Thursday, January 3, 2019

Alcohol and your health: Is none better than a little?

I was called to your room in the middle of an overnight shift. There you were, breathing quickly, neck veins bulging and oxygen levels hovering despite the mask on your face. I placed my stethoscope on your back and listened to the cacophony of air struggling to make its way through your worsening pneumonia.
“We’re going to place a tube down your throat to help you breathe,” I told you.
Your eyes were pleading, scared. “We’ll put you to sleep. It’ll help you breathe more comfortably. Okay?”
You nodded. You had already told the doctors who cared for you during the day that if your breathing worsened, you would agree to intubation to allow more time to treat your pneumonia. So I called for the anesthesiologists. Minutes later, you were sedated and intubated, silenced — maybe forever.
I thought about you recently, when I read a poignant Perspective in JAMA Internal Medicine: “Saving a Death When We Cannot Save a Life in the Intensive Care Unit.” In this piece, critical care doctor Michael Wilson relates the story of a woman in the ICU who was electively intubated for a procedure and then died, without ever having had the opportunity for her loved ones to say goodbye.
Fueled by his feelings of regret over this and similar cases, Wilson argues for a different approach to intubation, which he likens to the talk a parent has with a child who is going off to war. Of course, these parents hope their children will come back safely, but they are given the chance to say what they want to say — knowing the conversation might be their last. Wilson suggests that we might build a similar pause into our protocols before intubation, lest we unwittingly deprive our patients of the opportunity for a final exchange with their loved ones. “Stealing the opportunity for meaningful last words is precisely the kind of avoidable complication that ought to be visible to us in the ICU,” Wilson writes. “My intubation checklist now includes this step.” In doing so, Wilson suggests that we might be able to “save a death” even if we are ultimately unable to save a life.
Reading this piece, I’m left with the image of Wilson’s patients — both the one who never had the chance to say goodbye, and another woman he describes who was given the chance to say “I love you” to her husband — and also of my own patients. It is too easy, in the heat of the moment, to forget that this patient before us is a person. How many times have I decided on intubation, ordered the appropriate medications, prepared for complications, but not taken pause to allow my patient to talk to a loved one?
I only took care of you for the night, as the physician on call. Though I remember your face, I do not remember your name and I don’t know what happened to you. Maybe the breathing tube came out in a day or two, and you were able to talk to your family once again. Or maybe it did not. Maybe your pneumonia worsened and you died, there in our ICU. It has been months since that night, and I can’t know. But I do wish, now, that I had paused and given you that chance. Well, it seems as though not even a week can go by without more data on aspirin! I recently reviewed the ARRIVE trial and the implications for primary prevention — that is, trying to prevent heart attacks and strokes in otherwise healthy people. Since then, yet another large clinical trial — the ASPREE study — has come out questioning the use of aspirin in primary prevention. Three articles pertaining to this trial were published in the prestigious New England Journal of Medicine, which is an unusual degree of coverage for one trial and highlights its immediate relevance to clinical practice.
Aspirin still strongly indicated for secondary prevention

Nothing about any of the new aspirin data, including ASPREE, pertains to secondary prevention, which refers to use of aspirin in patients with established cardiovascular disease. Examples include a prior heart attack or certain types of stroke, previous stents or bypass surgery, and symptomatic angina or peripheral artery disease. In general, in patients with a history of these conditions, the benefits of aspirin in reducing cardiovascular problems outweigh the risks. Chief among these is a very small risk of bleeding in the brain, and a small risk of life-threatening bleeding from the stomach.
ASPREE study suggests no benefit from aspirin in primary prevention

ASPREE randomized 19,114 healthy people 70 or over (65 or over for African Americans and Hispanics) to receive either 100 milligrams of enteric-coated aspirin or placebo. After an average of almost five years, there was no significant difference in the rate of fatal coronary heart disease, heart attack, stroke, or hospitalization for heart failure. There was a significant 38% increase in major bleeding with aspirin, though the actual rates were low. The serious bleeding included bleeding into the head, which can lead to death or disability. Again, the actual rates were very low, but they are still a concern when thinking of the millions of patients to whom the ASPREE results apply.

Rates of dementia were also examined, and again, there was no benefit of aspirin. Quite unexpectedly, there was a significantly higher rate of death in the patients taking aspirin. This had not been seen in prior primary prevention trials of aspirin, so this isolated finding needs to be viewed cautiously. Still, with no benefits, increased bleeding, and higher mortality, at least in this population of older healthy people, aspirin should no longer be routinely recommended.

Another unexpected finding in ASPREE was a significantly higher rate of cancer-related death in the people randomized to aspirin. The prior thinking had been that aspirin might actually prevent colon cancer, though generally after many more years of being on aspirin. The ASPREE trial was terminated early due to lack of any apparent benefits. And even though five years is a relatively long period of follow-up, it may not have been long enough to find a benefit on cancer. Thus, the increase in cancer deaths may be a false finding. Nevertheless, the overall picture from this trial is not a compelling one for aspirin use for prevention of either cardiac or cancer deaths.
Should healthy people take a daily aspirin?

