Association between Aspirin Therapy and Clinical Outcomes in Patients with Non-Obstructive Coronary Artery Disease: A Cohort Study

In-Chang Hwang, Joo-Yeong Jeon, Younhee Kim, Hyue Mee Kim, Yeonyee E Yoon, Seung-Pyo Lee, Hyung-Kwan Kim, Dae-Won Sohn, Jidong Sung, Yong-Jin Kim, In-Chang Hwang, Joo-Yeong Jeon, Younhee Kim, Hyue Mee Kim, Yeonyee E Yoon, Seung-Pyo Lee, Hyung-Kwan Kim, Dae-Won Sohn, Jidong Sung, Yong-Jin Kim

Abstract

Background: Presence of non-obstructive coronary artery disease (CAD) is associated with increased prescription of cardiovascular preventive medications including aspirin. However, the association between aspirin therapy with all-cause mortality and coronary revascularization in this population has not been investigated.

Methods and findings: Among the cohort of individuals who underwent coronary computed tomography angiography (CCTA) from 2007 to 2011, 8372 consecutive patients with non-obstructive CAD (1-49% stenosis) were identified. Patients with statin or aspirin prescription before CCTA, and those with history of revascularization before CCTA were excluded. We analyzed the differences of all-cause mortality and a composite of mortality and late coronary revascularization (> 90 days after CCTA) between aspirin users (n = 3751; 44.8%) and non-users. During a median of 828 (interquartile range 385-1,342) days of follow-up, 221 (2.6%) mortality cases and 295 (3.5%) cases of composite endpoint were observed. Annualized mortality rates were 0.97% in aspirin users versus 1.28% in non-users, and annualized rates of composite endpoint were 1.56% versus 1.48%, respectively. Aspirin therapy was associated with significantly lower risk of all-cause mortality (adjusted HR 0.649; 95% CI 0.492-0.857; p = 0.0023), but not with the composite endpoint (adjusted HR 0.841; 95% CI 0.662-1.069; p = 0.1577). Association between aspirin and lower all-cause mortality was limited to patients with age ≥ 65 years, diabetes, hypertension, decreased renal function, and higher levels of coronary artery calcium score, low-density lipoprotein cholesterol and high-sensitivity C-reactive protein.

Conclusions: Among the patients with non-obstructive CAD documented by CCTA, aspirin is associated with lower all-cause mortality only in those with higher risk.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Selection of study population.
Fig 1. Selection of study population.
Fig 2. Risk-adjusted survival curves of aspirin…
Fig 2. Risk-adjusted survival curves of aspirin users versus non-users.
A, All-cause mortality-free survival by aspirin therapy in patients with non-obstructive coronary artery disease (1–49% stenosis). B, Composite endpoint (all-cause mortality or late coronary revascularization)-free survival by aspirin therapy. Survival analyses were performed using age, gender, comorbidities and concurrent medications as covariates.
Fig 3. Association between post-CCTA aspirin therapy…
Fig 3. Association between post-CCTA aspirin therapy and all-cause mortality in subgroups.
Risk-adjusted effects of aspirin therapy on all-cause mortality were analyzed in subgroups divided by age of 65 years, gender, presence of diabetes mellitus, presence of hypertension, and the results of CACS, LDL-C, hsCRP and GFR.
Fig 4. Association between post-CCTA aspirin therapy…
Fig 4. Association between post-CCTA aspirin therapy and the composite endpoint in subgroups.
Risk-adjusted effects of aspirin therapy on the composite of mortality and late coronary revascularization (>90 days after CCTA) were analyzed in subgroups divided by age of 65 years, gender, presence of diabetes mellitus, presence of hypertension, and the results of CACS, LDL-C, hsCRP and GFR.

