384
LETTERS TO THE EDITOR
DISCUSSION Memantine has a long elimination half-life of approximately 70 hours, which results in little peak-to-trough concentration variations between doses at steady state (after 2 weeks of therapy).2,6–8 The soon-to-be-discontinued memantine tablets have been given once daily, which can promote medication adherence and appears to be well tolerated.9–12 Newly marketed memantine XR capsules also offer convenient once-daily dosing, but with the unavailability of standard memantine tablets, patients will have no option but to take XR capsules unless the more-expensive oral solution formulation is prescribed. Forest Laboratories has priced memantine XR at a 5% discount to the wholesale acquisition cost of standard tablets,4 but the discontinuation of standard tablets has been viewed as a marketing strategy.13 This analysis suggests that the currently recommended dosing transition may result in a significant increase in steady state peak and trough levels. Based on these pharmacokinetic calculations, practitioners might consider transitioning these patients first to 21 mg XR once daily before escalating to 28 mg. Similarly, this analysis suggests that the recommended dosing transition in individuals with severe renal impairment will also result in significant plasma concentration increases. This analysis was conducted based on population pharmacokinetic parameters, but the data are consistent with the limited data on file from the manufacturer. Pharmacokinetic studies comparing standard tablets with XR formulations are necessary to validate the theoretical construct. Nevertheless, clinicians should monitor patients for adverse drug reactions after the manufacturer-recommended switch from standard tablet to XR because total daily drug dose will be approximately 40% greater. In a 24-week clinical study, memantine XR was well tolerated, with the most common side effects being headache (5.6%) and diarrhea (5.0%).3 Postmarketing surveillance data are awaited to evaluate the side-effect profile with its longterm use. Whether higher drug exposure will enhance drug effects on cognition remains to be seen but will probably never be elucidated in controlled trials because no comparative studies between 10 mg twice daily and 28 mg XR once daily have been performed.2 Sum Lam, PharmD Candace Smith, PharmD Department of Clinical Pharmacy Practice, College of Pharmacy & Health Sciences, St. John’s University, Queens, New York Irving H. Gomolin, MDCM, AGSF Divisions of Geriatric Medicine and Clinical Pharmacology, Winthrop University Hospital, Mineola, New York Department of Medicine, Stony Brook University, Stony Brook, New York
ACKNOWLEDGMENTS Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and
FEBRUARY 2015–VOL. 63, NO. 2
JAGS
has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Lam: literature review, data interpretation, manuscript preparation. Gomolin: concept, data interpretation, manuscript preparation. Smith: pharmacokinetic analysis, data interpretation, manuscript preparation. Sponsor’s Role: No sponsors were involved in the conduct of this study.
REFERENCES 1. Namenda (memantine hydrochloride) prescribing information. Forest Pharmaceuticals, 2013 [on-line]. Available at http://www.frx.com/pi/ namenda_pi.pdf Accessed August 3, 2014. 2. Namenda XR (memantine hydrochloride extended release) prescribing Information. Forest Pharmaceuticals, 2013 [on-line]. Available at http:// www.frx.com/pi/namendaxr_pi.pdf Accessed August 3, 2014. 3. Grossberg GT, Manes F, Allegri RF et al. The safety, tolerability, and efficacy of once-daily memantine (28 mg): A multinational, randomized, double-blind, placebo-controlled trial in patients with moderate-to-severe Alzheimer’s disease taking cholinesterase inhibitors. CNS Drugs 2013; 27:469–478. 4. Healthcare provider communications [on-line]. Available at http://www. fda.gov/downloads/drugs/drugsafety/drugshortages/ucm386064.pdf Accessed August 3, 2014. 5. Forest Laboratories pursues additional market exclusivity to extend Namenda patent [on-line]. Available at http://news.frx.com/press-release/ business-development-news/forest-laboratories-pursues-additional-marketexclusivity-ex Accessed August 3, 2014. 6. Gomolin IH, Smith C, Jeitner TM. Once-daily memantine pharmacokinetic and clinical considerations. J Am Geriatr Soc 2010;58:1812–1813. 