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The need to improve cardiac care after acute coronary syndrome
Hellenic Journal of Cardiology 60 (2019) 254e255
Contents lists available at ScienceDirect
Hellenic Journal of Cardiology journal homepage: http://www.journals.elsevier.com/ hellenic-journal-of-cardiology/
Editor's Page
The need to improve cardiac care after acute coronary syndrome a b s t r a c t Keywords: Acute coronary syndrome Low density lipoprotein cholesterol Statins Adherence
Patients who experience acute coronary syndrome (ACS) are at increased risk of new cardiovascular (CV) events. The main strategies for prevention of recurrence of CV events is the protection from ruptured plaque, thrombus formation, occlusion or downstream embolization in the coronary artery. The percutaneous coronary intervention (PCI) with stenting and anticoagulants, 3-hydroxy-3-methyl-glutarylcoenzyme A reductase inhibitors (HMGCoAi, commonly called statins) and neurohormonal inhibition, has led to a notable decrease in 1-year mortality events. Today it is well documented that all patients with an ACS should be treated early, intensively and continuously for lowering the LDL-C values to the recommended goals. Regularly interviewing by trained health care personnel and post-discharge followup of patients after ACS seems to be more effective concerning adherence to statin for achieving LDL-C treatment goals compared with the standard of care. © 2019 Hellenic Society of Cardiology. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Patients who experience acute coronary syndrome (ACS) are at increased risk of new cardiovascular (CV) events. The main strategies for prevention of recurrence of CV events is the protection from ruptured plaque, thrombus formation, occlusion or downstream embolization in the coronary artery. The percutaneous coronary intervention (PCI) with stenting and anticoagulants, 3hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (HMGCoAi, commonly called statins) and neurohormonal inhibition, has led to a notable decrease in 1-year mortality from approximately 22% in 1995 to approximately 11% by 2014.1 The FAST-MI (French Registry on Acute ST-elevation and non-ST-elevation Myocardial Infarction) and longitudinal Swedish (SWEDEHEART) program, examined the long-term outcomes of myocardial infarction (MI) prognosis from 1995 to 2014 [1.] and have shown that STEMI (ST-segment elevation myocardial infarction) and NSTEMI (non-ST-segment elevation myocardial infarction) patients mortality has dropped to nearly half. However, the CV events rates are still high1,2 as was shown by long-term outcomes studies. For example, in REACH registry (International Reduction of Atherothrombosis for Continued Health, included 37,154 patients with established atherothrombotic disease), among patients with coronary artery disease (CAD), CV death, MI or stroke occurred after 1-year followup in 4.5% of patients.3 Of note, that the adherence rates with all evidence-based medications at baseline and at 1 year were 46.7% and 48.2%, respectively. Furthermore, the nonadherence with any medication at baseline and at 1 year after ACS were significantly correlated with an increased risk of CV events. Data from randomized clinical trials (RCT) have provided convincing evidence for the benefit of aggressive management of ACS. Moreover, RCTs and meta-analyses reveal that early and rigorous lipid lowering therapy Peer review under responsibility of Hellenic Society of Cardiology.
is associated with fewer CV events. In the IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial, included 18,144 patients with ACS), ezetimibe was added to simvastatin 40 mg4 or placebo. A fewer events (32.7 vs. 34.7%) were recorded in the group taking simvastatin plus ezetimibe. The average plasma LDL-C values during the study was 70 mg/dL (1.8 mmol/L) in the simvastatin group and 55 mg/dL (1.4 mmol/L) in ezetimibe plus simvastatin group. Also, ischemic stroke was reduced by 21% in this trial. In the FOURIER trial, in the subgroup of patients with a history of MI (81% of 27,564 patients) followed up for 2.2 years, the addition of human monoclonal antibody proprotein convertase subtilisin-kexin type 9 (PCSK9i, evolocumab) to high intensity statin therapy (69% of patients) resulted in a 15% relative risk reduction (RRR) of the composite primary endpoint.5 Furthermore, patients who achieved the lowest LDL-C values also had the lowest risk of CV events.5 Similarly, in the ODYSSEY (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) Outcomes trial, which included 18,924 patients with ACS and were followed up for 2.8 years, alirocumab added to high intensity statin therapy (89% of patients) resulted in a 15% RRR in the composite endpoint. Of note that treatment with alirocumab was associated with a 15% relative reduction in all-cause mortality.6 All above, intensely support that continuous implementation of evidence-based treatment strategies considerably reduces CV complications and increases survival of patients with ACS, and thereby contributes to an improved life-expectancy in the whole population. Therefore, today it is well documented that all patients with an ACS should be treated early, intensively and continuously for lowering the LDL-C values to the recommended goals.7 Thus, the adherence to lipid management in those patients should be supported by “physician-led motivational intervention”. In the current
https://doi.org/10.1016/j.hjc.2019.12.002 1109-9666/© 2019 Hellenic Society of Cardiology. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).
