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Management of Stroke Patients: A One Man Show or A Tag-Team?

Atrial fibrillation (AF) increases risk of stroke up to 5 folds, resulting in considerable physical, cognitive impairment and high mortality1. Thus, AF related strokes are very expensive to treat compared to non-AF strokes2. Oral anticoagulation is a well-established therapy in the majority of stroke cases3. Warfarin reduces the risk of stroke by 64% and mortality by 30% compared to placebo3.

Recent data from the pinnacle registry presented by ‘Roopinder Sandhu, Edmonton, AB, Canada’ at the Scientific Sessions 2018, highlighted three key challenges in anti-coagulants management in stroke patients4. Data from a national outpatient registry reported over 700,000 patients had a diagnosis of atrial fibrillation5. Although oral anticoagulation use increased over time, around 40% of patients who are eligible for anti-coagulation never got started on therapy5. The second gap is sub-therapeutic dosing. Recent data from the orbit registry evaluated over 5700 patients who were recently started on a new drug and reported that one in eight patients were either underdosed or overdosed6. Further, there was a higher rate of adverse events in patients who had dosing that was sub therapeutic. The third gap is non-adherence. Data from administrative claims based on a large U.S. commercial insurance database, calculated adherence based on the fill date and the days of supply on the pharmacy claims over a median of 1.1 years7. Less than half of patients who were started on a drug therapy reached the threshold of proportion days covered of 80% or higher. This proportion was less for patients who were on Warfarin.

Given the public health consequences of untreated AF, it is necessary to evaluate different strategies to deliver stroke prevention therapy. Data from 30 randomized clinical trials evaluating the impact of pharmacists, versus standard care, showed superior results in the pharmacist care group in reducing systolic blood pressure (by 8 mm HG), diastolic blood pressure (by 4 mm HG) and total cholesterol (by 17 milligrams DL) and LDL (by 13 mg DL)10. This was done through educational intervention and identification of drug related problems followed by early feedback to the treating physician.

Roopinder added a few possible explanations to what could be driving such impact in the Canadian setting. Typically, a general practitioner would be dealing with patients with a higher evidence of chronic diseases. Further, patient demands often exceed the available physician capacity.

While these results collectively suggest that pharmacist led strategies may be a promising way forward because of their accessibility, drug expertise and their ability to build a trusted relationship. A few key things should be considered. First, that anticoagulation remains to be a complicated problem when it comes to individual patients, with many factors playing a role in the decision process including; medical history (as prior bleeding) and patient preferences. Second, while these interventions seem beneficial in the short-term it may lead to the same shortcomings in the long-term with the increase in demand on the pharmacists as the main provider.

Finally, a key question remains, would a collaborative approach between physicians and pharmacists yield better outcomes through reducing the burden on both providers and simultaneously increasing the time allocated to stroke patients on a case-by-case basis?

 

REFERENCES

  1. Developed with the special contribution of the European Heart Rhythm Association (EHRA), Endorsed by the European Association for Cardio-Thoracic Surgery (EACTS), Authors/Task Force Members, Camm, A. J., Kirchhof, P., Lip, G. Y., … & Al-Attar, N. (2010). Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). European heart journal31(19), 2369-2429.
  2. Stewart, S., Murphy, N., Walker, A., McGuire, A., & McMurray, J. J. V. (2004). Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the UK. Heart90(3), 286-292.
  3. Ruff, C. T., Giugliano, R. P., Braunwald, E., Hoffman, E. B., Deenadayalu, N., Ezekowitz, M. D., … & Yamashita, T. (2014). Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. The Lancet383(9921), 955-962.
  4. Sandhu, R. K., Guirguis, L. M., Bungard, T. J., Youngson, E., Dolovich, L., Brehaut, J. C., … & McAlister, F. A. (2018). Evaluating the potential for pharmacists to prescribe oral anticoagulants for atrial fibrillation. Canadian Pharmacists Journal/Revue des Pharmaciens du Canada151(1), 51-61.
  5. Marzec, L. N., Wang, J., Shah, N. D., Chan, P. S., Ting, H. H., Gosch, K. L., … & Maddox, T. M. (2017). Influence of direct oral anticoagulants on rates of oral anticoagulation for atrial fibrillation. Journal of the American College of Cardiology69(20), 2475-2484.
  6. Steinberg, B. A., Peterson, E. D., Kim, S., Thomas, L., Gersh, B. J., Fonarow, G. C., … & Piccini, J. P. (2015). Use and outcomes associated with bridging during anticoagulation interruptions in patients with atrial fibrillation: findings from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). Circulation131(5), 488-494.
  7. Yao, X., Abraham, N. S., Alexander, G. C., Crown, W., Montori, V. M., Sangaralingham, L. R., … & Noseworthy, P. A. (2016). Effect of adherence to oral anticoagulants on risk of stroke and major bleeding among patients with atrial fibrillation. Journal of the American Heart Association5(2), e003074.
  8. Santschi, V., Chiolero, A., Burnand, B., Colosimo, A. L., & Paradis, G. (2011). Impact of pharmacist care in the management of cardiovascular disease risk factors: a systematic review and meta-analysis of randomized trials. Archives of internal medicine171(16), 1441-1453.