References

    1. Shaw LJ, Hausleiter J, Achenbach S, Al-Mallah M, Berman DS, Budoff MJ, et al. Coronary computed tomographic angiography as a gatekeeper to invasive diagnostic and surgical procedures: results from the multicenter CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: an International Multicenter) registry. Journal of the American College of Cardiology. 2012;60(20):2103–14. 10.1016/j.jacc.2012.05.062 .
    1. Min JK, Dunning A, Lin FY, Achenbach S, Al-Mallah M, Budoff MJ, et al. Age- and sex-related differences in all-cause mortality risk based on coronary computed tomography angiography findings results from the International Multicenter CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry) of 23,854 patients without known coronary artery disease. Journal of the American College of Cardiology. 2011;58(8):849–60. 10.1016/j.jacc.2011.02.074 .
    1. Hoffmann U, Bamberg F, Chae CU, Nichols JH, Rogers IS, Seneviratne SK, et al. Coronary computed tomography angiography for early triage of patients with acute chest pain: the ROMICAT (Rule Out Myocardial Infarction using Computer Assisted Tomography) trial. Journal of the American College of Cardiology. 2009;53(18):1642–50. Epub 2009/05/02. doi: S0735-1097(09)00541-5 [pii] 10.1016/j.jacc.2009.01.052
    1. Choi EK, Choi SI, Rivera JJ, Nasir K, Chang SA, Chun EJ, et al. Coronary computed tomography angiography as a screening tool for the detection of occult coronary artery disease in asymptomatic individuals. Journal of the American College of Cardiology. 2008;52(5):357–65. 10.1016/j.jacc.2008.02.086 .
    1. Jespersen L, Hvelplund A, Abildstrom SZ, Pedersen F, Galatius S, Madsen JK, et al. Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. European heart journal. 2012;33(6):734–44. 10.1093/eurheartj/ehr331 .
    1. Hulten EA, Carbonaro S, Petrillo SP, Mitchell JD, Villines TC. Prognostic value of cardiac computed tomography angiography: a systematic review and meta-analysis. Journal of the American College of Cardiology. 2011;57(10):1237–47. 10.1016/j.jacc.2010.10.011 .
    1. Maddox TM, Stanislawski MA, Grunwald GK, Bradley SM, Ho PM, Tsai TT, et al. Nonobstructive coronary artery disease and risk of myocardial infarction. Jama. 2014;312(17):1754–63. Epub 2014/11/05. 10.1001/jama.2014.14681 .
    1. McEvoy JW, Blaha MJ, Nasir K, Yoon YE, Choi EK, Cho IS, et al. Impact of coronary computed tomographic angiography results on patient and physician behavior in a low-risk population. Arch Intern Med. 2011;171(14):1260–8. 10.1001/archinternmed.2011.204 .
    1. Cheezum MK, Hulten EA, Smith RM, Taylor AJ, Kircher J, Surry L, et al. Changes in preventive medical therapies and CV risk factors after CT angiography. JACC Cardiovascular imaging. 2013;6(5):574–81. Epub 2013/04/16. 10.1016/j.jcmg.2012.11.016 .
    1. Hulten E, Bittencourt MS, Singh A, O'Leary D, Christman MP, Osmani W, et al. Coronary artery disease detected by coronary computed tomographic angiography is associated with intensification of preventive medical therapy and lower low-density lipoprotein cholesterol. Circ Cardiovasc Imaging. 2014;7(4):629–38. Epub 2014/06/08. 10.1161/CIRCIMAGING.113.001564 .
    1. Collaborative overview of randomised trials of antiplatelet therapy--I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists' Collaboration. BMJ. 1994;308(6921):81–106.
    1. Antithrombotic Trialists C. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002;324(7329):71–86.
    1. Antithrombotic Trialists C, Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373(9678):1849–60. 10.1016/S0140-6736(09)60503-1
    1. Hwang IC, Jeon JY, Kim Y, Kim HM, Yoon YE, Lee SP, et al. Statin therapy is associated with lower all-cause mortality in patients with non-obstructive coronary artery disease. Atherosclerosis. 2015;239(2):335–42. Epub 2015/02/16. 10.1016/j.atherosclerosis.2015.01.036 .
    1. Kwon S. Payment system reform for health care providers in Korea. Health Policy Plan. 2003;18(1):84–92. .
