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Prognostic Effects of Selective Serotonin Reuptake Inhibitors in Patients With Coronary Artery Bypass Grafting
READERS’ COMMENTS Prognostic Effects of Selective Serotonin Reuptake Inhibitors in Patients With Coronary Artery Bypass Grafting Xiong and colleagues1 reported that the use of a selective serotonin reuptake inhibitor (SSRI) before coronary artery bypass grafting (CABG) was associated with a significantly excessive mortality rate of 61% and rehospitalization rate of 52%. However, the investigators misclassified the SSRI class drug. They included venlafaxine (a selective nonepinephrine reuptake inhibitors [SNRI] class drug) and clomipramine (a tetracyclic antidepressant class drug) in the SSRI group. Therefore, the title of the study is misleading. Differences may exist in the profiles and mortality between SSRI users and SNRI or tetracyclic antidepressant users.2 A separate analysis of the SSRI users (65% of all antidepressant use) and other antidepressant users (35% of all antidepressant use) would help identify whether SSRI drugs, depression itself, or the 2 together increased the adverse outcomes among patients undergoing CABG. Furthermore, the investigators did not adjust for socioeconomic status in the analysis—an important predictor of illness and prognosis. Low socioeconomic status is related to depression3 and its severity4 and a poor prognosis after CABG.5 Further analysis with additional adjustment for socioeconomic status of the 3 groups of non-SSRI use, SSRI use, and other antidepressant drug use may clarify the issue of the independent prognostic effects of SSRI use among patients undergoing CABG. Li Wei, PhD Ruoling Chen, PhD Ninewells Hospital and Medical School Dundee, Scotland 18 July 2006
*Letters (from the United States) concerning a particular article in The American Journal of Cardiology威 must be received within 2 months of the article’s publication, and should be limited (with rare exceptions) to 2 double-spaced typewritten pages. Two copies must be submitted.
1. Xiong GL, Jiang W, Clare R, Shaw LK, Smith PK, Mahaffey KW, O’Connor CM, Krishnan KR, Newby LK. Prognosis of patients taking selective serotonin reuptake inhibitors before coronary artery bypass grafting. Am J Cardiol 2006;98:42– 47. 2. Buckley NA, McManus PR. Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data. BMJ 2002;325:1332–1333. 3. Chen R, Wei L, Hu Z, Qin X, Copeland JRM, Hemingway H. Depression in older people in rural China. Arch Intern Med 2005;165:2019 – 2025. 4. Chen R, Hu Z, Qin X, Xu XC, Copeland JMR. A community-based study of depression in older people in Hefei, China—the GMS-AGECAT prevalence, case validation and socio-economic correlates. Int J Geriatr Psychiatry 2004;19:407– 413. 5. Ancona C, Agabiti N, Forastiere F, Arca M, Fusco D, Ferro S, Perucci CA. Coronary artery bypass graft surgery: socioeconomic inequalities in access and in 30 day mortality. A population-based study in Rome, Italy. J Epidemiol Community Health 2000;54:930 –935. doi:10.1016/j.amjcard.2006.07.012
The Need for a Systematic Review on the Safety Concerns of Nonopioid Analgesics We are pleased with the narrative review by Whelton1 that reminds the medical community of the well-described cautions associated with the use of selective cyclooxygenase-2-selective inhibitors and nonselective nonsteroidal antiinflammatory drugs (NSAIDs) in patients with (or at risk of) cardiovascular disease.1 We are concerned, however, that the lack of a comprehensive systematic literature review as the starting point for their report may have resulted in an unbalanced presentation of the risks and benefits of NSAID and acetaminophen use in this patient population. One concern with this report is that it fails to discuss the positive effects of NSAIDs in acute and long-term use. Abundant literature has documented the population-based cardioprotective benefits of aspirin and certain other NSAIDs. The evidence-based literautre has reported no increase in risk or a demonstrable decrease in risk of cardiac disease with both acute and chronic exposure to certian NSAIDs.2– 6 Of greater concern are the multiple references in their report to acetaminophen as a low- or no-risk analgesic alternative to NSAIDs. Acetaminophen is
0002-9149/06/$ – see front matter © 2006 Elsevier Inc. All rights reserved.
