Faculty Peer Reviewed
One hot topic making news this week is government spending on substance abuse, addiction and its consequences, both medical and legal. As reported in The New York Times, the National Center on Addiction and Substance Abuse issued a report estimating that $468 billion was dispensed in 2005 for smoking, alcohol abuse and illegal drugs, with the majority of this huge financial burden allocated for direct health care costs associated with lung disease, cirrhosis and overdose. This “stunning misallocation of resources,” according to Joseph Califano, Jr., has gained media attention, leading to commentary about the need for better preventive measures and treatment programs, which ultimately could save money. Perhaps with the nation’s current focus on saving money, politicians will take heed and focus on more preventive strategies.
But enough about money! This week in the journals, several studies evaluated commonly prescribed medications and questioned their use in general practice. Intrigued? Read on…
Most of us have been guilty of prescribing proton pump inhibitors (PPIs) to our hospitalized patients without prudently assessing their need and often disregarding the actual indications for their use. Perhaps the article titled “Acid-Suppressive Medication Use and the Risk for Hospital-Acquired Pneumonia,” published in this week’s JAMA, will motivate us to reconsider prescribing PPIs without giving due consideration to potential adverse events.
According to the study, an estimated 40-70% of medical inpatients are treated with either a PPI or H2-receptor antagonist during hospitalization; approximately 50% of the patients are newly started on these medications, and nearly 50% of these patients are discharged on a PPI. While several outpatient studies suggest an increased risk of community-acquired pneumonia in patients receiving acid-suppressive medications, no large-scale studies exist to determine the association between acid-suppressive medications and hospital-acquired pneumonia. Herzig, et al, conducted a large, prospective cohort study from January 2004 through December 2007, including patients over the age of 18 (median age 54) admitted to the hospital for at least 3 days. Excluded from this study were all patients who spent any time in the ICU. The final cohort consisted of 63,878 admissions, of which 52% received either a PPI (83%) or H2-receptor antagonist (23%) during hospitalization. The primary outcome of hospital-acquired pneumonia occurred in 2219 admissions (3.5%). In the group of patients receiving acid-suppressive medications, there was a higher unadjusted incidence of hospital-acquired pneumonia compared to the unexposed group: 4.9% vs 2.0%, OR 2.6 (95% CI, 2.3-2.8). Additionally, there was a significant association for both aspiration pneumonia and non-aspiration pneumonia, with the diagnoses based on ICD-9 codes used at the time of hospitalization. After adjusting for potential confounders, the adjusted OR for hospital-acquired pneumonia in the group receiving acid-suppressive therapy was 1.3 (95% CI, 1.1-1.4). Interestingly, after adjustment, the association was significant only for PPI’s and not H2-receptor antagonists. Overall, the use of acid-suppressive medications, in particular PPIs, was associated with a 30% increased odds of developing hospital-acquired pneumonia. Given the estimated mortality rate of 18% for hospital-acquired pneumonia, these results are somewhat alarming. Thus, this study clearly emphasizes the need to closely examine our patient’s medication regimen at the time of hospitalization and determine if a PPI is truly warranted.