Editor's Page / Hellenic Journal of Cardiology 60 (2019) 254e255
issue of Hellenic Journal of Cardiology, Boulmpou et al8 aimed to examine the effect of a patient-centered, physician-led motivational intervention following ACS. Authors believe, that regularly interviewing by trained health care personnel and post-discharge follow-up will be more effective concerning adherence to statin for achieving LDL-C treatment goals compared with the standard of care, over a 12-month period. This was documented in NAILED-ACS (Nurse-based Age-independent Intervention to Limit Evolution of Disease after Acute Coronary Syndrome) trial. The trial comprises two groups, one with nurse-led annual follow-up and medical titration by telephone to reach set intervention targets and one with usual care. The rate of adherence to statin treatment was almost 90% after a mean follow-up time of 3.8 years in a community-based ACS population with a nurse-led telephonebased intervention and 85% in the usual care control group.9 In the substudy of IDEAL-LDL (Motivational interviewing to support low-density lipoprotein cholesterol (LDL-C) therapeutic goals and lipid-lowering therapy compliance in patients with acute coronary syndromes), which included 357 ACS patients, was reported that the combination of statin, dual antiplatelet therapy and betablockers were prescribed to 79.6% of patients upon discharge.10 A renin-angiotensin-aldosterone system inhibitor and a betablocker were prescribed to 67.3 and 91.8% of patients with LVEF 40%, respectively. From CAD patients only 22.3% had recommended LDL-C values of <70 mg/dl at admission. Among ACS patients who were already under high intensity statins before hospitalisation and without reaching the recommended LDL-C values, only 13.3% received additional therapy with ezetimibe at discharge.10 Adherence to statins varies between studies. The rates of adherence are usually better in RCT than observational studies/realworld settings. In Lemestra et al meta-analysis was found the statin adherence rates of 49% in observational studies and 90.3% in controlled trials.11 In the EUROASPIRE IV study of a crosssectional European ACS cohort, 85.7% were on lipid lowering medication >6 months after the event.12 Individual reasons for nonadherence concerning statin treatment after ACS have been inadequately investigated. In meta analyses of adherence, female gender, low education, high-dose treatment, polypharmacy and poor prescriber-patient relationships have been highlighted. Gencer et al13 found that the doctor's decision to stop treatment was the most prevalent reason for treatment discontinuation, followed by side effects. In the USAGE (Understanding Statin Use in America and Gaps in Patient Education) study, side effects were the primary reason for treatment discontinuation.14 Reported side effects of the statin group are mainly muscle symptoms in 7e29% of patients, but also included rhabdomyolysis, memory impairment, cataracts, renal dysfunction and diabetes. Although, placebo-controlled trials have not been able to show increased levels of side effects. 1. Conclusions Long-term follow-up of patients with ACS either by telephonebased interventions or motivational interviewing, may result in higher adherence to medical treatment compared with usual care. A certain number of unsubstantiated discontinuations seems unavoidable, but the proportion of avoidable causes for discontinuation may be reduced with duration of follow-up. Thus, the strengthening lipid lowering medication by healthcare personnel (doctors, nurses and others) on the implication of the evidencebased guidelines should be enhanced. Therefore, adherence efficacy trials and may fill the gap regarding how adherence interventions should be implemented into clinical care.
255
Declaration of conflicting interests The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Funding The author received no financial support for the research, authorship, and/or publication of this article.