7. Periclou A, Ventura D, Rao N et al. Pharmacokinetic study of memantine in healthy and renally impaired subjects. Clin Pharmacol Ther 2006;79:134–143. 8. Liu MY, Sheng-Nan M, Hui-Zhe W et al. Pharmacokinetics of single-dose and multiple-dose memantine in healthy Chinese volunteers using an analytic method of liquid chromatography-tandem mass spectrometry. Clin Ther 2008;30:641–653. 9. Forest Laboratories Clinical Trial Registry. A long-term extension study evaluating the safety and tolerability of four memantine dosing regimens in patients with moderate to severe dementia of the Alzheimer’s type-Phases A and B [on-line]. Available at http://www.forestclinicaltrials.com/ CTRpdf.aspx?pdfId=MEM-MD-03AB Accessed August 20, 2014. 10. Forest Laboratories Clinical Trial Registry. A long-term extension study evaluating the safety and tolerability of BID and QD administration of memantine in patients with mild to moderate dementia of the Alzheimer’s type—Phases A and B [on-line]. Available at http://www.forestclinicaltrials.com/CTRpdf.aspx?pdfId=MEM-MD-11AB Accessed August 20, 2014. 11. Jones RW, Bayer A, Inglis F et al. Safety and tolerability of once-daily versus twice-daily memantine: A randomized, double-blind study in moderate to severe Alzheimer’s disease. Int J Geriatr Psychiatry 2007;22:258–262. 12. Ott BR, Blake LM, Kagan E et al. Open label, multicenter, 28-week extension study of the safety and tolerability of memantine in patients with mild to moderate Alzheimer’s disease. J Neurol 2007;254:351–358. 13. Why is Forest Laboratories discontinuing Namenda? [on-line]. Available at http://www.geripal.org/2014/02/why-is-forest-laboratories-is.html Accessed August 3, 2014.
PRIMARY PERCUTANEOUS CORONARY INTERVENTION FOR ST ELEVATION MYOCARDIAL INFARCTION IN NONAGENARIANS: A MULTICENTER STUDY To the Editor: In the growing population of very old adults, ischemic heart disease remains one of the leading causes of mortality.1,2 Even though primary percutaneous coronary intervention (PCI) has been established as the
JAGS
FEBRUARY 2015–VOL. 63, NO. 2
standard of care, a conservative strategy is often adopted when facing this situation in nonagenarians.3,4 Few studies based on cohorts have suggested the feasibility of invasive management of ST elevation myocardial infarction (STEMI) in nonagenarians.5–8 Data from the largest series of consecutively admitted individuals with STEMI aged 90 and older treated using primary PCI in contemporary practice are presented.
METHODS One hundred forty-five individuals aged 90 and older consecutively hospitalized for STEMI and treated with primary PCI in five international high-volume centers were retrospectively enrolled. Senior interventional cardiologists performed the procedure using a 6-French guiding catheter in all cases once verbal consent for treatment had been obtained from the individual or relatives. The incidence of severe clinical events such as death, recurrent myocardial infarction, target vessel revascularization, stroke, procedure-related complications, acute renal failure (defined as an absolute increase in serum creatinine of ≥0.3 mg/dL or 26.4 lmol/L or a percentage increase in serum creatinine of ≥50% according to the Risk, Injury, Failure, Loss and End-Stage Kidney Disease criteria), and major or clinically relevant bleeding during hospitalization was recorded. Survival data at 6 months and 1 year were collected. Statistical analyses were performed using GraphPad Prism 4 (GraphPad Software, Inc., La Jolla, CA).
LETTERS TO THE EDITOR
385
Table 1. Angiographic Characteristics and Procedural Information Procedural Finding
Value
Hours from symptoms to PCI, mean standard deviation 5.8 7.6 Catheterization access, % Radial 60 Single-vessel coronary disease 53 Single-vessel coronary PCI 74 Infarct-related coronary artery, % Left main 4 Left anterior descending 41 Circumflex 14 Right 45 Coronary artery bypass graft, % 3 Thrombus aspiration, % 14 Thrombolysis in Myocardial Infarction flow grade after procedure, % 0 12 1 1 2 6 3 81 Coronary stenting, % Bare-metal stent 75 Drug-eluting stent 9 Plain old balloon angioplasty 10 Procedure success (%) Successful PCI 87 Failed PCI 11 Complicated PCI 3 Use of protection device (%) 2 Intra-aortic balloon pump, % 0 Use of inotropes during procedure, % 26 PCI = percutaneous coronary intervention.