    1. Lee CH, Kim K, Hyun MK, Jang EJ, Lee NR, Yim JJ. Use of inhaled corticosteroids and the risk of tuberculosis. Thorax. 2013;68(12):1105–13. Epub 2013/06/12. 10.1136/thoraxjnl-2012-203175 .
    1. Kim L, Kim JA, Kim S. A guide for the utilization of Health Insurance Review and Assessment Service National Patient Samples. Epidemiology and health. 2014;36:e2014008 Epub 2014/08/01. 10.4178/epih/e2014008
    1. Hulten E, Bittencourt MS, Ghoshhajra B, O'Leary D, Christman MP, Blaha MJ, et al. Incremental prognostic value of coronary artery calcium score versus CT angiography among symptomatic patients without known coronary artery disease. Atherosclerosis. 2014;233(1):190–5. Epub 2014/02/18. 10.1016/j.atherosclerosis.2013.12.029 .
    1. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. Journal of the American College of Cardiology. 1990;15(4):827–32. .
    1. Miller JM, Rochitte CE, Dewey M, Arbab-Zadeh A, Niinuma H, Gottlieb I, et al. Diagnostic performance of coronary angiography by 64-row CT. N Engl J Med. 2008;359(22):2324–36. 10.1056/NEJMoa0806576 .
    1. Min JK, Shaw LJ, Devereux RB, Okin PM, Weinsaft JW, Russo DJ, et al. Prognostic value of multidetector coronary computed tomographic angiography for prediction of all-cause mortality. Journal of the American College of Cardiology. 2007;50(12):1161–70. 10.1016/j.jacc.2007.03.067 .
    1. Cheng V, Berman D, Rozanski A, Dunning A, Achenbach S, Al Khdair D, et al. Performance of the traditional age, sex, and angina typicality-based approach for estimating pretest probability of angiographically significant coronary artery disease in patients undergoing coronary computed tomography angiography: results from the multinational coronary CT angiography evaluation for clinical outcomes: an international multicenter registry (CONFIRM). Circulation. 2011;124(22):2423–32. 10.1161/CIRCULATIONAHA.111.039255
    1. Matthys F, De Backer T, De Backer G, Stichele RV. Review of guidelines on primary prevention of cardiovascular disease with aspirin: how much evidence is needed to turn a tanker? European journal of preventive cardiology. 2014;21(3):354–65. Epub 2013/04/24. 10.1177/2047487312472077 .
    1. Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren M, et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). European heart journal. 2012;33(13):1635–701. 10.1093/eurheartj/ehs092 .
    1. Vandvik PO, Lincoff AM, Gore JM, Gutterman DD, Sonnenberg FA, Alonso-Coello P, et al. Primary and secondary prevention of cardiovascular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e637S–68S. Epub 2012/02/15. 10.1378/chest.11-2306
    1. Pearson TA, Blair SN, Daniels SR, Eckel RH, Fair JM, Fortmann SP, et al. AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update: Consensus Panel Guide to Comprehensive Risk Reduction for Adult Patients Without Coronary or Other Atherosclerotic Vascular Diseases. American Heart Association Science Advisory and Coordinating Committee. Circulation. 2002;106(3):388–91. .
    1. Seshasai SR, Wijesuriya S, Sivakumaran R, Nethercott S, Erqou S, Sattar N, et al. Effect of aspirin on vascular and nonvascular outcomes: meta-analysis of randomized controlled trials. Arch Intern Med. 2012;172(3):209–16. Epub 2012/01/11. 10.1001/archinternmed.2011.628 .
    1. Bartolucci AA, Tendera M, Howard G. Meta-analysis of multiple primary prevention trials of cardiovascular events using aspirin. The American journal of cardiology. 2011;107(12):1796–801. Epub 2011/04/13. 10.1016/j.amjcard.2011.02.325 .
    1. Sutcliffe P, Connock M, Gurung T, Freeman K, Johnson S, Ngianga-Bakwin K, et al. Aspirin in primary prevention of cardiovascular disease and cancer: a systematic review of the balance of evidence from reviews of randomized trials. PloS one. 2013;8(12):e81970 Epub 2013/12/18. 10.1371/journal.pone.0081970