References 1. Szummer K, Jernberg T, Wallentin L, et al. From Early Pharmacology to Recent Pharmacology Interventions in Acute Coronary Syndromes: JACC State-of-theArt Review. J Am Coll Cardiol. 2019;74:1618e1636. 2. Puymirat E, Simon T, Cayla G, et al. Acute myocardial infarction: changes in patient characteristics, management, and 6-month outcomes over a period of 20 years in the FAST-MI Program (French Registry of Acute ST-Elevation or NonST-Elevation Myocardial Infarction) 1995 to 2015. Circulation. 2017;136: 1908e1919. 3. Kumbhani DJ, Steg PG, Cannon CP, et al. Adherence to secondary prevention medications and four-year outcomes in outpatients with atherosclerosis. Am J Med. 2013;126:693e700. 4. Cannon CP, Blazing MA, Giugliano RP, et al, IMPROVE-IT Investigators. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387e2397. 5. Giugliano RP, Pedersen TR, Park JG, et al. FOURIER Investigators. Clinical efficacy and safety of achieving very low LDL- cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial. Lancet. 2017;390:1962e1971. 6. Schwartz GG, Steg PG, Szarek M, et al. ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379:2097e2107. 7. Mach C, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. pii: ehz455 Eur Heart J. 2019. https://doi.org/10.1093/eurheartj/ehz455 [Epub ahead of print]. 8. Boulmpou A, Kartas A, Farmakis I, et al. Motivational interviewing to support LDL-C therapeutic goals and lipid-lowering therapy compliance in patients with acute coronary syndromes (IDEAL-LDL) study: rationale and design. Hellenic J Cardiol. 2019;60:249e253. 9. Daniel H, Christian W, Robin H, Lars S, Thomas M. Statin treatment after acute coronary syndrome: Adherence and reasons for non-adherence in a randomized controlled intervention trial. Sci Rep. 2019;9:12079. 10. Farmakis I, Zafeiropoulos S, Kartas A, et al. Treatment practices and lipid profile of patients with acute coronary syndrome: results from a tertiary care hospital. Acta Cardiol. 2019 Jun 20:1e8. 11. Lemstra M, Blackburn D, Crawley A, Fung R. Proportion and risk indicators of nonadherence to statin therapy: a meta-analysis. Can J Cardiol. 2012;28: 574e580. 12. Kotseva K, Wood D, De Bacquer D, et al. EUROASPIRE IV. A European Society of Cardiology survey on the lifestyle, risk factor and therapeutic management of coronary patients from 24 European countries. Eur J Prev Cardiol. 2016;23: 636e648. 13. Gencer B, Rodondi N, Auer R, et al. Reasons for discontinuation of recommended therapies according to the patients after acute coronary syndromes. Eur J Intern Med. 2015;26:56e62. 14. Cohen JD, Brinton EA, Ito MK, Jacobson TA. Understanding Statin Use in America and Gaps in Patient Education (USAGE): an internet-based survey of 10,138 current and former statin users. J Clin Lipidol. 2012;6:208e215.
Genovefa Kolovou* Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece *
Corresponding author. Genovefa Kolovou, Onassis Cardiac Surgery Center, 356 Sygrou Ave, 176 74 Athens, Greece. Tel: þ30 210 9493520, Fax: þ30 210 9493336. E-mail address: [email protected]. 10 October 2019
Contents lists available at ScienceDirect
Hellenic Journal of Cardiology journal homepage: http://www.journals.elsevier.com/ hellenic-journal-of-cardiology/
Editor's Page
The need to improve cardiac care after acute coronary syndrome a b s t r a c t Keywords: Acute coronary syndrome Low density lipoprotein cholesterol Statins Adherence
Patients who experience acute coronary syndrome (ACS) are at increased risk of new cardiovascular (CV) events. The main strategies for prevention of recurrence of CV events is the protection from ruptured plaque, thrombus formation, occlusion or downstream embolization in the coronary artery. The percutaneous coronary intervention (PCI) with stenting and anticoagulants, 3-hydroxy-3-methyl-glutarylcoenzyme A reductase inhibitors (HMGCoAi, commonly called statins) and neurohormonal inhibition, has led to a notable decrease in 1-year mortality events. Today it is well documented that all patients with an ACS should be treated early, intensively and continuously for lowering the LDL-C values to the recommended goals. Regularly interviewing by trained health care personnel and post-discharge followup of patients after ACS seems to be more effective concerning adherence to statin for achieving LDL-C treatment goals compared with the standard of care. © 2019 Hellenic Society of Cardiology. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Patients who experience acute coronary syndrome (ACS) are at increased risk of new cardiovascular (CV) events. The main strategies for prevention of recurrence of CV events is the protection from ruptured plaque, thrombus formation, occlusion or downstream embolization in the coronary artery. The percutaneous coronary intervention (PCI) with stenting and anticoagulants, 3hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (HMGCoAi, commonly called statins) and neurohormonal inhibition, has led to a notable decrease in 1-year mortality from approximately 22% in 1995 to approximately 11% by 2014.1 The FAST-MI (French Registry on Acute ST-elevation and non-ST-elevation Myocardial Infarction) and longitudinal Swedish (SWEDEHEART) program, examined the long-term outcomes of myocardial infarction (MI) prognosis from 1995 to 2014 [1.] and have shown that STEMI (ST-segment elevation myocardial infarction) and NSTEMI (non-ST-segment elevation myocardial infarction) patients mortality has dropped to nearly half. However, the CV events rates are still high1,2 as was shown by long-term outcomes studies. For example, in REACH registry (International Reduction of Atherothrombosis for Continued Health, included 37,154 patients with established atherothrombotic disease), among patients with coronary artery disease (CAD), CV death, MI or stroke occurred after 1-year followup in 4.5% of patients.3 Of note, that the adherence rates with all evidence-based medications at baseline and at 1 year were 46.7% and 48.2%, respectively. Furthermore, the nonadherence with any medication at baseline and at 1 year after ACS were significantly correlated with an increased risk of CV events. Data from randomized clinical trials (RCT) have provided convincing evidence for the benefit of aggressive management of ACS. Moreover, RCTs and meta-analyses reveal that early and rigorous lipid lowering therapy Peer review under responsibility of Hellenic Society of Cardiology.
