Impact of statin adherence on cardiovascular disease and mortality outcomes: a systematic review
Open accessAbstract
Aims: While suboptimal adherence to statin medication has been quantified in real‐world patient settings, a better understanding of its impact is needed, particularly with respect to distinct problems of medication taking. Our aim was to synthesize current evidence on the impacts of statin adherence, discontinuation and persistence on cardiovascular disease and mortality outcomes. Methods: We conducted a systematic review of peer‐reviewed studies using a mapped search of M edline, E mbase and I nternational P harmaceutical A bstracts databases. Observational studies that met the following criteria were included: defined patient population; statin adherence exposure; defined study outcome [i.e. cardiovascular disease ( CVD ), mortality]; and reporting of statin‐specific results. Results: Overall, 28 studies were included, with 19 studies evaluating outcomes associated with statin adherence, six with statin discontinuation and three with statin persistence. Among adherence studies, the proportion of days covered was the most widely used measure, with the majority of studies reporting increased risk of CVD (statistically significant risk estimates ranging from 1.22 to 5.26) and mortality (statistically significant risk estimates ranging from 1.25 to 2.54) among non‐adherent individuals. There was greater methodological variability in discontinuation and persistence studies. However, findings of increased CVD (statistically significant risk estimates ranging from 1.22 to 1.67) and mortality (statistically significant risk estimates ranging from 1.79 to 5.00) among nonpersistent individuals were also consistently reported. Conclusions: Observational studies consistently report an increased risk of adverse outcomes associated with poor statin adherence. These findings have important implications for patients and physicians and emphasize the importance of monitoring and encouraging adherence to statin therapy.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Poor adherence to lipid-lowering medications remains a barrier in reducing the substantial global burden of cardiovascular disease.
“Despite their effectiveness in primary and secondary prevention of CVD, poor adherence to LLMs remains a barrier in reducing the substantial global burden of CVD.2,3”
From Interventions to improve adherence to lipid-lowering drugs: a systematic review and meta-analysis (2025) · cites this paper as [2]
The Introduction reports substantial poor adherence to statins, and the Abstract reports higher CVD and mortality risks among non-adherent patients. This supports poor statin adherence as a barrier to better CVD outcomes, but the review does not establish the claim for lipid-lowering medications generally or quantify its effect on the global CVD burden. No page numbers are available in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe main reason for statin non-adherence/discontinuation relates to the onset of (perceived) side effects.
“Given that the main reason for statin non-adherence/discontinuation relates to the onset of (perceived) side effects”
From Statin-associated muscle symptoms: impact on statin therapy—European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management (2015) · cites this paper as [119]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
OLSSON, A. G., McMurray, J. J. V., Thorgeirsson, G., Spaulding, C. M., Slattery, J., Pyörälà, K., Færgeman, O., Wright, R. S., Berg, K. M., Wilhelmsen, L., et al. (1994) · The Lancet · Cited by 8,467 · see citing works
Osterberg, L., & Blaschke, T. (2005) · New England Journal of Medicine · doi:10.1056/nejmra050100 · Cited by 7,974 · see citing works
Prevention of Coronary Heart Disease with Pravastatin in Men with Hypercholesterolemia
Shepherd, J., Cobbe, S. M., Ford, I., Isles, C. G., Lorimer, A. R., Macfarlane, P. W., McKillop, J. H., & Packard, C. J. (1995) · New England Journal of Medicine · doi:10.1056/nejm199511163332001 · Cited by 7,449 · see citing works
Adherence to Long-Term Therapies: Evidence for Action
Geest, S. D., & Sabate, E. J. (2003) · European Journal of Cardiovascular Nursing · doi:10.1016/s1474-5151(03)00091-4 · Cited by 6,274 · see citing works
Kirk, J. M. W., MacDonald, A., Lavender, P., Dean, J. M., & Rubin, G. (2017) · Biomedicine Hub · doi:10.1159/000480347 · Cited by 3,901 · see citing works
Update on Key Emerging Challenges in Cystic Fibrosis
Jennings, M. T., Riekert, K. A., & Boyle, M. (2014) · Medical Principles and Practice · doi:10.1159/000357646 · Cited by 3,667 · see citing works
SCANDINAVIANSIMVASTATINSURVIVAL (1994) · The Lancet · doi:10.1016/s0140-6736(94)90566-5 · Cited by 3,638 · see citing works
Pedersen, T. R. (2004) · Atherosclerosis Supplements · doi:10.1016/j.atherosclerosissup.2004.08.027 · Cited by 3,098 · see citing works
Adherence to Long‐Term Therapies: Evidence for Action
Burkhart, P. V., & Sabaté, E. (2003) · Journal of Nursing Scholarship · doi:10.1111/j.1547-5069.2003.tb00001.x · Cited by 2,526 · see citing works
Medication compliance and persistence: terminology and definitions
Cramer, J. A., Roy, A., Burrell, A., Fairchild, C. J., Fuldeore, M. J., Ollendorf, D. A., & Wong, P. K. (2008) · Value in Health · doi:10.1111/j.1524-4733.2007.00213.x · Cited by 2,220 · see citing works
Prescribing Personalized Nutrition for Cardiovascular Health: Are We Ready?