Another interesting topic focusing on medication administration is addressed in an article titled “Current Guidelines for Using Angiotensin-Converting Enzyme Inhibitors and Angiotensin II-Receptor Antagonists in Chronic Kidney Disease: Is the Evidence Relevant to Older Adults?” Estimates suggest that nearly half of adults in the general population age 70 or older have chronic kidney disease. Current literature demonstrates that ACE-inhibitors and ARBs have renoprotective properties in patients with CKD through their ability to decrease proteinuria. The study, recently published in The Annals, reviewed randomized controlled trials that included at least one group of participants receiving an ACE inhibitor or ARB, compared to placebo, and that also reported at least one pre-specified “renal outcome” (i.e. change in urinary protein, serum creatinine level, estimated GFR, etc.). The authors found that adults older than 70 are underrepresented in most trials used to establish the current U.S. practice guidelines for the use of ACE-inhibitors and ARBs in CKD; of the 27 trials reviewed, 76% either excluded or did not include participants over the age of 70. A notable exception is the ALLHAT study, with a mean age of 71 among trial participants with a reduced eGFR. Moreover, while most trials reviewed in this study included patients with diabetes and proteinuria, the authors determined that most elderly people with CKD do not have proteinuria (>85%) in spite of having a disproportionately reduced eGFR. The etiology of this discrepancy is multi-factorial and likely the result of the aging process on the kidneys. Thus, the current guidelines may not be as relevant to older populations compared to younger age groups, since the reduction in proteinuria is thought to comprise the primary renoprotective effect of ACE-inhibitors and ARBs. One limitation of this study is that it did not consider other potential therapeutic benefits of ACE-inhibitors or ARBs in this aging population, particularly cardiovascular effects. Given the potential adverse effects of these medications, perhaps the overall risks outweigh the benefits in the elderly population, among whom the progression of chronic kidney disease is often slow and typically not life- threatening.
This week in The Lancet, a meta-analysis attempts to tackle the controversy over aspirin (ASA) use in the primary prevention of vascular disease. According to the authors of this study, current guidelines recommend administering ASA as primary prevention to anyone with a moderate risk of CHD. In order to challenge the current guidelines, the authors conducted a collaborative meta-analysis of individual participant data to assess benefits versus risks of ASA as primary prevention in specific groups of study participants. They examined serious vascular events (MI, stroke, vascular death) and major bleeding complications in six primary prevention trials and sixteen secondary prevention trials that compared ASA with a control group. By using ASA in the primary prevention trials, there was an absolute risk reduction in serious vascular events of 0.07% per year, representing a 12% proportional reduction in these events, mostly by reducing non-fatal MI. Overall there was no significant difference between pre-specified subgroups; the same benefit was seen for men and women, as well as a similar benefit regardless of baseline risk of CHD. Interestingly, the proportional reduction in risk was similar in both the primary and secondary prevention trials; however, the absolute risk reduction in serious vascular events was significantly greater in the secondary prevention group: 1.49% per year. Aspirin use in the primary prevention trials also did not demonstrate a significant benefit on overall mortality. When evaluating adverse events, the major risk of extracranial bleed, in particular gastrointestinal bleeding, was increased in the primary prevention trials (0.10% vs 0.07% per year, RR 1.54). Based on the data, this study emphasizes several salient points about ASA use in primary vs. secondary prevention of vascular events. First, the absolute benefits of ASA in primary prevention are significantly less than in people with known CHD who use ASA as secondary prevention. Additionally, assessment of individual participants’ risk demonstrated a non-significant trend toward benefit in the proportional effects of ASA in people with very low, low, moderate or high risk of CHD. The proportional risk reduction of ASA in primary prevention also did not depend upon gender, age or CHD-associated risk factors. Statin use and a specific focus on diabetics without known CHD are two areas that previously published primary prevention trials did not carefully investigate. Thus, it appears as though the use of ASA in primary prevention is not as clear-cut as once assumed, with such a small absolute risk reduction in major vascular events and no significant trend in benefit when comparing baseline CHD risk. More studies looking at specific subgroups of patients, including those optimized on new and improved medical therapy, will hopefully expand our understanding of the role of aspirin in primary prevention.
Dr. Lambert is a 3rd year resident in internal medicine at NYU Medical Center.
Reviewed by Danise Schiliro-Chuang MD, Contributing Editor, Clinical Correlations
Herzig S, Howell M, Ngo L, et al. Acid suppressive medication use and the risk for hospital-Acquired pneumonia. The Journal of the American Medical Association. 2009;301: 2120-2128.
O’Hare A, Kaufman J, Covinsky K, et al. Current guidelines for using angiotensin-converting Enzyme inhibitors and angiotensin II-receptor antagonists in chronic kidney disease: is the evidence base relevant to older adults? Annals of Internal Medicine. 2009;150: 717-724.
Antithrombotic Trialists’ (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomized trials. The Lancet. 2009;373:1849-1860.