is associated with fewer CV events. In the IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial, included 18,144 patients with ACS), ezetimibe was added to simvastatin 40 mg4 or placebo. A fewer events (32.7 vs. 34.7%) were recorded in the group taking simvastatin plus ezetimibe. The average plasma LDL-C values during the study was 70 mg/dL (1.8 mmol/L) in the simvastatin group and 55 mg/dL (1.4 mmol/L) in ezetimibe plus simvastatin group. Also, ischemic stroke was reduced by 21% in this trial. In the FOURIER trial, in the subgroup of patients with a history of MI (81% of 27,564 patients) followed up for 2.2 years, the addition of human monoclonal antibody proprotein convertase subtilisin-kexin type 9 (PCSK9i, evolocumab) to high intensity statin therapy (69% of patients) resulted in a 15% relative risk reduction (RRR) of the composite primary endpoint.5 Furthermore, patients who achieved the lowest LDL-C values also had the lowest risk of CV events.5 Similarly, in the ODYSSEY (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) Outcomes trial, which included 18,924 patients with ACS and were followed up for 2.8 years, alirocumab added to high intensity statin therapy (89% of patients) resulted in a 15% RRR in the composite endpoint. Of note that treatment with alirocumab was associated with a 15% relative reduction in all-cause mortality.6 All above, intensely support that continuous implementation of evidence-based treatment strategies considerably reduces CV complications and increases survival of patients with ACS, and thereby contributes to an improved life-expectancy in the whole population. Therefore, today it is well documented that all patients with an ACS should be treated early, intensively and continuously for lowering the LDL-C values to the recommended goals.7 Thus, the adherence to lipid management in those patients should be supported by “physician-led motivational intervention”. In the current
https://doi.org/10.1016/j.hjc.2019.12.002 1109-9666/© 2019 Hellenic Society of Cardiology. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).
Editor's Page / Hellenic Journal of Cardiology 60 (2019) 254e255
issue of Hellenic Journal of Cardiology, Boulmpou et al8 aimed to examine the effect of a patient-centered, physician-led motivational intervention following ACS. Authors believe, that regularly interviewing by trained health care personnel and post-discharge follow-up will be more effective concerning adherence to statin for achieving LDL-C treatment goals compared with the standard of care, over a 12-month period. This was documented in NAILED-ACS (Nurse-based Age-independent Intervention to Limit Evolution of Disease after Acute Coronary Syndrome) trial. The trial comprises two groups, one with nurse-led annual follow-up and medical titration by telephone to reach set intervention targets and one with usual care. The rate of adherence to statin treatment was almost 90% after a mean follow-up time of 3.8 years in a community-based ACS population with a nurse-led telephonebased intervention and 85% in the usual care control group.9 In the substudy of IDEAL-LDL (Motivational interviewing to support low-density lipoprotein cholesterol (LDL-C) therapeutic goals and lipid-lowering therapy compliance in patients with acute coronary syndromes), which included 357 ACS patients, was reported that the combination of statin, dual antiplatelet therapy and betablockers were prescribed to 79.6% of patients upon discharge.10 A renin-angiotensin-aldosterone system inhibitor and a betablocker were prescribed to 67.3 and 91.8% of patients with LVEF 40%, respectively. From CAD patients only 22.3% had recommended LDL-C values of <70 mg/dl at admission. Among ACS patients who were already under high intensity statins before hospitalisation and without reaching the recommended LDL-C values, only 13.3% received additional therapy with ezetimibe at discharge.10 Adherence to statins varies between studies. The rates of adherence are usually better in RCT than observational studies/realworld settings. In Lemestra et al meta-analysis was found the statin adherence rates of 49% in observational studies and 90.3% in controlled trials.11 In the EUROASPIRE IV study of a crosssectional European ACS cohort, 85.7% were on lipid lowering medication >6 months after the event.12 Individual reasons for nonadherence concerning statin treatment after ACS have been inadequately investigated. In meta analyses of adherence, female gender, low education, high-dose treatment, polypharmacy and poor prescriber-patient relationships have been highlighted. Gencer et al13 found that the doctor's decision to stop treatment was the most prevalent reason for treatment discontinuation, followed by side effects. In the USAGE (Understanding Statin Use in America and Gaps in Patient Education) study, side effects were the primary reason for treatment discontinuation.14 Reported side effects of the statin group are mainly muscle symptoms in 7e29% of patients, but also included rhabdomyolysis, memory impairment, cataracts, renal dysfunction and diabetes. Although, placebo-controlled trials have not been able to show increased levels of side effects. 1. Conclusions Long-term follow-up of patients with ACS either by telephonebased interventions or motivational interviewing, may result in higher adherence to medical treatment compared with usual care. A certain number of unsubstantiated discontinuations seems unavoidable, but the proportion of avoidable causes for discontinuation may be reduced with duration of follow-up. Thus, the strengthening lipid lowering medication by healthcare personnel (doctors, nurses and others) on the implication of the evidencebased guidelines should be enhanced. Therefore, adherence efficacy trials and may fill the gap regarding how adherence interventions should be implemented into clinical care.
