Eminence, common sense, and evidence: a comment to the Andreas Grüntzig lecture 2015

In the old days, the Regius professors, white haired, distinguished and wise, rounded majestestetically with their fellows and staff. 1 Patients were presented and examined, and the eminent doctor reached final decisions. What he felt was standard, what he heard was diagnostic—in short: eminence-based medicine ruled. And without any doubt, eminent physicians had excellent clinical skills and great experience. They knew what they were doing, but their diagnoses were primarily based on visual observation and clinical examination—and thus not rarely false. Then, modern diagnostic tools were introduced. First, X-rays discovered by Wilhelm Röntgen (1845–1923) in 1895 allowed a glimpse to the heart, then after the Second World War ultrasound, and finally nuclear scans. CT and MRI provided better and better insight into the body. Even Regius professors had to learn that they might be wrong: the liver looked larger with ultrasound than clinically expected, the heart murmur was not necessarily confirmed by echocardiography, and the suspected influenza proved to be a bacterial infection upon laboratory examination. The eye, hands, and ears of clinical examination were out ruled more and more by technical developments and objective measures. Similarly, predictions were sometimes right, but often wrong: some patients lived longer than anticipated, while others died suddenly after an uneventful examination. Indeed, risk factors were completely neglected; when Franklin D. Roosevelt died unexpectedly of a cerebral haemorrhage, his personal physician Admiral Ross McIntyre said ‘ Came out of blue sky !’ The fact that his blood pressure had steadily risen during his presidency and had reached exorbitant levels of 310/190 mmHg, had not disturbed the prominent doctor. 2 Even in the 1980s, Michael Oliver, a distinguished professor at the University of Edinburgh and knighted by the Queen, was convinced that lowering cholesterol would cause depression, suicide, and accidents. He wrote in 1981: ‘It is probably of little value to reduce raised serum cholesterol concentrations in patients with overt IHD … ’. 3 Even surgeons, physicians with a known high self-esteem, were not much better: Prof. Theodor Billroth (1829–1894), chairman of surgery in Zurich and later in Vienna, said that any surgeon who would dare to touch the heart would lose the respect of his colleagues. And indeed, Werner Forssman (1904–1979), Nobel awardee of 1956, was fired by his boss, then the famous surgeon Professor Ferdinand Sauerbruch (1875–1951) in Berlin, after he had published that he had catheterized his own heart without any adverse effects. 4 In short, the eminent professors and surgeons impressed their fellow colleagues by their manual skills and courage, but they were often wrong. What is common sense or what the Germans call ‘ Gesunder Menschenverstand ’ ( healthy human reasoning )? The expression was first used by Thomas Paine in 1776 in his pamphlet Common Sense5 in which at the beginning of the American Revolution he encouraged common people in the Colonies to fight for an egalitarian government. Thus, common sense originally stood for the fundamental ability of every citizen to perceive, understand, and judge things that are shared by their fellow citizens without any doubt—in short, the basis of democracy. Can we utilize common sense also in medicine and science? Are there obvious things that do not require extensive proof? Well indeed, as pointed out by Bernard Meier in his review, 6 we hardly need a randomized study on the usefulness of parachutes during free fall nor do we have any doubt that defibrillation saves lives without randomized proof. But we can be deadly wrong with the best intentions: For instance, in the 1970s, ventricular ectopic beats were considered precursors of sudden cardiac death (SCD), until the CAST trial 7 and the SWORD trial 8 using antiarrhythmic drugs such as encainide, flecainide, moricizin, or d -sotalol, respectively, found an increased mortality rather than decreased mortality in spite of effective suppression of ventricular ectopic beats. Similarly, in heart failure, inotropes or phosphodiesterase inhibitors improved haemodynamics and exercise performance, and the patients felt great, but their mortality was increased. 9 Thus, against common believes, the paradigm of stimulating the heart was falsified, while the concept of unloading it proved effective. 10 We owe these insights to Sir Austin Bradford Hill (1897–1991), an English epidemiologist and statistician, who pioneered the randomized clinical trial and with Sir Richard Doll discovered the association of smoking with lung cancer. At the time, tuberculosis was the disease of the day and, with the advent of streptomycin, a completely new and promising remedy seemed at hand. But Hill wanted to prove efficacy beyond any doubt and pioneered the randomized clinical trail. 11 To that end, he enrolled patients aged between 15 and 30 years with acute progressive bilateral pulmonary tuberculosis of recent origin, bacteriologically proven and unsuitable for the then used best treatment. Both the streptomycin and control groups would receive the standard treatment for this type of disease—bed rest (as described in Thomas Manns famous novel The Magic Mountain12 ) and if necessary collapse therapy of the affected lung. As he reported in 1948 in his seminal paper in the British Medical Journal , 4 patients (or 7%) died in the streptomycin group and 14 (or 27%) in the control group. He concluded from these results: ‘The difference between the two series is statistically significant; the probability of it occurring by chance is less than one in a hundred.’ 