RESULTS Mean age was 92.5 2.6 (range 90–102), and 62% were female. Associated comorbidities were infrequent; onequarter had a history of coronary heart disease. The initial presentation was Killip Class II to IV in 43%, including cardiogenic shock in 21% and severe pulmonary edema in 10%. Mean left ventricular ejection fraction was 42 13%, and mean creatinine clearance was 49.4 20 mL/ min using the Modification of the Diet in Renal Disease calculator at admission to the coronary care unit after PCI. All participants received a loading dose of 250 to 500 mg of aspirin and 300 to 600 mg of clopidogrel. Glycoprotein IIb/IIIa inhibitors were administered in 36%. Heparin, predominantly unfractionated, was used in 90% of cases. The transradial approach was feasible in 60% but varied between centers from 40% to 84%. The mean time from symptom onset to PCI was 5.8 7.6 hours, but primary PCI was performed within 6 hours after symptom onset in 78% of cases. Multivessel coronary artery disease was present in 47% of participants. Revascularization was limited to the culprit vessel in 74% and multivessel PCI in 26%. A postprocedure final Thrombolysis in Myocardial Infarction flow grade of I was achieved in 1%, of II in 6%, and of III in 81%, with an overall successful procedure rate of 87%. Inotropic support during the procedure was mandatory in 26% of participants (Table 1). The mean hospital length of stay was 5.6 5 days. Clinically relevant bleeding occurred in 4% of participants, acute renal failure in 10%, ventricular arrhythmias in 17%, and one case of stroke during hospital stay. Overall in-
hospital mortality was 24%. There was a positive correlation between in-hospital mortality and Killip class at admission (I, 12.2%; II, 11.8%; III, 26.7%; IV, 47.8%). Overall survival was 58% at 6 months and 49% at 12 months. At 2 years of follow-up, 22% of participants in this series were alive, but 33% of the cohort was lost to follow-up.
DISCUSSION In summary, the developed world is aging, and clinical trials exclude individuals aged 75 and older, especially regarding the use of reperfusion strategies. After myocardial infarction, outcomes in the oldest old adults are poor, and data for individuals aged 90 and older are limited. Similarly to younger individuals in previous large randomized trials, this invasive strategy demonstrated a high rate of achieved reperfusion of the infarct-related artery and a low incidence of procedure-related complications in this population. Use of radial access and contemporary antithrombotic treatments in the series was associated with lower mortality than expected considering the severe clinical presentation. Nonetheless, short- and long-term mortality remain high in this age group. This study suggests that primary PCI can be performed using a transradial approach with reasonable safety, satisfactory angiographic results, and a low incidence of procedure-related complications in selected nonagenarians with STEMI. Experienced operators may routinely choose the transradial approach to reduce
386
LETTERS TO THE EDITOR
adverse events, particularly puncture site–related bleeding complications. Thibaut Petroni, MD Cardiology Institute, H^ opital Pitie-Salp^etriere, Assistance Publique – H^ opitaux de Paris, Universite Pierre-et-MarieCurie, Paris, France Azfar Zaman, MD Department of Cardiology, Freeman Hospital and Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
FEBRUARY 2015–VOL. 63, NO. 2
3.
4.
5.
6.
Jean-Louis Georges, MD Cardiology Department, H^ opital Andre Mignot, Versailles, France Nadjib Hammoudi, MD Emmanuel Berman, BSc Cardiology Institute, H^ opital Pitie-Salp^etriere, Assistance Publique – H^ opitaux de Paris, Universite Pierre-et-MarieCurie, Paris, France Amit Segev, MD Chaim Sheba Medical Center, Heart Institute, TelHashomer, Israel Jean-Michel Juliard, MD Cardiology Department, H^ opital Bichat, Assistance Publique – H^ opitaux de Paris, Paris, France Olivier Barthelemy, MD Johanne Silvain, MD, PhD Remi Choussat, MD Claude Le Feuvre, MD, PhD Gerard Helft, MD, PhD Cardiology Institute, H^ opital Pitie-Salp^etriere, Assistance Publique – H^ opitaux de Paris, Universite Pierre-et-MarieCurie, Paris, France
7.