255
Declaration of conflicting interests The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Funding The author received no financial support for the research, authorship, and/or publication of this article.
References 1. Szummer K, Jernberg T, Wallentin L, et al. From Early Pharmacology to Recent Pharmacology Interventions in Acute Coronary Syndromes: JACC State-of-theArt Review. J Am Coll Cardiol. 2019;74:1618e1636. 2. Puymirat E, Simon T, Cayla G, et al. Acute myocardial infarction: changes in patient characteristics, management, and 6-month outcomes over a period of 20 years in the FAST-MI Program (French Registry of Acute ST-Elevation or NonST-Elevation Myocardial Infarction) 1995 to 2015. Circulation. 2017;136: 1908e1919. 3. Kumbhani DJ, Steg PG, Cannon CP, et al. Adherence to secondary prevention medications and four-year outcomes in outpatients with atherosclerosis. Am J Med. 2013;126:693e700. 4. Cannon CP, Blazing MA, Giugliano RP, et al, IMPROVE-IT Investigators. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387e2397. 5. Giugliano RP, Pedersen TR, Park JG, et al. FOURIER Investigators. Clinical efficacy and safety of achieving very low LDL- cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial. Lancet. 2017;390:1962e1971. 6. Schwartz GG, Steg PG, Szarek M, et al. ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379:2097e2107. 7. Mach C, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. pii: ehz455 Eur Heart J. 2019. https://doi.org/10.1093/eurheartj/ehz455 [Epub ahead of print]. 8. Boulmpou A, Kartas A, Farmakis I, et al. Motivational interviewing to support LDL-C therapeutic goals and lipid-lowering therapy compliance in patients with acute coronary syndromes (IDEAL-LDL) study: rationale and design. Hellenic J Cardiol. 2019;60:249e253. 9. Daniel H, Christian W, Robin H, Lars S, Thomas M. Statin treatment after acute coronary syndrome: Adherence and reasons for non-adherence in a randomized controlled intervention trial. Sci Rep. 2019;9:12079. 10. Farmakis I, Zafeiropoulos S, Kartas A, et al. Treatment practices and lipid profile of patients with acute coronary syndrome: results from a tertiary care hospital. Acta Cardiol. 2019 Jun 20:1e8. 11. Lemstra M, Blackburn D, Crawley A, Fung R. Proportion and risk indicators of nonadherence to statin therapy: a meta-analysis. Can J Cardiol. 2012;28: 574e580. 12. Kotseva K, Wood D, De Bacquer D, et al. EUROASPIRE IV. A European Society of Cardiology survey on the lifestyle, risk factor and therapeutic management of coronary patients from 24 European countries. Eur J Prev Cardiol. 2016;23: 636e648. 13. Gencer B, Rodondi N, Auer R, et al. Reasons for discontinuation of recommended therapies according to the patients after acute coronary syndromes. Eur J Intern Med. 2015;26:56e62. 14. Cohen JD, Brinton EA, Ito MK, Jacobson TA. Understanding Statin Use in America and Gaps in Patient Education (USAGE): an internet-based survey of 10,138 current and former statin users. J Clin Lipidol. 2012;6:208e215.
Genovefa Kolovou* Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece *
Corresponding author. Genovefa Kolovou, Onassis Cardiac Surgery Center, 356 Sygrou Ave, 176 74 Athens, Greece. Tel: þ30 210 9493520, Fax: þ30 210 9493336. E-mail address: [email protected]. 10 October 2019