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How therapeutic fashion trumps medical evidence

Profit motives and fear of missing out or going against the trend, has led to health professionals following therapeutic fashions instead of questioning accepted procedures and following medical evidence instead, notes Medical Brief.

Writing in Medscape, Dr John M Mandrola writes: "I’ve been thinking a lot about how the standard of care in medicine is established and then becomes resistant to critical appraisal,  and these were not happy thoughts.

In fact, I’ve come to believe that too often, therapeutic fashion trumps medical evidence. Once it reaches a threshold, anyone who dares question it based on the evidence is considered a loon or a nihilist.

My point in what follows, beyond expressing frustration, is to induce people to consider how and why medical norms become established. And to consider the fashion of the day with a historical frame, recalling that we used to use hormone replacement therapy to prevent heart disease in postmenopausal women.

Coronary stents in patients with stable disease

A friend who is an interventional cardiologist told me about a middle-aged man with a severe narrowing in his right coronary artery. He had undergone a test for coronary artery calcium score that was abnormal. (I’ve written against doing these tests, but that is for another post.) This man exercised without limitations or symptoms. The abnormal calcium score led to a stress test, even though the guidelines say the test is to guide statin decisions. The result of the stress test was positive, and his doctor sent him for a cardiac catheterisation.

There is nothing unusual about this cascade. It is the therapeutic fashion.

My friend recommended against implanting a stent. He essentially said: “Sir, you have a narrowing, it is stable, and we will treat it medically with statins and other meds.” This is what the evidence shows, including the most recent ISCHEMIA trial.

But everyone went nuts. The family was upset, and the referring doctor was aghast. The patient went to another interventionalist and got his stent.

My friend went against the therapeutic fashion. Will he do it again? How many families and referring docs can a consultant afford to upset by following the evidence?

Left atrial appendage occlusion for the prevention of stroke

The theory that percutaneous left atrial appendage occlusion with a device would reduce stroke is plausible. Yet the evidence is extremely dubious. I’ve written about the evidence and posted my lecture arguing against this procedure.

Yet the US Food and Drug Administration (FDA) approved the device, and the therapeutic fashion has now normalised a preventive procedure with a major complication rate of at least 5%. Patients are being told you don’t have to take anticoagulants; you can have a device instead. And advertisements have intensified interest among patients.

I’ve debated this topic on five continents and have written about it in columns and journal articles. The therapeutic fashion has won.

I am now akin to my interventional friend: an outlier, a non-believer.

Lytic drugs

If you present to an emergency department with an acute stroke, there is a good chance you will receive a thrombolytic drug. There is also a decent chance that your emergency medicine doctor doesn't believe it works.

But neurologists believe it works, and hospitals have “stroke centres” based largely on using said drugs. The therapeutic fashion is that lytics should be used in acute stroke.

Yet the evidence is hardly clear. In 2018, I argued against the use of thrombolytic therapy for acute stroke. The emergency medicine literature is replete with critical appraisal of this practice. And a recent review – from a neurologist – suggested that baseline differences in the seminal National Institute of Neurological Disorders and Stroke (NINDs) trial occurred because of randomisation errors. The safety/efficacy balance is a major issue because lytic therapy increases the odds of devasting bleeding in the brain.

Yet anyone who expresses the view that we ought to repeat the NINDs trial is considered a fool.

Other notables: there are many more

Therapeutic fashion now awards sacubitril/valsartan the mantle of “best” renin-angiotensin inhibitor for heart failure. But its only clearly positive trial came against enalapril.

Electrophysiologists accept that atrial fibrillation (AF) ablation improves symptoms from AF, but it has never passed muster against a sham procedure.

In the intensive care unit, we cooled patients after cardiac arrest for years. It took not one but two trials to break the sclerosis of that thinking.

The dangers of therapeutic fashion

The Cardiac Arrhythmia Suppression Trial (CAST), published in 1991, found that the therapeutic fashion of suppressing premature ventricular contractions after myocardial infarction (MI) with antiarrhythmic drugs led to a more than doubling of death in the drug arm. This finding shocked the cardiology world because it shredded an ensconced practice.

I encourage you to read an account (link at the end of this article ) from British cardiologist John Hampton who tried to publish a small trial documenting higher mortality in post-MI patients treated with antiarrhythmic drugs 10 years before CAST. No journal would publish it – until after CAST had changed the fashion of the day.

Given that the number needed to kill in CAST was approximately 29, how many lives would have been saved without such attachment to a therapeutic fashion?

What causes therapeutic fashion

Fixing the problem means considering the causes. In many cases, especially the search for ischaemia, profit motive clearly plays a major role. But there is also the fear of missing out. If colleagues have accepted a procedure, and other hospitals are not only doing it but marketing it, then a doctor who does not do the procedure may feel inadequate, a lesser specialist. Never discount human nature in the cause of therapeutic fashion.

Doctors also have a strong inclination to want to do something. I sense that many neurologists and cardiologists simply want to help their patients. Not intervening with lytics or stents seems impotent.

Look inward…

I hope that clinicians in other fields consider their own therapeutic fashions. How secure is the evidence? How foolish will it look with the sharp eye of history?

While medical advances will render many of our practices archaic, which is expected, the question I propose is: would stronger and more neutral critical appraisal of our therapeutic fashions reveal now what future generations will surely come to know?

