Statins for the primary prevention of cardiovascular diseases: An Asian real-world perspective.

There are relatively few reliable data on statins for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) among the elderly, and even less among the Asian population, as reported by Lin et al. [ [1] Lin Y.W. Wang C.C. Wu C.C. Hsu Y.T. Lin F.J. Effectiveness of statins for the primary prevention of cardiovascular disease in the Asian elderly population. Int. J. Cardiol. 2022; https://doi.org/10.1016/j.ijcard.2022.11.031 Abstract Full Text Full Text PDF Scopus (1) Google Scholar ]. Despite the substantial decline in the burden of ASCVDs during the past decades, elderly and women are still often under-represented in cardiovascular randomized clinical trials (RCTs), implying that current recommendations for the management of ASCVD do not adequately address these populations [ [2] Vitale C. Fini M. Spoletini I. Lainscak M. Seferovic P. Rosano G.M.C. Under-representation of elderly and women in clinical trials. Int. J. Cardiol. 2017; 232: 216-221https://doi.org/10.1016/j.ijcard.2017.01.018 Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar , [3] Maggioni A.P. Orso F. Calabria S. Rossi E. Cinconze E. Baldasseroni S. Martini N. The real-world evidence of heart failure: findings from 41 413 patients of the ARNO database. Eur. J. Heart Fail. 2016; 18 (Epub 2016 Jan 11): 402-410https://doi.org/10.1002/ejhf.471 Crossref PubMed Scopus (114) Google Scholar ]. In addition, several real-world studies have assessed statins for primary prevention among the Western older population, but results seem to be inconsistent and are not generalizable to an Asian population. From the metanalyses of both RCTs and observational studies investigating the effectiveness of statins for primary prevention using age-specific outcome data, results are encouraging, but still characterized by methodological limits [ [4] Ridker P.M. Lonn E. Paynter N.P. Glynn R. Yusuf S. Primary prevention with statin therapy in the elderly: new Meta-analyses from the contemporary JUPITER and HOPE-3 randomized trials. Circulation. 2017; 135: 1979-1981https://doi.org/10.1161/circulationaha.117.028271 Crossref PubMed Scopus (75) Google Scholar , [5] Awad K. Mohammed M. Zaki M.M. Abushouk A.I. Lip G.Y.H. Blaha M.J. Lavie C.J. Toth P.P. Jukema J.W. Sattar N. Banach M. Association of statin use in older people primary prevention group with risk of cardiovascular events and mortality: a systematic review and meta-analysis of observational studies. BMC Med. 2021; 19: 139https://doi.org/10.1186/s12916-021-02009-1 Crossref PubMed Scopus (13) Google Scholar ]. Current international guidelines [ 6 Pearson G.J. Thanassoulis G. Anderson T.J. Barry A.R. Couture P. Dayan N. Francis G.A. Genest J. Grégoire J. Grover S.A. Gupta M. Hegele R.A. Lau D. Leiter L.A. Leung A.A. Lonn E. Mancini G.B.J. Manjoo P. McPherson R. Ngui D. Piché M.E. Poirier P. Sievenpiper J. Stone J. Ward R. Wray W. 2021 Canadian cardiovascular society guidelines for the Management of Dyslipidemia for the prevention of cardiovascular disease in adults. Can. J. Cardiol. 2021; 37: 1129-1150https://doi.org/10.1016/j.cjca.2021.03.016 Abstract Full Text Full Text PDF PubMed Scopus (192) Google Scholar , 7 Arnett D.K. Blumenthal R.S. Albert M.A. Buroker A.B. Goldberger Z.D. Hahn E.J. Himmelfarb C.D. Khera A. Lloyd-Jones D. McEvoy J.W. Michos E.D. Miedema M.D. Muñoz D. Smith Jr., S.C. Virani S.S. Williams Sr., K.A. Yeboah J. Ziaeian B. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. J. Am. Coll. Cardiol. 2019; 74: e177-e232https://doi.org/10.1016/j.jacc.2019.03.010 Crossref PubMed Scopus (847) Google Scholar , 8 Visseren F.L.J. Mach F. Smulders Y.M. Carballo D. Koskinas K.C. Bäck M. Benetos A. Biffi A. Boavida J.M. Capodanno D. Cosyns B. Crawford C. Davos C.H. Desormais I. Di Angelantonio E. Franco O.H. Halvorsen S. Hobbs F.D.R. Hollander M. Jankowska E.A. Michal M. Sacco S. Sattar N. Tokgozoglu L. Tonstad S. Tsioufis K.P. van Dis I. van Gelder I.C. Wanner C. Williams B. 2021 ESC guidelines on cardiovascular disease prevention in clinical practice. Eur. Heart J. 2021; 42: 3227-3337https://doi.org/10.1093/eurheartj/ehab484 Crossref PubMed Scopus (1436) Google Scholar , 9 Grundy S.M. Stone N.J. Bailey A.L. Beam C. Birtcher K.K. Blumenthal R.S. Braun L.T. de Ferranti S. Faiella-Tommasino J. Forman D.E. Goldberg R. Heidenreich P.A. Hlatky M.A. Jones D.W. Lloyd-Jones D. Lopez-Pajares N. Ndumele C.E. Orringer C.E. Peralta C.A. Saseen J.J. Smith S.C. Sperling L. Virani S.S. Yeboah J. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the Management of Blood Cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. J. Am. Coll. Cardiol. 2019; 73: 3168-3209https://doi.org/10.1016/j.jacc.2018.11.002 Crossref PubMed Scopus (824) Google Scholar , 10 Mach F. Baigent C. Catapano A.L. Koskinas K.C. Casula M. Badimon L. Chapman M.J. De Backer G.G. Delgado V. Ference B.A. Graham I.M. Halliday A. Landmesser U. Mihaylova B. Pedersen T.R. Riccardi G. Richter D.J. Sabatine M.S. Taskinen M.