Major adverse cardiovascular events

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Major adverse cardiovascular events (MACE, or major adverse cardiac events) is a composite endpoint frequently used in cardiovascular research.[1][2] Despite widespread use of the term in clinical trials, the definitions of MACE can differ, which makes comparison of similar studies difficult.[3]

Definition

The so-called "classical 3-point MACE" is defined as a composite of nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death.[4][5] But another study defines MACE as "CVD events, admission for HF (Heart Failure), ischemic cardiovascular [CV] events, cardiac death, or MACE".[6] Yet another study defined MACE as "CV death, hospitalization for HF, or myocardial infarction (MI)".[7]

The heterogeneity of the sets defining MACE, hampering systematic reviews and meta-analyses, has been repeatedly criticized.[8][9][10]

Risk factors for MACE

Which conditions are risk factors for MACE depends on some characteristics of the investigated cohort. Established risk indicators in the general population include age, pre-existing cardiovascular disease, smoking, diabetes mellitus, elevated concentrations of triglycerides and non-HDL cholesterol concentration, reduced HDL concentration and hypertension, as, e. g., demonstrated by the Framingham Heart Study. More recently, additional risk indicators have been identified, e. g. type 2 allostatic load,[11] high-sensitivity C-reactive protein, d-dimer level,[12] renal failure[13] and altered thyroid function.[14][15][16][17]

Therapeutic interventions

Two reviews have concluded that SGLT2 inhibitors benefit patients with atherosclerotic MACE.[18][19] One of those studies defined MACE as the composite of myocardial infarction, stroke, or cardiovascular death.[18] Other studies have shown MACE to be potently predicted by levels of ceramide found in patients.[20]