the drug most frequently associated with medication-related liver failure in the United States.7 The distribution and clearance of acetaminophen in patients with congestive heart failure is reduced, increasing the risk of toxicity or overdose.8 Consumption of acetaminophen has been associated with an increased odds ratio for a major cardiovascular event in women compared with aspirin, and acetaminophen has been reported to interfere with platelet aggregation.9,10 An equally grave oversight in this review is its failure to distinguish between acute and long-term exposure to analgesics. Systematic reviews recently performed by the United States Food and Drug Administration and the European Medicines Agency have affirmed the safety of NSAIDs given to treat acute pain.5,11 Systematic reviews of multimodal analgesia (i.e., providing an NSAID to decrease postoperative morphine requirements) have disclosed the clear benefit of such an approach.12 This broad observation has been specifically confirmed in the postcardiac surgical population.13–16 The systematic evaluation of the safety of NSAID use occasioned by the re-examination of cyclooxygenase-2-selective inhibitors must be accompanied by a clear, fresh look at the therapies proposed as alternatives. For example, the recommended dose of the only currently available intravenous acetaminophen formulation for administration in the acute setting is 1 g every 6 hours, a dosage level that has recently been shown in a short-term, randomized controlled trial to elevate serum alanine aminotransferase levels to ⬎3 times the upper limit of normal in 1/3 of healthy volunteers.17,18 Selection of an analgesic therapy, especially in at-risk patients as described in their report, requires a balanced, evidence-based review, not just of the safety of the medication of interest, but also of the relative toxicities of the recommended therapeutic alternatives, to support an optimal clinical recommendation. Robert D. Colucci, PharmD Daniel B. Carr, MD Curtis Wright IV, MD, MPH Jane L. Loescher, MS Cambridge, Massachusetts 25 July 2006
www.AJConline.org
*Letters (from the United States) concerning a particular article in The American Journal of Cardiology威 must be received within 2 months of the article’s publication, and should be limited (with rare exceptions) to 2 double-spaced typewritten pages. Two copies must be submitted.
1. Xiong GL, Jiang W, Clare R, Shaw LK, Smith PK, Mahaffey KW, O’Connor CM, Krishnan KR, Newby LK. Prognosis of patients taking selective serotonin reuptake inhibitors before coronary artery bypass grafting. Am J Cardiol 2006;98:42– 47. 2. Buckley NA, McManus PR. Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data. BMJ 2002;325:1332–1333. 3. Chen R, Wei L, Hu Z, Qin X, Copeland JRM, Hemingway H. Depression in older people in rural China. Arch Intern Med 2005;165:2019 – 2025. 4. Chen R, Hu Z, Qin X, Xu XC, Copeland JMR. A community-based study of depression in older people in Hefei, China—the GMS-AGECAT prevalence, case validation and socio-economic correlates. Int J Geriatr Psychiatry 2004;19:407– 413. 5. Ancona C, Agabiti N, Forastiere F, Arca M, Fusco D, Ferro S, Perucci CA. Coronary artery bypass graft surgery: socioeconomic inequalities in access and in 30 day mortality. A population-based study in Rome, Italy. J Epidemiol Community Health 2000;54:930 –935. doi:10.1016/j.amjcard.2006.07.012
The Need for a Systematic Review on the Safety Concerns of Nonopioid Analgesics We are pleased with the narrative review by Whelton1 that reminds the medical community of the well-described cautions associated with the use of selective cyclooxygenase-2-selective inhibitors and nonselective nonsteroidal antiinflammatory drugs (NSAIDs) in patients with (or at risk of) cardiovascular disease.1 We are concerned, however, that the lack of a comprehensive systematic literature review as the starting point for their report may have resulted in an unbalanced presentation of the risks and benefits of NSAID and acetaminophen use in this patient population. One concern with this report is that it fails to discuss the positive effects of NSAIDs in acute and long-term use. Abundant literature has documented the population-based cardioprotective benefits of aspirin and certain other NSAIDs. The evidence-based literautre has reported no increase in risk or a demonstrable decrease in risk of cardiac disease with both acute and chronic exposure to certian NSAIDs.2– 6 Of greater concern are the multiple references in their report to acetaminophen as a low- or no-risk analgesic alternative to NSAIDs. Acetaminophen is
0002-9149/06/$ – see front matter © 2006 Elsevier Inc. All rights reserved.
the drug most frequently associated with medication-related liver failure in the United States.7 The distribution and clearance of acetaminophen in patients with congestive heart failure is reduced, increasing the risk of toxicity or overdose.8 Consumption of acetaminophen has been associated with an increased odds ratio for a major cardiovascular event in women compared with aspirin, and acetaminophen has been reported to interfere with platelet aggregation.9,10 An equally grave oversight in this review is its failure to distinguish between acute and long-term exposure to analgesics. Systematic reviews recently performed by the United States Food and Drug Administration and the European Medicines Agency have affirmed the safety of NSAIDs given to treat acute pain.5,11 Systematic reviews of multimodal analgesia (i.e., providing an NSAID to decrease postoperative morphine requirements) have disclosed the clear benefit of such an approach.12 This broad observation has been specifically confirmed in the postcardiac surgical population.13–16 The systematic evaluation of the safety of NSAID use occasioned by the re-examination of cyclooxygenase-2-selective inhibitors must be accompanied by a clear, fresh look at the therapies proposed as alternatives. For example, the recommended dose of the only currently available intravenous acetaminophen formulation for administration in the acute setting is 1 g every 6 hours, a dosage level that has recently been shown in a short-term, randomized controlled trial to elevate serum alanine aminotransferase levels to ⬎3 times the upper limit of normal in 1/3 of healthy volunteers.17,18 Selection of an analgesic therapy, especially in at-risk patients as described in their report, requires a balanced, evidence-based review, not just of the safety of the medication of interest, but also of the relative toxicities of the recommended therapeutic alternatives, to support an optimal clinical recommendation. Robert D. Colucci, PharmD Daniel B. Carr, MD Curtis Wright IV, MD, MPH Jane L. Loescher, MS Cambridge, Massachusetts 25 July 2006
www.AJConline.org