    1. Ikeda Y, Shimada K, Teramoto T, Uchiyama S, Yamazaki T, Oikawa S, et al. Low-dose aspirin for primary prevention of cardiovascular events in Japanese patients 60 years or older with atherosclerotic risk factors: a randomized clinical trial. Jama. 2014;312(23):2510–20. Epub 2014/11/18. 10.1001/jama.2014.15690 .
    1. Hennekens CH, DeMets DL. Prevention: Aspirin in primary prevention needs individual judgements. Nat Rev Cardiol. 2014;11(8):438–40. Epub 2014/06/25. 10.1038/nrcardio.2014.88 .
    1. Miedema MD, Duprez DA, Misialek JR, Blaha MJ, Nasir K, Silverman MG, et al. Use of coronary artery calcium testing to guide aspirin utilization for primary prevention: estimates from the multi-ethnic study of atherosclerosis. Circ Cardiovasc Qual Outcomes. 2014;7(3):453–60. Epub 2014/05/08. 10.1161/CIRCOUTCOMES.113.000690 .
    1. van Kruijsdijk RC, Visseren FL, Ridker PM, Dorresteijn JA, Buring JE, van der Graaf Y, et al. Individualised prediction of alternate-day aspirin treatment effects on the combined risk of cancer, cardiovascular disease and gastrointestinal bleeding in healthy women. Heart. 2014. Epub 2014/12/06. 10.1136/heartjnl-2014-306342 .
    1. Blaha MJ, Budoff MJ, DeFilippis AP, Blankstein R, Rivera JJ, Agatston A, et al. Associations between C-reactive protein, coronary artery calcium, and cardiovascular events: implications for the JUPITER population from MESA, a population-based cohort study. Lancet. 2011;378(9792):684–92. 10.1016/S0140-6736(11)60784-8
    1. Emerging Risk Factors C, Kaptoge S, Di Angelantonio E, Pennells L, Wood AM, White IR, et al. C-reactive protein, fibrinogen, and cardiovascular disease prediction. N Engl J Med. 2012;367(14):1310–20. 10.1056/NEJMoa1107477 .
    1. Tonelli M, Muntner P, Lloyd A, Manns B, Klarenbach S, Pannu N, et al. Risk of coronary events in people with chronic kidney disease compared with those with diabetes: a population-level cohort study. Lancet. 2012;380(9844):807–14. Epub 2012 Jun 19. 10.1016/S0140-6736(12)60572-8 PubMed Central PMCID: PMC22717317.
    1. Hayden M, Pignone M, Phillips C, Mulrow C. Aspirin for the primary prevention of cardiovascular events: a summary of the evidence for the U.S. Preventive Services Task Force. Annals of internal medicine. 2002;136(2):161–72. .
    1. Goldstein LB, Adams R, Alberts MJ, Appel LJ, Brass LM, Bushnell CD, et al. Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council: cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation. 2006;113(24):e873–923. Epub 2006/06/21. 10.1161/01.STR.0000223048.70103.F1 .
    1. Adams RJ, Albers G, Alberts MJ, Benavente O, Furie K, Goldstein LB, et al. Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack. Stroke; a journal of cerebral circulation. 2008;39(5):1647–52. Epub 2008/03/07. 10.1161/STROKEAHA.107.189063
    1. Furie KL, Kasner SE, Adams RJ, Albers GW, Bush RL, Fagan SC, et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the american heart association/american stroke association. Stroke; a journal of cerebral circulation. 2011;42(1):227–76. Epub 2010/10/23. 10.1161/STR.0b013e3181f7d043 .
    1. Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis. 2008;25(5):457–507. Epub 2008/05/15. 10.1159/000131083 .
    1. Diener HC, Bogousslavsky J, Brass LM, Cimminiello C, Csiba L, Kaste M, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet. 2004;364(9431):331–7. Epub 2004/07/28. 10.1016/S0140-6736(04)16721-4 .
    1. Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006;354(16):1706–17. 10.1056/NEJMoa060989 .
    1. Benavente OR, Hart RG, McClure LA, Szychowski JM, Coffey CS, Pearce LA. Effects of clopidogrel added to aspirin in patients with recent lacunar stroke. The New England journal of medicine. 2012;367(9):817–25. Epub 2012/08/31. 10.1056/NEJMoa1204133
    1. Pen A, Yam Y, Chen L, Dennie C, McPherson R, Chow BJ. Discordance between Framingham Risk Score and atherosclerotic plaque burden. European heart journal. 2013;34(14):1075–82. 10.1093/eurheartj/ehs473 .

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