Thrombolysis for Acute Myocardial Infarction: Drug Review

David K. Cundiff

Disclosures
In This Article

Factoring Faith, Placebo Effect, Reassurance, Emotional Stress

Sir William Osler elegantly described the power of the patient's faith in the healing process:

Faith in our drugs and methods is the great stock in trade of the profession... While we doctors often overlook or are ignorant of our own faith cures, we are just a wee bit too sensitive about those performed outside our ranks... Faith in the gods or saints cures one, faith in little pills another, hypnotic suggestion a third, faith in a plain common doctor a fourth... The faith with which we work...has its limitations...but such as we find it, faith is the most precious commodity without which we should be very badly off.[28]

These words uttered in 1901 relate directly to studies of thrombolytics for AMI.

In GISSI-1 and 2 other major thrombolysis trials, the investigators did not require an informed consent of the patients because of "the acuity of the clinical situation." Therefore, the investigators knew and were obligated to tell their patients if asked which ones received the experimental drug and which served as the controls.

This absence of informed consent and blinding raised the possibility that some of the patients who were told that they received the active experimental drug survived because of faith in the treatment. On the other hand, some patients who found that they did not receive the study drug may have died due to an adverse psychological reaction to the news. Confidence in the new "clot buster" drug, perhaps fostered by caring doctors and nurses, may have been the difference between life and death in enough patients (1% of the participants or 2% of those receiving active treatment) to make the result a statistically significant outcome favoring drug treatment. The investigators kept no data about how many patients in each group learned about the study and whether they did or did not receive the drug.

In the double-blinded studies in which physicians obtained informed consent, the various side effects of the thrombolytic drugs (eg, chills, fever, allergic reactions, minor bleeding or bruising, hypotension) undoubtedly alerted some doctors and patients to guess who was randomized to the experimental thrombolytic medications. This may have slightly improved survival outcomes again by the power of faith in the treatment. One of the main reasons that drug studies and other therapeutic trials should be double-blinded if possible is because of the influence of the patient's faith in the treatment in altering outcomes. In the case of the randomized studies, instilling AMI patients and their doctors with faith that thrombolytics work may have had the power to save the lives of enough patients to give the results statistical significance favoring thrombolysis.

The "early hazard" in the thrombolysis vs control studies could be consistent with complications of thrombolysis causing early mortality followed by a slight benefit or detriment in survival caused by psychological factors associated with the patient knowing that he/she was or was not receiving the experimental drug.

However, the use of thrombolytics comes also with an additional clinical price besides potentially fatal bleeding complications. In most countries where physicians prescribe thrombolytics, a doctor must discuss the pros and cons or risks and benefits of any treatment being proposed to a patient. A person with chest pain, being seen in an emergency room, would naturally fear for his/her life. Consequently, when the doctor diagnoses AMI and then recommends thrombolytic therapy because it increases chances for survival by 1/50, albeit with a small risk of fatal and nonfatal brain hemorrhage and other complications, most patients would have additional major stress.

Many patients hearing the odds of dying with and without thrombolytic therapy and the risks of fatal and other side effects of the therapy would ask for the advice of a trusted relative or, perhaps, the primary care doctor. However, the urgency of beginning thrombolytic treatment as soon as possible, preferably within 1 hour of symptoms, would often preclude getting outside advice. This may create additional anxiety just when reassurance, psychological support, and a tranquil atmosphere are most important aspects of the therapy to optimize survival. The effect on survival of the stress of deciding about thrombolysis and faith in the treatment will probably never be known because of the difficulty of measuring faith and stress. However, it is an issue that should be considered in future studies.

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