13 From there on, evidence-based medicine was born and stimulated thousands of trials in all fields of cardiology and beyond—and indeed his concept became the standard of modern clinical science. Now, you may say: I knew this prior to this trial; myobacteria are the cause of tuberculosis and streptomycin kills them—so what? Well, did we really know for sure that streptomycin was better than high altitude air? Did we know whether streptomycin was safe? Certainly not. Ever since, therefore, we hardly dare to say ‘ This is my clinical experience ’ or ‘ I believe this makes sense ’—we rather say, ‘we have to await the results of future trials’ or ‘ in the absence of evidence I tend to this or that ’. In this issue of the European Heart Journal Bernard Meier, an eminent interventional cardiologist and trainee of Andreas R. Grüntzig (1939–1985), takes an opposite position. 6 He rightly reminds us that real life and science do not necessarily meet in interventional cardiology and in fact in medicine at large. And indeed, nobody would argue that in real life scientific evidence is not always followed in daily practice in spite of detailed ESC Guidelines for stable coronary artery disease, 14 revascularization, 15 NSTEM, 16 STEMI 17 among others. There are many reasons for that discrepancy: first, some colleagues may work in a healthcare system that does not have the resources to follow the guidelines. Second, novel evidence may have challenged guidelines and physicians may rightly deroute from their recommendations. Third, there are less convincing reasons: real life and science may not meet due to inappropriate financial incentives, because recommendations restrict certain professional activities or because certain colleagues question the findings on which recommendations are based. Finally, we have to reach decisions under many circumstances without available evidence. Indeed, even in cardiology with its large evidence base, only a minority (around 10–15%) of all medical decisions are truly evidence-based at level A 18 —thus, we still have to rely on common sense. But Bernard Meier goes beyond that. He argues that we should not always ask for the best evidence as some medical decisions are obvious. Does it make sense to prove the effectiveness and safety of TAVI in each age and every risk group? Is it not obvious that the procedure is safe and effective based on what we already know? Can we extrapolate from what we know to other patient populations, in short, use common sense? The eminent Henry Kissinger, now 92, the former secretary of state, has a clear opinion about TAVI: indeed, he described the procedure as easier and less debilitating than the open-heart bypass surgery he had previously. ‘There's no comparison.’ 19 But it is not the patient's view that is under consideration here: Bernard Meier's position is obviously more than just eminence-based as he accepts the basic evidence base, but extrapolates from it to other closely related patient groups with good reasoning. Indeed, trials expose patients to a certain risk, cost a lot of money, and delay the use of novel technologies and in this very case the trials revealed what common sense expected. Another example are interventions for conditions with a relatively low event rate like stroke in patients with a patent foramen ovale. Do we need a trial with 30 000 patients over 10 years to prove what is obvious? Is not it already convincing to close the defect, if after exclusion of any other cause in a young patient with a stroke a patent foramen ovale is found? Beyond any doubt, in experienced hands the procedure is safe and finished within half an hour. However, the data base is less convincing. Indeed, each of the individual trials only provided a trend towards a benefit, while meta-analyses reached the level of significance. 20 One of the reasons why all trials are underpowered is also the enthusiasm of interventional cardiologists to perform novel procedures as they receive C.E. mark and reimbursement by the health authorities rather than to enrol patients undergoing novel procedures initially into randomized trials—an unfortunate aspect that we all should remember. Without any doubt, evidence-based medicine as it is practised today has also its downsides: first, it is short-sighted—most trials last for 3–5 years only. However, a 45-year-old patient with an LDL-cholesterol of 3.8 mmol/L is primarily not interested in the next 5 years, but in his lifetime risk. 21 Can we extrapolate from 5 to 30 years? We might not, but we must in clinical practice. Short follow-ups also might overestimate the long-term safety of currently used TAVI valves. Secondly, most trials recruit only a very small minority of patients seen in everyday practice, which limits the generalizability of their findings. Although large real-world registries might be helpful in this context, this remains a limitation of today′s data base. Finally, trials may not be well performed; a most recent example is Symplicity HTN-3. 22 Although double blinded and with sham controls, it is obvious from the supplemental data that only a minority of the patients had convincing evidence of multiple ablations. 23 Indeed, a sub-analysis on the effects of the number of ablations on blood pressure reduction confirmed the effectiveness of renal nerve ablation in the subgroup with 12 or more ablations. 24 Nobody is perfect, neither is evidence-based medicine. The buttom line is that we need it all. Eminence reflects experience and skills of excellent physicians, common sense—in spite of its obvious downsides in scientific discovery—is indispensable in everyday practice, but evidence must remain our lighthouse guiding eventually the management of our patients. How much evidence we really need in each instance is indeed worth a discussion. Bernard Meiers ESC Grüntzig Lecture—although provocative and controversial—reminds us of these facts. The author reports not financial conflicts related to this editorial but acknowledges that he has trained with Bernard Meier, highly respects him and indeed considers him a friend.