References

  1. ^ Bonora BM, Avogaro A, Fadini GP (2020). "Extraglycemic Effects of SGLT2 Inhibitors: A Review of the Evidence". Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 13: 161–174. doi:10.2147/DMSO.S233538. PMC 6982447. PMID 32021362.
  2. ^ Chong WH, Yanoff LB, Andraca-Carrera E, Hai MT (2020). "Assessing the Safety of Glucose-Lowering Drugs - A New Focus for the FDA". The New England Journal of Medicine. 383 (13): 1199–1202. doi:10.1056/NEJMp2004889. PMID 32966719. S2CID 221888300.
  3. ^ Kip KE, Hollabaugh K, Marroquin OC, Williams DO (2008). "The problem with composite end points in cardiovascular studies: the story of major adverse cardiac events and percutaneous coronary intervention". Journal of the American College of Cardiology. 51 (7): 701–707. doi:10.1016/j.jacc.2007.10.034. PMID 18279733.
  4. ^ de Jong M, van der Worp HB, van der Graaf Y, Visseren FL, Westerink J (2017). "Pioglitazone and the secondary prevention of cardiovascular disease. A meta-analysis of randomized-controlled trials". Cardiovascular Diabetology. 16 (1): 134. doi:10.1186/s12933-017-0617-4. PMC 5644073. PMID 29037211.
  5. ^ Arnott C, Li Q, Kang A, Neuen BL, Bompoint S, Lam CS, Rodgers A, Mahaffey KW, Cannon CP, Perkovic V, Jardine MJ, Neal B (2020). "Sodium-Glucose Cotransporter 2 Inhibition for the Prevention of Cardiovascular Events in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis". Journal of the American Heart Association. 9 (3): e014908. doi:10.1161/JAHA.119.014908. PMC 7033896. PMID 31992158.
  6. ^ Heianza Y, Ma W, Manson JE, Rexrode KM, Qi L (2017). "Gut Microbiota Metabolites and Risk of Major Adverse Cardiovascular Disease Events and Death: A Systematic Review and Meta-Analysis of Prospective Studies". Journal of the American Heart Association. 6 (7): e004947. doi:10.1161/JAHA.116.004947. PMC 5586261. PMID 28663251.
  7. ^ Ramchand J, Patel SK, Srivastava PM, Farouque O, Burrell LM (2018). "Elevated plasma angiotensin converting enzyme 2 activity is an independent predictor of major adverse cardiac events in patients with obstructive coronary artery disease". PLOS One. 13 (6): e0198144. Bibcode:2018PLoSO..1398144R. doi:10.1371/journal.pone.0198144. PMC 5999069. PMID 29897923.
  8. ^ Poudel, I; Tejpal, C; Rashid, H; Jahan, N (30 July 2019). "Major Adverse Cardiovascular Events: An Inevitable Outcome of ST-elevation myocardial infarction? A Literature Review". Cureus. 11 (7): e5280. doi:10.7759/cureus.5280. PMC 6695291. PMID 31423405. S2CID 201040946.
  9. ^ Bonsu, JM; Guha, A; Charles, L; Yildiz, VO; Wei, L; Baker, B; Brammer, JE; Awan, F; Lustberg, M; Reinbolt, R; Miller, ED; Jneid, H; Ruz, P; Carter, RR; Milks, MW; Paskett, ED; Addison, D (18 February 2020). "Reporting of Cardiovascular Events in Clinical Trials Supporting FDA Approval of Contemporary Cancer Therapies". Journal of the American College of Cardiology. 75 (6): 620–628. doi:10.1016/j.jacc.2019.11.059. PMC 7860639. PMID 32057377.
  10. ^ Bosco, E; Hsueh, L; McConeghy, KW; Gravenstein, S; Saade, E (6 November 2021). "Major adverse cardiovascular event definitions used in observational analysis of administrative databases: a systematic review". BMC Medical Research Methodology. 21 (1): 241. doi:10.1186/s12874-021-01440-5. PMC 8571870. PMID 34742250. S2CID 243767377.
  11. ^ Robertson, T; Beveridge, G; Bromley, C (2017). "Allostatic load as a predictor of all-cause and cause-specific mortality in the general population: Evidence from the Scottish Health Survey". PLOS ONE. 12 (8): e0183297. Bibcode:2017PLoSO..1283297R. doi:10.1371/journal.pone.0183297. PMC 5559080. PMID 28813505.
  12. ^ Zhao, X; Liu, C; Zhou, P; Sheng, Z; Li, J; Zhou, J; Chen, R; Wang, Y; Chen, Y; Song, L; Zhao, H; Yan, H (2020). "Estimation of Major Adverse Cardiovascular Events in Patients With Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A Risk Prediction Score Model From a Derivation and Validation Study". Frontiers in Cardiovascular Medicine. 7: 603621. doi:10.3389/fcvm.2020.603621. PMC 7728669. PMID 33330667.
  13. ^ Neumann, Johannes T.; Thao, Le T. P.; Callander, Emily; Chowdhury, Enayet; Williamson, Jeff D.; Nelson, Mark R.; Donnan, Geoffrey; Woods, Robyn L.; Reid, Christopher M.; Poppe, Katrina K.; Jackson, Rod; Tonkin, Andrew M.; McNeil, John J. (February 2022). "Cardiovascular risk prediction in healthy older people". GeroScience. 44 (1): 403–413. doi:10.1007/s11357-021-00486-z. PMC 8810999. PMID 34762275.
  14. ^ Chaker, L; van den Berg, ME; Niemeijer, MN; Franco, OH; Dehghan, A; Hofman, A; Rijnbeek, PR; Deckers, JW; Eijgelsheim, M; Stricker, BH; Peeters, RP (6 September 2016). "Thyroid Function and Sudden Cardiac Death: A Prospective Population-Based Cohort Study". Circulation. 134 (10): 713–22. doi:10.1161/CIRCULATIONAHA.115.020789. PMID 27601558. S2CID 207711411.
  15. ^ Chaker, L; Baumgartner, C; den Elzen, WP; Collet, TH; Ikram, MA; Blum, MR; Dehghan, A; Drechsler, C; Luben, RN; Portegies, ML; Iervasi, G; Medici, M; Stott, DJ; Dullaart, RP; Ford, I; Bremner, A; Newman, AB; Wanner, C; Sgarbi, JA; Dörr, M; Longstreth WT, Jr; Psaty, BM; Ferrucci, L; Maciel, RM; Westendorp, RG; Jukema, JW; Ceresini, G; Imaizumi, M; Hofman, A; Bakker, SJ; Franklyn, JA; Khaw, KT; Bauer, DC; Walsh, JP; Razvi, S; Gussekloo, J; Völzke, H; Franco, OH; Cappola, AR; Rodondi, N; Peeters, RP; Thyroid Studies, Collaboration (November 2016). "Thyroid Function Within the Reference Range and the Risk of Stroke: An Individual Participant Data Analysis". The Journal of Clinical Endocrinology and Metabolism. 101 (11): 4270–4282. doi:10.1210/jc.2016-2255. PMC 5095234. PMID 27603906.
  16. ^ Müller, P; Dietrich, JW; Lin, T; Bejinariu, A; Binnebößel, S; Bergen, F; Schmidt, J; Müller, SK; Chatzitomaris, A; Kurt, M; Gerguri, S; Clasen, L; Klein, HH; Kelm, M; Makimoto, H (15 April 2020). "Usefulness of Serum Free Thyroxine Concentration to Predict Ventricular Arrhythmia Risk in Euthyroid Patients With Structural Heart Disease". The American Journal of Cardiology. 125 (8): 1162–1169. doi:10.1016/j.amjcard.2020.01.019. PMID 32087999. S2CID 211261823.
  17. ^ Müller, P; Leow, MK; Dietrich, JW (2022). "Minor perturbations of thyroid homeostasis and major cardiovascular endpoints-Physiological mechanisms and clinical evidence". Frontiers in Cardiovascular Medicine. 9: 942971. doi:10.3389/fcvm.2022.942971. PMC 9420854. PMID 36046184.
  18. ^ a b Zelniker TA, Wiviott SD, abatine MS (2019). "SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials". The Lancet. 393 (10166): 31–39. doi:10.1016/S0140-6736(18)32590-X. PMID 30424892. S2CID 53277899.
  19. ^ Xu D, Chandler O, Xiao H (2021). "Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) as a Primary Preventative Agent in the Healthy Individual: A Need of a Future Randomised Clinical Trial?". Frontiers in Medicine. 8: 712671. doi:10.3389/fmed.2021.712671. PMC 8419219. PMID 34497814.
  20. ^ Tippetts TS, Holland WL, Summers SA (2021). "Cholesterol - the devil you know; ceramide - the devil you don't". Trends in Pharmacological Sciences. 42 (12): 1082–1095. doi:10.1016/j.tips.2021.10.001. PMC 8595778. PMID 34750017.
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