 

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The Future of Wearable Technology & Detecting Atrial Fibrillation at AHA18

Like many of us, I have several family members who experience atrial fibrillation (AFib) regularly, as between 2-6 million people in the United States have this disorder. My father-in-law in particular has experienced difficultly with AFib recently and because he knows I study the heart, he often asks me about different treatment options and advice for handling his disease. Of course since I’m a basic research scientist, I always remind him that I’m not that kind of doctor and gently recommend he talk about it with his medical doctor and receive second opinions. However, when I got the chance to attend the AHA’s Scientific Sessions 2018 for the first time as an AHA Early Career Blogger, I knew I wanted to attend some sessions about AFib so I might have a little more to say for the next time I see my family. As a basic researcher, I don’t often get the often opportunity to hear from physicians about the day-to-day AFib issues they encounter with their patients.

Naturally, I jumped at the chance to attend the “Hey Doc, My Wristband Says I Have AF What Do I Do?” session yesterday afternoon. I was initially drawn to this particular event because my husband and I actually bought my father-in-law a wearable device last year for Christmas when he expressed interest in counting his steps and also keeping an eye on his heart rate, based on a comment from his doctor. Surprisingly though, the gift backfired since my father-in-law’s anxiety about his heart rate skyrocketed after he started wearing the device, because anytime it gave him an “abnormal” heart rate alert, he would get nervous and eventually ended up just staring at the device all day. So we all agreed it would be best if he just stopped wearing it. During this time, I kept wondering how accurate these devices actually are, and if my father-in-law actually was experiencing AFib that regularly, or maybe these were just false positives? Luckily, medical researchers primed to study this question were already on it, because the Apple Heart Study was initiated last November.

This collaboration between Apple and Stanford, spearheaded by Dr. Marco Perez, is a progressive clinical trial that uses data from Apple Watch devices from over 400,000 participants. The main purpose of this unprecedented study is to examine if AFib can be reliably diagnosed from irregular pulse notification data from wearable devices. In this session, Dr. Perez outlined how easy it is for participants for to sign up for the study and how a single reminder email from Apple actually doubled the amount of study participants almost over night, highlighting the power of these types of collaborations. One of the most interesting aspects of this study is how it is all done remotely. Interested participants just have to download the application, where they consent to study and then the algorithm monitors them. If an individual receives an irregular heart rate alert, they are recommended to a local doctor who can then prescribe them a patch monitor, which is mailed to the participants. After the monitor period, the participants simply mail the patch monitor back to Stanford where the scientists analyze the data. If AFib or other cardiac disorders are identified from this data, the participants are then referred to a doctor to get treatment. The clinical trial scientists never even meet the participants.

Dr. Perez mentioned that they are hopeful to have all of the data analyzed by the end of January as they are still collecting data everyday. Some of the most pressing questions this study hopes to answer is how accurate are these irregular heart rate alerts in diagnosing AFib? False positive rates are particularly of interest since many in the community think these devices could be causing alert when none is needed. Also an important thing to consider is how does the user’s behavior change after the alert? I know my father-in-law’s anxiety increased after getting these alerts, but I’m sure some people might find these devices as a comfort, particularly if this study reveals them to be accurate. Since many physicians here at the AHA 2018 Sessions have expressed that their patients are coming into their office with irregular alert data from their wearable devices, I’m sure doctors and users alike are excitedly awaiting the results of this powerful study – I know I am. The most important take home from this study truly has to be the actual size and manner in which it has been conducted. The results of this study have the potential to impact the future of clinical trials in general, since a trial of this magnitude run completely virtually has never been done before.

Picture source: https://www.apple.com/newsroom/2017/11/apple-heart-study-launches-to-identify-irregular-heart-rhythms/

 

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WATCHMAN: An Alternative to Warfarin for the High Risk Patient

“Wisdom consists of the anticipation of consequences”
Norman Cousins

I recently saw Mr. John Doe for atrial fibrillation (AF). Well into his eighties, he enjoys a good quality of life. This elderly gentleman is mostly unaware of his paroxysms of AF. However, he had also suffered a stroke in the past, and as such was managed with warfarin. He was lucky. Recently, he experienced a gastrointestinal hemorrhage, requiring temporary reversal of his anticoagulant in addition to receiving a few pints of blood. There were no apparent clinical triggers for this event. Mr. Doe is not a fictional person but is a typical example of what is a common clinical dilemma: how best to protect against stroke in a patient who is at high risk, yet becomes intolerant to warfarin.