-R. Tokgozoglu L. Wiklund O. Group ESD 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European atherosclerosis society (EAS). Eur. Heart J. 2019; 41: 111-188https://doi.org/10.1093/eurheartj/ehz455 Crossref Scopus (1) Google Scholar ] recommend statin initiation in high-risk primary prevention conditions when a previous ASCVD event is absent, but a gap between RCTs and real-world practice still exists. In this context of uncertainty regarding the benefit/risk profile of statins used in the primary prevention of the elderly, Lin and colleagues' [ [1] Lin Y.W. Wang C.C. Wu C.C. Hsu Y.T. Lin F.J. Effectiveness of statins for the primary prevention of cardiovascular disease in the Asian elderly population. Int. J. Cardiol. 2022; https://doi.org/10.1016/j.ijcard.2022.11.031 Abstract Full Text Full Text PDF Scopus (1) Google Scholar ] aimed to assess the effectiveness of statins for the primary prevention of ASCVD in an Asian older population. They carried out a retrospective study based on the record linkage of different national Taiwanese databases, and identified the population aged 65 and older without a history of ASCVD, from 2008 and 2015. It is worth noticing that women accounted for the 64% of the total sample, documenting once again how large is the gap between RCTs and the real clinical practice in terms of demographics of the study populations. At a median follow-up of 4.8 years, Lin et al. [ [1] Lin Y.W. Wang C.C. Wu C.C. Hsu Y.T. Lin F.J. Effectiveness of statins for the primary prevention of cardiovascular disease in the Asian elderly population. Int. J. Cardiol. 2022; https://doi.org/10.1016/j.ijcard.2022.11.031 Abstract Full Text Full Text PDF Scopus (1) Google Scholar ] found that statin use was associated with a significant reduction of major adverse cardiac events (MACE) and broadly-defined MACE (−25%), and of all-cause mortality (−21%) without any heterogeneity of effect observed across the subgroups stratified by age, sex, diabetes status and baseline low-density lipoprotein-cholesterol (LDL-C) levels. The Lin's study has some strengths [ [1] Lin Y.W. Wang C.C. Wu C.C. Hsu Y.T. Lin F.J. Effectiveness of statins for the primary prevention of cardiovascular disease in the Asian elderly population. Int. J. Cardiol. 2022; https://doi.org/10.1016/j.ijcard.2022.11.031 Abstract Full Text Full Text PDF Scopus (1) Google Scholar ]. First, it originates from the record linkage of several national databases (i.e., hospital, insurance, registries of catastrophic illness and death causes), which allowed to analyze laboratory data, social history and other in-hospital data, comorbidities, co-medications and causes of death. This allowed the identification of a large sample of patients that was truly representative of the population at high risk for ASCVD (i.e., high rate of females and high LDL-C levels [ [7] Arnett D.K. Blumenthal R.S. Albert M.A. Buroker A.B. Goldberger Z.D. Hahn E.J. Himmelfarb C.D. Khera A. Lloyd-Jones D. McEvoy J.W. Michos E.D. Miedema M.D. Muñoz D. Smith Jr., S.C. Virani S.S. Williams Sr., K.A. Yeboah J. Ziaeian B. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. J. Am. Coll. Cardiol. 2019; 74: e177-e232https://doi.org/10.1016/j.jacc.2019.03.010 Crossref PubMed Scopus (847) Google Scholar , [9] Grundy S.M. Stone N.J. Bailey A.L. Beam C. Birtcher K.K. Blumenthal R.S. Braun L.T. de Ferranti S. Faiella-Tommasino J. Forman D.E. Goldberg R. Heidenreich P.A. Hlatky M.A. Jones D.W. Lloyd-Jones D. Lopez-Pajares N. Ndumele C.E. Orringer C.E. Peralta C.A. Saseen J.J. Smith S.C. Sperling L. Virani S.S. Yeboah J. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the Management of Blood Cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. J. Am. Coll. Cardiol. 2019; 73: 3168-3209https://doi.org/10.1016/j.jacc.2018.11.002 Crossref PubMed Scopus (824) Google Scholar , [10] Mach F. Baigent C. Catapano A.L. Koskinas K.C. Casula M. Badimon L. Chapman M.J. De Backer G.G. Delgado V. Ference B.A. Graham I.M. Halliday A. Landmesser U. Mihaylova B. Pedersen T.R. Riccardi G. Richter D.J. Sabatine M.S. Taskinen M.-R. Tokgozoglu L. Wiklund O. Group ESD 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European atherosclerosis society (EAS). Eur. Heart J. 2019; 41: 111-188https://doi.org/10.1093/eurheartj/ehz455 Crossref Scopus (1) Google Scholar ]), and to overcome some limitations of the use of only administrative data (e.g., adherence to drugs privately purchased, and the effect of time-varying LDL-C levels). Second, the sample was analyzed within a long observation period (from 2008 to 2017), by applying models (i.e., propensity score and marginal structure) to adjust for potential confounding variables, especially the annual LDL-C levels. Moreover, the intrinsic weakness of the observational nature of the study was mitigated by several sensitivity analyses, which confirmed the main messages of the primary analyses. The study presents also some limitations related to the observational nature and secondary use of the databases (i.e., absence of some clinical variables, including safety data, and sample size insufficient to stratify by several CVD risk factors), and to the exclusive Asian origin of the population, which prevents from generalizing the results. Nevertheless, the latter can be considered, at the same time, a strength, due to the very poor literature about the Asian population.