8.
JAGS
National Center for Health Statistics, 2006 [on-line]. Available at http:// www.ncbi.nlm.nih.gov/books/NBK21002/ Accessed January 2014. Alexander KP, Newby LK, Armstrong PW et al. Acute coronary care in the elderly, part II: ST-segment-elevation myocardial infarction: A scientific statement for healthcare professionals from the American Heart Association Council on Clinical Cardiology: In collaboration with the Society of Geriatric Cardiology. Circulation 2007;115:2570–2589. Task force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC), Steg PG, James SK et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012;33:2569– 2619. Danzi GB, Centola M, Pomidossi GA et al. Usefulness of primary angioplasty in nonagenarians with acute myocardial infarction. Am J Cardiol 2010;106:770–773. Ionescu CN, Amuchastegui M, Ionescu S et al. Treatment and outcomes of nonagenarians with ST-elevation myocardial infarction. J Invasive Cardiol 2010;22:474–478. Salinas P, Galeote G, Martin-Reyes R et al. Primary percutaneous coronary intervention for ST-segment elevation acute myocardial infarction in nonagenarian patients: Results from a Spanish multicentre registry. EuroIntervention 2011;6:1080–1084. Rigattieri S, Cera M, Sciahbasi A et al. Primary percutaneous coronary intervention in nonagenarians: Six-month outcomes from a single-center registry. J Invasive Cardiol 2013;25:242–245.
EXERCISE WITHOUT DIGESTIVE ENZYME SUPPLEMENTATION WORSENS NUTRITIONAL STATUS OF FRAIL OLDER WOMEN To the Editor: Previous studies have examined whether use of a nutritional supplement increases the effect of an exercise intervention in frail older people.1 The possibility of impaired nutritional status in response to exercise without nutritional intervention is proposed because increasing physical activity and stimulating muscle synthesis will increase nutritional demand. Although there is no clear evidence of changes in protein use in aging,2 improvement of nutritional status with digestive enzyme supplementation was reported.3,4 The effects of an 8-week exercise intervention with digestive enzyme supplementation on nutritional status and physical function was examined.
ACKNOWLEDGMENTS
METHODS
Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Dr. Petroni was funded by the French Federation of Cardiology fellowship grant. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Author Contributions: All authors contributed to this paper. Sponsor’s Role: The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Participants were frail older women who could conduct the proposed exercise program. Subjects were excluded if they had experienced a heart attack or stroke within the previous 6 months or had a condition that exercise might worsen. Fifty-two women applied from three nursing homes. Random allocation to groups was not possible because of the existing high workload of nursing home staff. One of three groups was therefore assigned to each nursing home; exercise, exercise with supplementation, and control. One participant who died during the study was excluded from the analysis. The exercise intervention was a 90-minute program twice weekly with one occupational therapist and one nurse. The program included gymnastics, balloon volleyball, bowling, and dance. Supplementation was 1 g of Berizym (Shionogi & Co., Ltd., Chuo-ku, Osaka, Japan) three times daily. One gram of Berizym includes concentrated pancreatic digestive enzyme (312.5 mg), an Aspergillus digestive enzyme (75 mg), bacterial lipolysis enzyme (62.5 mg), and fibrin catabolic enzyme (37.5 mg).