Previously, these patients were commonly switched to aspirin alone as a poor alternative to anticoagulation. Most clinicians would feel apprehensive of taking a gamble switching to novel oral anticoagulants which do not have available reversal agents (at the time this blog was written).

So, what then?

Enter the “Watchman.”

The majority of thromboembolic strokes in patients with AF originate in the left atrial appendage (LAA). The function of this structure is to assist with atrial transport, however during AF, atrial blood flow becomes impaired and stasis can occur in the LAA leading to thrombus formation at this location. Fragmentation and embolization of thrombi can lead to stroke, which is commonly disabling. The presence of comorbid factors such as diabetes, heart failure among other clinical variables can further increase this risk [1].

The last several years has witnessed the development and refinement of procedures referred to as left atrial appendage occlusion. Although there are several of the devices available worldwide, I will refer to the WATCHMAN system which is approved for use in the United States. In brief, the WATCHMAN device resembles a small umbrella (Figure 1). The FDA approved the device for the purpose of preventing embolic stroke with non-valvular AF. The available data that lead to its approval implies a non-inferiority to warfarin [2,3]

the WATCHMAN device resembles a small umbrella

Figure 1. (accessed from www.bostonscientific.com; www.modernhealthcare.com)

The method of device introduction is via a femorally placed venous sheath delivered transseptally (from right to left atrium). The destination of the device is the ostium of the LAA (Figure 2). The ultimate goal of the procedure is to totally exclude the LAA from the chamber, thus preventing flow into and from the LAA, in effect precluding thrombus formation. The procedure is performed with the guidance of transesophageal echocardiography, and typically under general anesthesia. The duration of the implant typically does not exceed an hour. Patients are continued on warfarin during the initial perioperative phase.

the destination of the device is the ostium of the LAA

Figure 2. (Accessed from www.bostonscientific.com; openaccessjournals.com)

Generally, after a forty-five-day period, transesophageal echocardiography is repeated to confirm the absence of peri-device leaks and verify device endothelialization. If the results are favorable, patients can often stop warfarin and switch to antiplatelet therapy. Presently, the available evidence compares WATCHMAN to warfarin, and comparisons to other anticoagulants is lacking.

It appears that enthusiasm for the WATCHMAN appears to be growing. For patients who require long-term warfarin use, but are at risk for hemorrhagic complications, this device appears to be a very good option. Cumulative experience will invariably lead to further improvements in design and greater safety [4,5].
 
References

  1. Lip GY, Lane DA. Stroke prevention in atrial fibrillation: a systematic review. JAMA. 2015;313:1950-62
  2. Holmes DR Jr, Kar S, Price MJ, Whisenant B, Sievert H, Doshi SK, Huber K, Reddy VY Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial.J Am Coll Cardiol. 2014;64:1-12
  3. https://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=2 81&bc=ACAAAAAAAgAAAA%3d%3d&
  4. Reddy VY1, Doshi SK2, Kar S3, Gibson DN4, Price MJ4, Huber K5, Horton RP6, Buchbinder M7, Neuzil P8, Gordon NT9, Holmes DR Jr10; PREVAIL and PROTECT AF Investigators. 5-Year Outcomes After Left Atrial Appendage Closure: From the PREVAIL and PROTECT AF Trials.J Am Coll Cardiol. 2017;70:2964-2975
  5. Obeyesekere MN.Watchman Device: Left Atrial Appendage Closure For Stroke Prophylaxis In Atrial Fibrillation.J Atr Fibrillation. 2014; 7: 1099

Christian Perzanowski Headshot

Christian Perzanowski is an electrophysiologist in Tampa, FL. His main interests are in ablation techniques for atrial fibrillation and device therapy for congestive heart failure. He reports no conflicts of interests.

Apollo Beach, FL (05/17, CP)

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Deciphering the CABANA trial and what if anything do the results mean to the management of atrial fibrillation?

“The truth is rarely pure and never simple.”
Oscar Wilde

“Facts do not cease to exist because they are ignored.”
Aldous Huxley

As is apparent from my previous blogs, I am very passionate about atrial fibrillation (AF). Undoubtedly, the most common arrhythmia nationally, and likely worldwide, can cause disabling symptoms, lead to a stroke and exacerbate heart failure. In my experience, patients with AF can be categorized as either asymptomatic, or highly affected. Essentially the former are unaware of their diagnosis, and are often found to have AF by serendipity. Life is in fact very easy for them, as well as their clinicians: anticoagulate, rate control and move on.

