Aspirin: A Simple Drug with Another Indication?
It has been clear for some time that in appropriate circumstances, a simple aspirin a day can be a potent therapeutic agent. Potential uses include: acute cardiac ischemic syndromes (unstable angina, NSTEMI or STEMI) or strokes; the treatment of vascular risks in diabetic patients with hypertension1; and an effort to reduce the risk of colon cancer, to name a few. This simple and cheap agent can be surprisingly effective.
Just when I thought we had seen all of aspirin’s benefits, a recent study detailed the use of aspirin therapy in a sick cohort admitted for COPD exacerbations.2
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COPD Exacerbation
In Exacerbations of Obstructive Lung Disease Managed in United Kingdom Secondary Care (EXODUS), researchers followed 1343 individuals with spirometry-proven COPD from 2009 to 2011. All enrolled patients were admitted to the hospital with a COPD exacerbation and then separated into 2 groups for further study: those with and those without thrombocytosis (platelet count >400,000 mm3).
Acute thrombocytosis has previously been characterized as an “inflammatory marker,” suggesting that the presence of an elevated platelet count may represent a sicker, more complication-prone group of patients. In this study, 12% of patients reported thrombocytosis during a hospitalized COPD exacerbation, which was associated with a 12% mortality as compared to 5% in patients admitted without thrombocytosis. Furthermore, thrombocytosis also predicted an increased in-hospital mortality (2.37 times greater; P=0.005), as well as a 53% 1-year mortality (P=0.030).2
The patients with thrombocytosis during a hospitalized COPD exacerbation also manifested other signs of greater illness, including an increased incidence of acidosis, a greater need for noninvasive ventilation strategies, and higher white blood cell counts. Since aspirin has been prescribed in order to prevent platelet-driven vascular pathology, it was used in this trial in an effort to mitigate increased mortality in COPD in-patients with thrombocytosis. Now that is where the study data got more interesting.
Use of Apsirin
Aspirin in low doses (80 mg to 100 mg) taken by the high platelet-COPD exacerbation cohort decreased the risk of 1-year mortality by 37%.2 Although an educated guess may lead to a proposition that aspirin in this group was cardioprotective—that did not appear to be the case. Cardiovascular hospitalizations were not more common in the elevated platelet group, on anti-platelet therapy, and aspirin did not decrease cardiac mortality or hospitalizations from cardiac causes. So, why might aspirin be of benefit in the COPD exacerbation group with thrombocytosis?
It seems that aspirin-mediated reductions in mortality in COPD exacerbations with acute thrombocytosis might be a pleiotropic effect of aspirin. Remember that word pleiotropic, which has become commonplace in discussions of certain pharmacological agents (eg, statins and angiotensin-converting enzyme [ACE] inhibitors).
When statins are administered to patients undergoing vascular surgery, they decrease mortality. It has become clear that these benefits exceed simply lowering cholesterol. Namely, they represent other actions—anti-inflammatory in nature—and possibly plaque stabilizing. When ACE inhibitors are given to patients with proteinuria, they lower urine protein excretion and protect kidneys in addition to lowering blood pressure. Similarly, aspirin in COPD exacerbations with additional inflammatory or severity markers—in this instance, an elevated platelet count—leads to an incomplete understanding of benefits (pleiotropic ones), which possibly dampens certain aspects of inflammation.
Although the data is preliminary, aspirin may have benefits in the setting of COPD exacerbations in a specific, higher risk cohort—one with acute thrombocytosis. Apparently, this old drug keeps adding to its resume!
Gregory W. Rutecki, MD, is a physician at the National Consult Service at the Cleveland Clinic. He is also a member of the editorial board of Consultant. Dr Rutecki reports that he has no relevant financial relationships to disclose.
References:
1. Kjeldsen S, Hedner T, Jamerson K, et al. Hypertension optimum treatment (HOT) study. Hypertension. 1998;31:1014-1020.
2. Harrison MT, Short P, Williamson PA. Thrombocytosis is associated with increased short and long-term mortality after exacerbations of chronic obstructive pulmonary disease: a role for anti-platelet therapy. Thorax. 2014 Apr 7. [epub ahead of print]
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