REFERENCES 1. Mehta RH, Granger CB, Alexander KP et al. Reperfusion strategies for acute myocardial infarction in the elderly: Benefits and risks. J Am Coll Cardiol 2005;45:471–478. 2. National Center for Health Statistics. Health, United States, 2006: With Chartbook on Trends in the Health of Americans. Hyattsville, MD:
Copyright of Journal of the American Geriatrics Society is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
LETTERS TO THE EDITOR
DISCUSSION Memantine has a long elimination half-life of approximately 70 hours, which results in little peak-to-trough concentration variations between doses at steady state (after 2 weeks of therapy).2,6–8 The soon-to-be-discontinued memantine tablets have been given once daily, which can promote medication adherence and appears to be well tolerated.9–12 Newly marketed memantine XR capsules also offer convenient once-daily dosing, but with the unavailability of standard memantine tablets, patients will have no option but to take XR capsules unless the more-expensive oral solution formulation is prescribed. Forest Laboratories has priced memantine XR at a 5% discount to the wholesale acquisition cost of standard tablets,4 but the discontinuation of standard tablets has been viewed as a marketing strategy.13 This analysis suggests that the currently recommended dosing transition may result in a significant increase in steady state peak and trough levels. Based on these pharmacokinetic calculations, practitioners might consider transitioning these patients first to 21 mg XR once daily before escalating to 28 mg. Similarly, this analysis suggests that the recommended dosing transition in individuals with severe renal impairment will also result in significant plasma concentration increases. This analysis was conducted based on population pharmacokinetic parameters, but the data are consistent with the limited data on file from the manufacturer. Pharmacokinetic studies comparing standard tablets with XR formulations are necessary to validate the theoretical construct. Nevertheless, clinicians should monitor patients for adverse drug reactions after the manufacturer-recommended switch from standard tablet to XR because total daily drug dose will be approximately 40% greater. In a 24-week clinical study, memantine XR was well tolerated, with the most common side effects being headache (5.6%) and diarrhea (5.0%).3 Postmarketing surveillance data are awaited to evaluate the side-effect profile with its longterm use. Whether higher drug exposure will enhance drug effects on cognition remains to be seen but will probably never be elucidated in controlled trials because no comparative studies between 10 mg twice daily and 28 mg XR once daily have been performed.2 Sum Lam, PharmD Candace Smith, PharmD Department of Clinical Pharmacy Practice, College of Pharmacy & Health Sciences, St. John’s University, Queens, New York Irving H. Gomolin, MDCM, AGSF Divisions of Geriatric Medicine and Clinical Pharmacology, Winthrop University Hospital, Mineola, New York Department of Medicine, Stony Brook University, Stony Brook, New York
ACKNOWLEDGMENTS Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and
FEBRUARY 2015–VOL. 63, NO. 2
JAGS
has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Lam: literature review, data interpretation, manuscript preparation. Gomolin: concept, data interpretation, manuscript preparation. Smith: pharmacokinetic analysis, data interpretation, manuscript preparation. Sponsor’s Role: No sponsors were involved in the conduct of this study.
REFERENCES 1. Namenda (memantine hydrochloride) prescribing information. Forest Pharmaceuticals, 2013 [on-line]. Available at http://www.frx.com/pi/ namenda_pi.pdf Accessed August 3, 2014. 2. Namenda XR (memantine hydrochloride extended release) prescribing Information. Forest Pharmaceuticals, 2013 [on-line]. Available at http:// www.frx.com/pi/namendaxr_pi.pdf Accessed August 3, 2014. 3. Grossberg GT, Manes F, Allegri RF et al. The safety, tolerability, and efficacy of once-daily memantine (28 mg): A multinational, randomized, double-blind, placebo-controlled trial in patients with moderate-to-severe Alzheimer’s disease taking cholinesterase inhibitors. CNS Drugs 2013; 27:469–478. 4. Healthcare provider communications [on-line]. Available at http://www. fda.gov/downloads/drugs/drugsafety/drugshortages/ucm386064.pdf Accessed August 3, 2014. 5. Forest Laboratories pursues additional market exclusivity to extend Namenda patent [on-line]. Available at http://news.frx.com/press-release/ business-development-news/forest-laboratories-pursues-additional-marketexclusivity-ex Accessed August 3, 2014. 