In general, the answer seems to be no — at least not without first consulting your physician. Despite being available over the counter and very inexpensive, aspirin can cause serious side effects, including bleeding. This risk goes up with age. So, even though it seems like a trivial decision, if you are healthy with no history of cardiovascular problems, don’t just start taking aspirin on your own.

However, there are likely select healthy patients who have a very high risk of heart attack based on current smoking, family history of premature heart attacks, or very elevated cholesterol with intolerance to statins, for example, who might benefit. Therefore, the decision to start aspirin should involve a detailed discussion with your physician as part of an overall strategy to reduce cardiovascular risk. If you are already taking aspirin for primary prevention, it would be a good idea to meet with your physician and see if you might be better off stopping. Surprisingly, one of the most controversial areas in preventive medicine is whether or not people without known cardiovascular disease should take a daily aspirin for primary prevention. That is, should you take aspirin to reduce the risk of heart attack, unstable angina, stroke, transient ischemic attack, or death from cardiovascular causes? You would think that we would know the answer by now for a medicine as commonly used as aspirin.
Aspirin has unquestioned benefit for secondary prevention

Before considering the impact of aspirin in people without cardiovascular disease, it is first important to clarify uses for aspirin that are not up for debate. In people who have had a heart attack or certain types of stroke, the use of aspirin to prevent a second event — potentially a fatal one — is firmly established. These uses of aspirin are called secondary prevention. Similarly, in people who have had stents or bypass surgery, lifelong daily aspirin is typically warranted. While there is a very small risk that aspirin can cause bleeding in the brain, and a small risk it can cause life-threatening bleeding such as from the stomach, in general the risks are worth it in the setting of secondary prevention.
ARRIVE study suggests no benefit from aspirin in primary prevention

Primary prevention refers to trying to prevent the first event, such as heart attack or stroke (or dying from these causes). In this setting, the actual risks of a cardiovascular event are much lower, though the bleeding risks persist. Therefore, the margin of potential benefit is much more narrow.

Recently in Munich, at the European Society of Cardiology conference — now the world’s largest cardiology meeting — important results pertaining to aspirin in primary prevention arrived in the form of the ARRIVE trial. This clinical trial randomized over 12,000 patients to either 100 milligrams (mg) of coated aspirin daily or to a placebo (a blank). Overall, after an average of five years of following these patients, the trial did not show a significant benefit for aspirin, though there was a significant increase in gastrointestinal bleeding. There were no significant differences in the rates of deaths, heart attacks, or strokes.

Digging a bit more deeply into the results, the enrolled patients ended up being at much lower cardiovascular risk than the researchers had intended. Thus, it is possible that in a higher-risk population with a greater rate of cardiovascular events, aspirin may have been useful. Furthermore, many patients stopped taking their aspirin, diluting the potential to see a benefit. In patients who actually took their assigned aspirin, there was in fact a significant reduction in the rates of heart attack. However, these types of “on treatment” analyses should be viewed cautiously, as it would of course exclude patients who had bleeding complications or other side effects that may have led to aspirin discontinuation.

Aspirin is not currently labeled for use in primary prevention. In fact, based on trials prior to ARRIVE, the US FDA did not feel the data were robust enough to give aspirin this indication for use. It seems unlikely that they will change that opinion on the basis of ARRIVE.

One notable group excluded from ARRIVE was people with diabetes. A separate randomized trial called ASCEND was presented at the European Society of Cardiology conference. This study did find a significant reduction in adverse cardiovascular outcomes with daily aspirin in people with diabetes, though there was also a similar magnitude of increased major bleeding. Still, many people would rather be hospitalized for bleeding and get a transfusion versus being hospitalized for a heart attack that causes permanent damage to the heart. Others may not see much difference between the two types of events and may prefer not to take an additional medication.
Should you take a daily aspirin?

So, where does this leave the average person who is worried about a heart attack and wants to do everything they can to reduce that risk? Again, for people with cardiovascular disease — secondary prevention — nothing about ARRIVE pertains to you. For otherwise healthy people at elevated risk for heart disease or stroke, make sure not to smoke, maintain a healthy weight and diet, and control elevated blood pressure and cholesterol with medications if needed. If you have diabetes, make sure that is controlled with diet and medications if diet alone is insufficient.

The decision to start daily aspirin in otherwise healthy people is quite complex, with potential benefits and actual risks that on average are rather similar. Serious bleeding may occur. Online risk calculators (such as might be somewhat useful in more objectively calculating the degree of cardiovascular risk. However, in the absence of diabetes, most otherwise healthy people should probably not be taking a daily aspirin to prevent heart attacks.

In the future, if randomized evidence supports it, imaging tests that gauge the degree of silent atherosclerosis (plaque buildup in the arteries that is not causing symptoms) may help decide if a patient should be reclassified from primary to secondary prevention. Other analyses from the large ASPREE trial are ongoing, should report soon, and may further tip the scales. For now, healthy people without atherosclerosis should not just take aspirin on their own without consulting their doctor first.

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