Now, for those who are symptomatic, there exist management challenges. AF is classified as paroxysmal, which is an intermittent or periodic form of arrhythmia; persistent, which is a sustained form and generally felt to be a progressed state of AF; or permanent, where no interventions are done. There is a paucity of available antiarrhythmic agents to treat and suppress AF. Antiarrhythmic drugs have earned a reputation of not being very effective while causing significant systemic adverse effects. Clinicians who care for symptomatic AF patients have certainly observed them to often experience shortness of breath, chest discomfort, loss of stamina, sensation of tachycardia and in some cases heart failure. Not uncommonly, these symptoms lead to anxiety as well as a compromised quality of life. In short, these patients must be treated.

Over the last decade, the techniques employed to treat AF by catheter-based means have improved in efficacy, even for more advanced forms of persistent AF. Although far from ideal, a number of studies have demonstrated ablation methods (e.g. radiofrequency, referred to colloquially as “heat” or cryoablation, “freezing”) to be superior to attempts at drug suppression. This is no surprise, as ablation addresses the problem directly (e.g. preventing AF from initiating) by calculated tissue destruction. While repeat studies are sometimes needed, the improvement in quality of life and improvement in heart failure class (such as observed with CASTLE-AF, AATAC) are known benefits1,2.

CABANA (Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation Trial) sought to determine whether AF ablation versus antiarrhythmic drug therapy could prevent a composite endpoint of total mortality, disabling stroke, serious bleeding, or cardiac arrest1. This was a large randomized study with over 2,000 patients. The results, which were presented at the annual Heart Rhythm Society last month, yielded a rather disappointing result: ablation was not superior to drugs for preventing the above composite endpoint2. That’s a rather dubious final score.

In spite of acknowledging what Wilde and Huxley might say, I would like to reconcile several of CABANA’s limitations:

– Personally, I have a grievance with the use of a “composite score” in the above scenario; stroke and “serious bleeding” are in no way equivalent; mechanistically, how would the investigators theorize that ablation could prevent a cardiac arrest?
– Death, while inevitable is indeed a categorical variable, one is either alive or not. Given that the causes of death are innumerable, it does not seem appropriate to consider that ablation could prevent all causes of death. Rather than try to postulate that ablation, or a potpourri of antiarrhythmics could stave of death, a more appropriate measure would be to ascertain prevention of death from heart failure.
– Approximately 25% of patients assigned to drug therapy crossed to ablation. Notably, some sources cited difficulty in enrollment as patients and referring physicians likely felt that ablation would be more beneficial.
– The ablation techniques used, as were the drugs prescribed, were left to the discretion of the treating physicians. Hence, the methods employed were not uniform, and paroxysmal AF cases were pooled with more advanced forms of persistent AF.
– How about continued drug therapy after ablation? The POWDER-AF investigators were able to show less AF burden with continued antiarrhythmic support following AF ablation. This should be expanded upon with larger studies.

From my perspective, I do not believe that CABANA results will affect my practice. Many of us will be curious to see publications regarding future subanalysis. In my opinion, patients who are very symptomatic with AF and have not responded to antiarrhythmics should be treated with AF ablation, and especially those who have developed cardiomyopathy or worsened heart failure as a result of AF6.

References

  1. http://circ.ahajournals.org/content/early/2016/03/30/CIRCULATIONAHA.115.019406
  2. https://www.nejm.org/doi/full/10.1056/NEJMoa1707855
  3. https://clinicaltrials.gov/ct2/show/NCT00911508
  4. https://www.nhlbi.nih.gov/news/2018/atrial-fibrillation-catheter-ablation-or-drug-therapy-results-are
  5. Duytschaever M, Demolder A, Phlips T, Sarkozy A, El Haddad M, Taghji P, Knecht S, Tavernier R, Vandekerckhove Y, De Potter T. Pulmonary vein isolation With vs. without continued antiarrhythmic Drug treatment in subjects with Recurrent Atrial Fibrillation (POWDER AF): results from a multicentre randomized trial. Eur Heart J. 2018;39:1429-1437
  6. https://www.hrsonline.org/Policy-Payment/Clinical-Guidelines-Documents/2017-HRS-EHRA-E CAS-APHRS-SOLAECE-Expert-Consensus-Statement-on-Catheter-and-Surgical-Ablation-of-Atrial-Fibrillation

Christian Perzanowski Headshot
Christian Perzanowski is an electrophysiologist in Tampa, FL. His main interests are in ablation techniques for atrial fibrillation and device therapy for congestive heart failure. He reports no conflicts of interests.

sunset in tampa, florida

Tampa, FL (8/17 CP)