6. Gomolin IH, Smith C, Jeitner TM. Once-daily memantine pharmacokinetic and clinical considerations. J Am Geriatr Soc 2010;58:1812–1813. 7. Periclou A, Ventura D, Rao N et al. Pharmacokinetic study of memantine in healthy and renally impaired subjects. Clin Pharmacol Ther 2006;79:134–143. 8. Liu MY, Sheng-Nan M, Hui-Zhe W et al. Pharmacokinetics of single-dose and multiple-dose memantine in healthy Chinese volunteers using an analytic method of liquid chromatography-tandem mass spectrometry. Clin Ther 2008;30:641–653. 9. Forest Laboratories Clinical Trial Registry. A long-term extension study evaluating the safety and tolerability of four memantine dosing regimens in patients with moderate to severe dementia of the Alzheimer’s type-Phases A and B [on-line]. Available at http://www.forestclinicaltrials.com/ CTRpdf.aspx?pdfId=MEM-MD-03AB Accessed August 20, 2014. 10. Forest Laboratories Clinical Trial Registry. A long-term extension study evaluating the safety and tolerability of BID and QD administration of memantine in patients with mild to moderate dementia of the Alzheimer’s type—Phases A and B [on-line]. Available at http://www.forestclinicaltrials.com/CTRpdf.aspx?pdfId=MEM-MD-11AB Accessed August 20, 2014. 11. Jones RW, Bayer A, Inglis F et al. Safety and tolerability of once-daily versus twice-daily memantine: A randomized, double-blind study in moderate to severe Alzheimer’s disease. Int J Geriatr Psychiatry 2007;22:258–262. 12. Ott BR, Blake LM, Kagan E et al. Open label, multicenter, 28-week extension study of the safety and tolerability of memantine in patients with mild to moderate Alzheimer’s disease. J Neurol 2007;254:351–358. 13. Why is Forest Laboratories discontinuing Namenda? [on-line]. Available at http://www.geripal.org/2014/02/why-is-forest-laboratories-is.html Accessed August 3, 2014.
PRIMARY PERCUTANEOUS CORONARY INTERVENTION FOR ST ELEVATION MYOCARDIAL INFARCTION IN NONAGENARIANS: A MULTICENTER STUDY To the Editor: In the growing population of very old adults, ischemic heart disease remains one of the leading causes of mortality.1,2 Even though primary percutaneous coronary intervention (PCI) has been established as the
JAGS
FEBRUARY 2015–VOL. 63, NO. 2
standard of care, a conservative strategy is often adopted when facing this situation in nonagenarians.3,4 Few studies based on cohorts have suggested the feasibility of invasive management of ST elevation myocardial infarction (STEMI) in nonagenarians.5–8 Data from the largest series of consecutively admitted individuals with STEMI aged 90 and older treated using primary PCI in contemporary practice are presented.
METHODS One hundred forty-five individuals aged 90 and older consecutively hospitalized for STEMI and treated with primary PCI in five international high-volume centers were retrospectively enrolled. Senior interventional cardiologists performed the procedure using a 6-French guiding catheter in all cases once verbal consent for treatment had been obtained from the individual or relatives. The incidence of severe clinical events such as death, recurrent myocardial infarction, target vessel revascularization, stroke, procedure-related complications, acute renal failure (defined as an absolute increase in serum creatinine of ≥0.3 mg/dL or 26.4 lmol/L or a percentage increase in serum creatinine of ≥50% according to the Risk, Injury, Failure, Loss and End-Stage Kidney Disease criteria), and major or clinically relevant bleeding during hospitalization was recorded. Survival data at 6 months and 1 year were collected. Statistical analyses were performed using GraphPad Prism 4 (GraphPad Software, Inc., La Jolla, CA).
LETTERS TO THE EDITOR
385
Table 1. Angiographic Characteristics and Procedural Information Procedural Finding
Value
Hours from symptoms to PCI, mean standard deviation 5.8 7.6 Catheterization access, % Radial 60 Single-vessel coronary disease 53 Single-vessel coronary PCI 74 Infarct-related coronary artery, % Left main 4 Left anterior descending 41 Circumflex 14 Right 45 Coronary artery bypass graft, % 3 Thrombus aspiration, % 14 Thrombolysis in Myocardial Infarction flow grade after procedure, % 0 12 1 1 2 6 3 81 Coronary stenting, % Bare-metal stent 75 Drug-eluting stent 9 Plain old balloon angioplasty 10 Procedure success (%) Successful PCI 87 Failed PCI 11 Complicated PCI 3 Use of protection device (%) 2 Intra-aortic balloon pump, % 0 Use of inotropes during procedure, % 26 PCI = percutaneous coronary intervention.
