android version of the app has not been challenged (Android is very hands off compared with Apple).

I am hoping that Apple will consider this further, based on this section of their App Store Review Guidelines:

This is a living document, and new Apps presenting new questions may result in new rules at any time. Perhaps your App will trigger this.

Who Can Write a Drug Dosage Calculator?

Several years ago I had an idea for a smartphone app that could be used to calculate doses for drugs that are prescribed frequently to patients with heart rhythm problems. These drugs include antiarrhythmics such as dofetilide and sotalol, and the new oral anticoagulants such as dabigatran and rivaroxaban. These drugs are handled by the kidneys, and dosage is dependent on kidney function. The package inserts for these drugs advise the correct drug doses based on the calculated creatinine clearance, a formula that involves the patient’s weight, age, sex and serum creatinine. Once the creatinine clearance is calculated, a lookup table is used to determine the dose. For example, here is the rivaroxaban dosing information:

xarelto

Medical calculator apps are common and invariably include a creatinine clearance calculator. The problem I had was trying to remember all the different creatinine clearance cutoffs for each dose of each drug. This seemed like perfect job for an app. Just fill in the information needed to calculate the creatinine clearance and have the app figure out the creatinine clearance and look up the dose. Thus my app EP Mobile was born. Over the years I have added many more modules to the app, including everything from algorithms localizing accessory pathways to entrainment mapping, but the original concept was to provide the drug dose calculators which remain a key part of the app.

Or maybe not. I routinely update the app, and submitted an update a week ago to Apple (not related to the drug dose calculators). For the first time ever I received a rejection from Apple. They quoted this from their App Store Submission Guidelines:

22.9 Apps that calculate medicinal dosages must be submitted by the manufacturer of those medications or recognized institutions such as hospitals, insurance companies, and universities

Attached were screenshots of the offending calculators:

A drug dose calculator
A drug dose calculator

I am a physician. Part of my job is to calculate medicinal dosages, as the legalese above terms it. This is not the job of hospitals, insurance companies, or universities. Ultimately I as a physician am legally responsible for calculating correct dosages. Yet somehow physicians are left off the list of those qualified to submit apps that calculate drug dosages. The development of an app that simply does what the drug package insert instructs the physician to do in order to calculate a drug dosage, but in an easier manner, should not be restricted to drug companies, hospitals, insurance companies (insurance companies?) or universities. The few of us physicians who are also app developers are certainly in as good a position as any of these other parties to develop apps like this. The algorithms to calculate these doses are extremely simple.  As my app is open-source, the source code is freely available for anyone to inspect to make sure the calculations are coded properly.

I appealed this decision to Apple and I hope they reconsider. I doubt they will. I see the handiwork of Apple’s legal department here. Don’t trust physicians to figure out what tools are useful on their own. Far better to let them go back to carrying around a bunch of drug company propaganda plastic rulers and let them do those creatinine clearance calculations by hand, using long division. Just like back in the good old days.