CAST Study details

Mortality and Morbidity in Patients Receiving Encainide, Flecainide, or Placebo — The Cardiac Arrhythmia Suppression Trial

Debra Echt, Philip Liebson, Brent Mitchell, Robert Peters, Dulce Obias-Manno, Allan Barker, Daniel Arensberg, Andrea Baker, Lawrence Friedman, Leon Greene, Melissa Huther, David Richardson, et al.

Published in The New England Journal of Medicine on 21 March 1991

Abstract

Background and methods
In the Cardiac Arrhythmia Suppression Trial, designed to test the hypothesis that suppression of ventricular ectopy after a myocardial infarction reduces the incidence of sudden death, patients in whom ventricular ectopy could be suppressed with encainide, flecainide, or moricizine were randomly assigned to receive either active drug or placebo. The use of encainide and flecainide was discontinued because of excess mortality. We examined the mortality and morbidity after randomisation to encainide or flecainide or their respective placebo.

Results
Of 1498 patients, 857 were assigned to receive encainide or its placebo (432 to active drug and 425 to placebo) and 641 were assigned to receive flecainide or its placebo (323 to active drug and 318 to placebo). After a mean follow-up of 10 months, 89 patients had died: 59 of arrhythmia (43 receiving drug vs. 16 receiving placebo; P = 0.0004), 22 of nonarrhythmic cardiac causes (17 receiving drug vs. 5 receiving placebo; P = 0.01), and 8 of noncardiac causes (3 receiving drug vs. 5 receiving placebo). Almost all cardiac deaths not due to arrhythmia were attributed to acute myocardial infarction with shock (11 patients receiving drug and 3 receiving placebo) or to chronic congestive heart failure (4 receiving drug and 2 receiving placebo). There were no differences between the patients receiving active drug and those receiving placebo in the incidence of nonlethal disqualifying ventricular tachycardia, proarrhythmia, syncope, need for a permanent pacemaker, congestive heart failure, recurrent myocardial infarction, angina, or need for coronary-artery bypass grafting or angioplasty.

Conclusions
There was an excess of deaths due to arrhythmia and deaths due to shock after acute recurrent myocardial infarction in patients treated with encainide or flecainide. Nonlethal events, however, were equally distributed between the active-drug and placebo groups. The mechanisms underlying the excess mortality during treatment with encainide or flecainide remain unknown.

NINDS Study details

Tissue Plasminogen Activator for Acute Ischaemic Stroke

The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group*

Published in The New England Journal of Medicine on 14 December 1995

Abstract

Background
Thrombolytic therapy for acute ischaemic stroke has been approached cautiously because there were high rates of intracerebral haemorrhage in early clinical trials. We performed a randomised, double-blind trial of intravenous recombinant tissue plasminogen activator (t-PA) for ischaemic stroke after recent pilot studies suggested that t-PA was beneficial when treatment was begun within three hours of the onset of stroke.

Methods
The trial had two parts. Part 1 (in which 291 patients were enrolled) tested whether t-PA had clinical activity, as indicated by an improvement of 4 points over base-line values in the score of the National Institutes of Health stroke scale (NIHSS) or the resolution of the neurologic deficit within 24 hours of the onset of stroke. Part 2 (in which 333 patients were enrolled) used a global test statistic to assess clinical outcome at three months, according to scores on the Barthel index, modified Rankin scale, Glasgow outcome scale, and NIHSS.

Results
In part 1, there was no significant difference between the group given t-PA and that given placebo in the percentages of patients with neurologic improvement at 24 hours, although a benefit was observed for the t-PA group at three months for all four outcome measures. In part 2, the long-term clinical benefit of t-PA predicted by the results of part 1 was confirmed (global odds ratio for a favourable outcome, 1.7; 95 percent confidence interval, 1.2 to 2.6). As compared with patients given placebo, patients treated with t-PA were at least 30 percent more likely to have minimal or no disability at three months on the assessment scales. Symptomatic intracerebral haemorrhage within 36 hours after the onset of stroke occurred in 6.4 percent of patients given t-PA but only 0.6 percent of patients given placebo (P<0.001). Mortality at three months was 17 percent in the t-PA group and 21 percent in the placebo group (P = 0.30).

Conclusions
Despite an increased incidence of symptomatic intracerebral haemorrhage, treatment with intravenous t-PA within three hours of the onset of ischaemic stroke improved clinical outcome at three months.

Dr John Mandrola is a cardiologist in St Matthews, Kentucky, USA.

 

Journal of the Royal Society of Medicine 2015 article –Therapeutic fashion and publication bias and the case of anti-arrhythmic drugs in heart attack by John Hampton (Open access)

 

NEJM article – Mortality and Morbidity in Patients Receiving Encainide, Flecainide, or Placebo — The Cardiac Arrhythmia Suppression Trial (Open access)

 

NEJM article – Tissue Plasminogen Activator for Acute Ischaemic Stroke (Open access)

 

Medscape article – Medical Necessity vs Therapeutic Fashion: How Evidence-Based Is Your Field of Medicine? (Open access)

 

See more from MedicalBrief archives:

 

Robust study finds stents no better than drugs for many, challenging current practice

 

FDA approves empagliflozin for HF regardless of ejection fraction

 

Study of 4m people shows statin intolerance is over-estimated and over-diagnosed

 

Clot busting medications reduce pulmonary embolism deaths

 

Hydroxychloroquine plus azithromycin doubles cardiovascular mortality risk

 

 

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