RESULTS Mean age was 92.5 2.6 (range 90–102), and 62% were female. Associated comorbidities were infrequent; onequarter had a history of coronary heart disease. The initial presentation was Killip Class II to IV in 43%, including cardiogenic shock in 21% and severe pulmonary edema in 10%. Mean left ventricular ejection fraction was 42 13%, and mean creatinine clearance was 49.4 20 mL/ min using the Modification of the Diet in Renal Disease calculator at admission to the coronary care unit after PCI. All participants received a loading dose of 250 to 500 mg of aspirin and 300 to 600 mg of clopidogrel. Glycoprotein IIb/IIIa inhibitors were administered in 36%. Heparin, predominantly unfractionated, was used in 90% of cases. The transradial approach was feasible in 60% but varied between centers from 40% to 84%. The mean time from symptom onset to PCI was 5.8 7.6 hours, but primary PCI was performed within 6 hours after symptom onset in 78% of cases. Multivessel coronary artery disease was present in 47% of participants. Revascularization was limited to the culprit vessel in 74% and multivessel PCI in 26%. A postprocedure final Thrombolysis in Myocardial Infarction flow grade of I was achieved in 1%, of II in 6%, and of III in 81%, with an overall successful procedure rate of 87%. Inotropic support during the procedure was mandatory in 26% of participants (Table 1). The mean hospital length of stay was 5.6 5 days. Clinically relevant bleeding occurred in 4% of participants, acute renal failure in 10%, ventricular arrhythmias in 17%, and one case of stroke during hospital stay. Overall in-
hospital mortality was 24%. There was a positive correlation between in-hospital mortality and Killip class at admission (I, 12.2%; II, 11.8%; III, 26.7%; IV, 47.8%). Overall survival was 58% at 6 months and 49% at 12 months. At 2 years of follow-up, 22% of participants in this series were alive, but 33% of the cohort was lost to follow-up.
DISCUSSION In summary, the developed world is aging, and clinical trials exclude individuals aged 75 and older, especially regarding the use of reperfusion strategies. After myocardial infarction, outcomes in the oldest old adults are poor, and data for individuals aged 90 and older are limited. Similarly to younger individuals in previous large randomized trials, this invasive strategy demonstrated a high rate of achieved reperfusion of the infarct-related artery and a low incidence of procedure-related complications in this population. Use of radial access and contemporary antithrombotic treatments in the series was associated with lower mortality than expected considering the severe clinical presentation. Nonetheless, short- and long-term mortality remain high in this age group. This study suggests that primary PCI can be performed using a transradial approach with reasonable safety, satisfactory angiographic results, and a low incidence of procedure-related complications in selected nonagenarians with STEMI. Experienced operators may routinely choose the transradial approach to reduce
386
LETTERS TO THE EDITOR
adverse events, particularly puncture site–related bleeding complications. Thibaut Petroni, MD Cardiology Institute, H^ opital Pitie-Salp^etriere, Assistance Publique – H^ opitaux de Paris, Universite Pierre-et-MarieCurie, Paris, France Azfar Zaman, MD Department of Cardiology, Freeman Hospital and Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
FEBRUARY 2015–VOL. 63, NO. 2
3.
4.
5.
6.
Jean-Louis Georges, MD Cardiology Department, H^ opital Andre Mignot, Versailles, France Nadjib Hammoudi, MD Emmanuel Berman, BSc Cardiology Institute, H^ opital Pitie-Salp^etriere, Assistance Publique – H^ opitaux de Paris, Universite Pierre-et-MarieCurie, Paris, France Amit Segev, MD Chaim Sheba Medical Center, Heart Institute, TelHashomer, Israel Jean-Michel Juliard, MD Cardiology Department, H^ opital Bichat, Assistance Publique – H^ opitaux de Paris, Paris, France Olivier Barthelemy, MD Johanne Silvain, MD, PhD Remi Choussat, MD Claude Le Feuvre, MD, PhD Gerard Helft, MD, PhD Cardiology Institute, H^ opital Pitie-Salp^etriere, Assistance Publique – H^ opitaux de Paris, Universite Pierre-et-MarieCurie, Paris, France
7.
