For fellows: the trials and tribulations of evidence-based cardiology

How can one keep up with the data?

Among specialties in internal medicine, cardiology is perhaps the most evidence-based, with new trial acronyms published weekly. It is one of the inherent qualities of modern-day cardiology that turns resident physicians either on or off to the field. Many fellows deeply embrace the numerous clinical trials available in the literature, and many feel overwhelmed by it.

The sheer quantity of data available in the present era of megatrials is overwhelming. How does one keep up with the data and retain the information about a critically analyzed study one month from now? How can one reconcile the disparate findings of A to Z with PROVE IT? What were the inclusion criteria in COMPANION compared to CARE-HF?

Three facets to learning

Roderick Tung

I believe that there are three facets to learning cardiology in fellowship: 1) textbook information, eg, y descent behavior in tamponade vs. constriction; 2) hands-on proficiency in procedures, eg, TEE and catheterization; and 3) evidence-based knowledge for application in clinical practice.

Textbook information is essentially static and is readily available in the form of Braunwald or board review books, but is also, perhaps, the most difficult type of learning to initiate and maintain among fellows.

Hands-on proficiency comes with repetition and good clinical instruction by attendings and senior fellows. I chose my fellowship specifically because of the high volume of catheterization, nuclear stress tests and echocardiography at our institution.

Keeping up with evidence-based cardiology has been greatly simplified by the Internet.

During my residency, I found it very helpful to synthesize trials into the various areas of cardiology and make one summary PowerPoint slide for each trial, with emphasis on historical trials. Data that are published during one’s medical training are much easier to retain than those published decades ago. The data are much more approachable when each trial in categorized into clinical scenarios, ie, clopidogrel in STEMI vs NSTEMI vs. PCI.

Many patients encountered in real-world clinical practice would be ineligible for clinical trials, and most composite endpoints are driven by the least clinically relevant event. In addition, many studies produce conflicting results. Were the patient characteristics in the PEACE trial that different from those in HOPE and EUROPA to account for lack of benefit from ACE inhibition?

There is also a strong tendency for clinicians to utilize the availability heuristic, in which the freshest and most retrievable piece of information learned is applied more frequently. For example, the number of patients given bicarbonate solution prior to cardiac catheterization dramatically increased across the nation based on the behavior of a mere 119 patients in one prospective study published in JAMA.

During my residency, patients received B vitamins and folate after PCI because of the restenosis benefits suggested by the Swiss Heart Study. Three years later, it appears that the homocysteine hypothesis is dead, according to some, because of the NORVIT study, presented at the European Society of Cardiology Congress, which showed that vitamin B and folate replacement had a trend toward increased adverse events.

Where does the truth lie? As outlined by the ACC, recommendations can only be given level A evidence if supported by more than one randomized clinical trial. Practice patterns should not be abandoned based on a single negative study, but the availability heuristic is powerful.

The generation gap

An additional phenomenon universally experienced by fellows and housestaff is reconciling new data with “old-fashioned” physiologically-based practice by senior attendings. The boom of industry- sponsored megatrials took place primarily in the mid to late 1990s, with initial randomized trials such as ISIS-2 supporting routine aspirin use in MI published as recently as 1988.

Physicians trained prior to the evidence-based era put their emphasis on physical examination and treatments based on physiological principle. For better or worse, the enthusiasm for auscultating an S2 intensity or the timing of an midsystolic click has been largely tempered by the availability of portable echocardiography.

Moreover, treatments like renal-dose dopamine are still implemented based on physiologic principle although numerous data and meta-analyses have demonstrated lack of benefit for preventing renal deterioration. Numerous cardiologists still prefer rhythm management to rate control for atrial fibrillation even though RACE and AFFIRM demonstrated the equivalence of these two approaches.

While clinical trials are one method for getting closer to the scientific “truth,” they are limited by generalizability, variability in study design, and are often antiquated shortly after publication. In a recently published article by Ioannidis in JAMA, entitled “Contradicted and Initially Stronger Effects in Highly Cited Clinical Research,” 16% of studies analyzed were subsequently contradicted, an additional 16% had attenuated effects subsequently, and 24% remained unchallenged.

With knowledge of more data, it seems that the more we know, the more we know that we don’t know. One can only make the best decision in clinical practice based upon all of the available data at a given point in time.

In the end, medicine is truly an art as much as it is a science and the appreciation of this fact is one step closer to becoming a better physician.

Roderick Tung, MD, a fellow at Cedars-Sinai, is a member of Cardiology Today’s Fellows Advisory Board.