Etiology

New use of atypical antipsychotics was linked to acute kidney injury and all-cause mortality at 90 days Clinical impact ratings:

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Question In older patients, is new use of atypical antipsychotic drugs (AAPs) associated with acute kidney injury (AKI) and other adverse outcomes?

Hwang YJ, Dixon SN, Reiss JP, et al. Atypical antipsychotic drugs and the risk for acute kidney injury and other adverse outcomes in older adults: a population-based cohort study. Ann Intern Med. 2014;161:242-8.

多多多多多多夞 increased risk for all-cause mortality, pneumonia, AMI, hypotension, ventricular arrhythmias, and acute urinary retention (Table).

Conclusion

Methods

In older patients, new use of atypical antipsychotic drugs was associated with acute kidney injury and mortality at 90 days.

Design: Population-based cohort study using data from 5 linked administrative databases; follow-up was 90 days.

Source of funding: Institute for Clinical Evaluative Sciences Western site.

Setting: Ontario, Canada.

For correspondence: Dr. A.X. Garg, London Health Sciences Centre, London, ON, Canada. E-mail [email protected]. 

Patients: 97 777 outpatients ≥ 66 years of age (mean age 81 y, 64% women) who received a new prescription for an oral AAP (risperidone, n = 44 707; quetiapine, n = 34 498; or olanzapine, n = 18 572) and could be matched with a patient not using AAPs based on age, sex, residential status (community or longterm care), comorbid conditions, availability of serum creatinine data, and propensity score (comprised of 91 variables) for new AAP use. New drug users with prescriptions for > 1 type of AAP on the index date (date of first AAP prescription between Jun 2003 and Dec 2011) and nonusers who did not have an outpatient prescription ≤ 90 days before their randomly assigned index date were excluded. In both groups, exclusion criteria were end-stage renal disease, hospital discharge ≤ 2 days before the index date, or prescription of any antipsychotic drug ≤ 180 days before the index date. Risk factor: New prescription for an AAP. Outcomes: Hospitalization for AKI identified by International Classification of Diseases, 10th revision (ICD-10), codes or, for patients with available laboratory data, ≥ 27 μmol/L (≥ 0.31 mg/ dL) or ≥ 50% increase in serum creatinine level from baseline. Other outcomes were all-cause mortality and hospitalization for pneumonia, acute myocardial infarction (AMI), hypotension, acute urinary retention, ventricular arrhythmia, and rhabdomyolysis or the neuroleptic malignant syndrome.

Commentary Evidence-based guidelines caution against use of AAPs for treatment of behavioral disturbances in dementia (1). Randomized trials consistently find that AAPs have only modest benefit at the price of increased mortality and morbidity (2). Nevertheless, off-label use of AAPs to manage agitation and behavioral disturbance in dementia remains a common practice (3), which no doubt reflects clinician and caregiver response to evident distress and potentially dangerous agitation. Hwang and colleagues examined a range of adverse outcomes in almost 100 000 older outpatients starting treatment with AAPs compared with a similar sample of nonusers. As expected, those treated with AAPs had greater overall mortality and higher risk for pneumonia. The new findings include increased risk for AKI as well as hypotension and urinary retention (possible mechanisms for kidney injury).

Randomized trials provide the strongest evidence about safety or adverse effects of AAPs. With observational studies, we can never be completely confident that matching or adjustment adequately accounts for unmeasured risk factors or confounders. For example, the acute agitation that prompts an AAP prescription may be triggered by an underlying illness that is the true cause of increased mortality. On the other hand, large observational studies provide precision to examine more specific or less Main result common outcomes. A closer look at such outcomes (e.g., AKI) Use versus nonuse of AAPs was associated with increased risk can address questions about which patient groups are at higher for hospitalization for AKI assessed using ICD-10 codes (Table) risk, what signs of risk should be monitored, and the pathways or with serum creatinine data (n = 3592, 5.5% vs 3.3%, odds or mechanisms by which AAPs increase overall mortality. Anratio 1.70, 95% CI 1.22 to 2.38). AAPs were associated with swers to these questions could inform research about safer alternatives and guide clinician and caregiver decisions about more selective use of the unsatisfactory treatments currently available. Association between new use of atypical antipsychotic drugs (AAPs) and adverse outcomes in older adults* Gregory Simon, MD, MPH Group Health Research Institute Outcomes† Event rates At 90 d after prescription date Seattle, Washington, USA AAPs

No AAPs

Acute kidney injury

1.02%

0.62%

Adjusted OR (95% CI)‡ 1.73 (1.55 to 1.92)

References

All-cause mortality

6.82%

3.05%

2.39 (2.28 to 2.50)

Pneumonia

1.73%

1.16%

1.50 (1.39 to 1.62)

Acute myocardial infarction

0.67%

0.50%

1.36 (1.20 to 1.53)

Hypotension

0.39%

0.22%

1.91 (1.60 to 2.28)

1. Maglione M, Ruelaz Maher A, Hu J, et al. Off-label use of atypical antipsychotics: an update. Comparative Effectiveness Review No. 43. Rockville, MD: Agency for Healthcare Research and Quality. September 2011. www.effectivehealthcare.ahrq .gov/ehc/products/150/778/CER43_Off-LabelAntipsychotics _20110928.pdf (accessed 23 Dec 2014).

Acute urinary retention

0.34%

0.17%

1.98 (1.63 to 2.40)

Ventricular arrhythmia

0.22%

0.15%

1.47 (1.18 to 1.82)

Rhabdomyolysis or the neuroleptic malignant syndrome

0.10%

0.07%

1.36 (0.96 to 1.92)

*OR = odds ratio; CI defined in Glossary. †Outcomes were hospitalization events except for all-cause mortality. ‡OR was interpreted as a risk ratio by the authors and adjusted for local health integration network (geographically defined health authorities in Ontario).

姝 2015 American College of Physicians JC12 ACP Journal Club Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/27/2015

2. Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA. 2005;294:193443. 3. Alexander GC, Gallagher SA, Mascola A, Moloney RM, Stafford RS. Increasing off-label use of antipsychotic medications in the United States, 1995-2008. Pharmacoepidemiol Drug Saf. 2011;20:177-84.

Annals of Internal Medicine

17 February 2015

ACP Journal Club: new use of atypical antipsychotics was linked to acute kidney injury and all-cause mortality at 90 days.

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