8.
JAGS
National Center for Health Statistics, 2006 [on-line]. Available at http:// www.ncbi.nlm.nih.gov/books/NBK21002/ Accessed January 2014. Alexander KP, Newby LK, Armstrong PW et al. Acute coronary care in the elderly, part II: ST-segment-elevation myocardial infarction: A scientific statement for healthcare professionals from the American Heart Association Council on Clinical Cardiology: In collaboration with the Society of Geriatric Cardiology. Circulation 2007;115:2570–2589. Task force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC), Steg PG, James SK et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012;33:2569– 2619. Danzi GB, Centola M, Pomidossi GA et al. Usefulness of primary angioplasty in nonagenarians with acute myocardial infarction. Am J Cardiol 2010;106:770–773. Ionescu CN, Amuchastegui M, Ionescu S et al. Treatment and outcomes of nonagenarians with ST-elevation myocardial infarction. J Invasive Cardiol 2010;22:474–478. Salinas P, Galeote G, Martin-Reyes R et al. Primary percutaneous coronary intervention for ST-segment elevation acute myocardial infarction in nonagenarian patients: Results from a Spanish multicentre registry. EuroIntervention 2011;6:1080–1084. Rigattieri S, Cera M, Sciahbasi A et al. Primary percutaneous coronary intervention in nonagenarians: Six-month outcomes from a single-center registry. J Invasive Cardiol 2013;25:242–245.
EXERCISE WITHOUT DIGESTIVE ENZYME SUPPLEMENTATION WORSENS NUTRITIONAL STATUS OF FRAIL OLDER WOMEN To the Editor: Previous studies have examined whether use of a nutritional supplement increases the effect of an exercise intervention in frail older people.1 The possibility of impaired nutritional status in response to exercise without nutritional intervention is proposed because increasing physical activity and stimulating muscle synthesis will increase nutritional demand. Although there is no clear evidence of changes in protein use in aging,2 improvement of nutritional status with digestive enzyme supplementation was reported.3,4 The effects of an 8-week exercise intervention with digestive enzyme supplementation on nutritional status and physical function was examined.
ACKNOWLEDGMENTS
METHODS
Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Dr. Petroni was funded by the French Federation of Cardiology fellowship grant. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Author Contributions: All authors contributed to this paper. Sponsor’s Role: The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Participants were frail older women who could conduct the proposed exercise program. Subjects were excluded if they had experienced a heart attack or stroke within the previous 6 months or had a condition that exercise might worsen. Fifty-two women applied from three nursing homes. Random allocation to groups was not possible because of the existing high workload of nursing home staff. One of three groups was therefore assigned to each nursing home; exercise, exercise with supplementation, and control. One participant who died during the study was excluded from the analysis. The exercise intervention was a 90-minute program twice weekly with one occupational therapist and one nurse. The program included gymnastics, balloon volleyball, bowling, and dance. Supplementation was 1 g of Berizym (Shionogi & Co., Ltd., Chuo-ku, Osaka, Japan) three times daily. One gram of Berizym includes concentrated pancreatic digestive enzyme (312.5 mg), an Aspergillus digestive enzyme (75 mg), bacterial lipolysis enzyme (62.5 mg), and fibrin catabolic enzyme (37.5 mg).
REFERENCES 1. Mehta RH, Granger CB, Alexander KP et al. Reperfusion strategies for acute myocardial infarction in the elderly: Benefits and risks. J Am Coll Cardiol 2005;45:471–478. 2. National Center for Health Statistics. Health, United States, 2006: With Chartbook on Trends in the Health of Americans. Hyattsville, MD:
Copyright of Journal of the American Geriatrics Society is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