Juma, S., Imrhan, V., Vijayagopal, P., & Prasad, C. (2014) · Lifestyle Genomics · doi:10.1159/000370213 · Cited by 1,905 · see citing works
Ho, P. M., Rumsfeld, J. S., Masoudi, F. A., McClure, D. L., Plomondon, M. E., Steiner, J. F., & Magid, D. J. (2006) · Archives of Internal Medicine · doi:10.1001/archinte.166.17.1836 · Cited by 1,135 · see citing works
Rasmussen, J. N., Chong, A., & Alter, D. A. (2007) · JAMA · doi:10.1001/jama.297.2.177 · Cited by 975 · see citing works
Adherence to cardiovascular therapy: a meta-analysis of prevalence and clinical consequences
Chowdhury, R., Khan, H., Heydon, E., Shroufi, A., Fahimi, S., Moore, C., Stricker, B., Mendis, S., Hofman, A., Mant, J., et al. (2013) · European Heart Journal · doi:10.1093/eurheartj/eht295 · Cited by 931 · see citing works
Hess, L. M., Raebel, M. A., Conner, D. A., & Malone, D. C. (2006) · Annals of Pharmacotherapy · doi:10.1345/aph.1h018 · Cited by 759 · see citing works
A Checklist for Medication Compliance and Persistence Studies Using Retrospective Databases
Peterson, A. M., Nau, D. P., Cramer, J. A., Benner, J., Gwadry-Sridhar, F. H., & Nichol, M. B. (2006) · Value in Health · doi:10.1111/j.1524-4733.2006.00139.x · Cited by 638 · see citing works
Impact of Medication Therapy Discontinuation on Mortality After Myocardial Infarction
Ho, P. M., Spertus, J. A., Masoudi, F. A., Reid, K. J., Peterson, E. D., Magid, D. J., Krumholz, H. M., & Rumsfeld, J. S. (2006) · Archives of Internal Medicine · doi:10.1001/archinte.166.17.1842 · Cited by 635 · see citing works
Persistence of Use of Lipid-Lowering Medications
Avorn, J., Monette, J., Lacour, A. S., Bohn, R. L., Monane, M., Mogun, H., & LeLorier, J. (1998) · JAMA · doi:10.1001/jama.279.18.1458 · Cited by 635 · see citing works
Ho, P. M., Magid, D. J., Shetterly, S. M., Olson, K. L., Maddox, T. M., Peterson, P. N., Masoudi, F. A., & Rumsfeld, J. S. (2008) · American Heart Journal · doi:10.1016/j.ahj.2007.12.011 · Cited by 587 · see citing works
Andrade, S. E., Walker, A. M., Gottlieb, L. K., Hollenberg, N., Testa, M. A., Saperia, G., & Platt, R. (1995) · New England Journal of Medicine · doi:10.1056/nejm199504273321703 · Cited by 391 · see citing works
Suboptimal statin adherence and discontinuation in primary and secondary prevention populations
Ellis, J. J., Erickson, S. R., Stevenson, J. G., Bernstein, S. J., Stiles, R. A., & Fendrick, A. M. (2004) · Journal of General Internal Medicine · doi:10.1111/j.1525-1497.2004.30516.x · Cited by 318 · see citing works
Li, W., Wang, J., Thompson, P., Wong, S., Struthers, A. D., & MacDonald, T. M. (2002) · Heart · doi:10.1136/heart.88.3.229 · Cited by 294 · see citing works
Apparent discontinuation rates in patients prescribed lipid‐lowering drugs
Simons, L. A., Levis, G., & Simons, J. (1996) · The Medical Journal of Australia · doi:10.5694/j.1326-5377.1996.tb94138.x · Cited by 214 · see citing works
Discontinuation of Statin Therapy and Clinical Outcome After Ischemic Stroke
Colivicchi, F., Bassi, A., Santini, M., & Caltagirone, C. (2007) · Stroke · doi:10.1161/strokeaha.107.487017 · Cited by 174 · see citing works
Caetano, P. A., Lam, J. M. C., & Morgan, S. G. (2006) · Clinical Therapeutics · doi:10.1016/j.clinthera.2006.09.021 · Cited by 159 · see citing works
Ho, P. M., Magid, D. J., Masoudi, F. A., McClure, D. L., & Rumsfeld, J. S. (2006) · BMC Cardiovascular Disorders · doi:10.1186/1471-2261-6-48 · Cited by 157 · see citing works
Continuation of Statin Treatment and All-Cause Mortality
Shalev, V., Chodick, G., Silber, H., Kokia, E. S., Jan, J., & Heymann, A. D. (2009) · Archives of Internal Medicine · doi:10.1001/archinternmed.2008.552 · Cited by 151 · see citing works
Chodick, G., Shalev, V., Gerber, Y., Heymann, A. D., Silber, H., Simah, V., & Kokia, E. (2008) · Clinical Therapeutics · doi:10.1016/j.clinthera.2008.11.012 · Cited by 145 · see citing works
Beest, F. J. A. P., Termorshuizen, F., Goettsch, W., Klungel, O. H., Kastelein, J. J. P., & Herings, R. M. C. (2006) · European Heart Journal · doi:10.1093/eurheartj/ehl391 · Cited by 143 · see citing works
Discontinuation of statin therapy following an acute myocardial infarction: a population-based study
Daskalopoulou, S. S., Delaney, J. A., Filion, K. B., Brophy, J. M., Mayo, N. E., & Suissa, S. (2008) · European Heart Journal · doi:10.1093/eurheartj/ehn346 · Cited by 134 · see citing works
Tuppin, P., Neumann, A., Danchin, N., de Peretti, C., Weill, A., Ricordeau, P., & Allemand, H. (2010) · Archives of cardiovascular diseases · doi:10.1016/j.acvd.2010.05.003 · Cited by 132 · see citing works
Simpson, R. J., & Mendys, P. (2010) · Journal of clinical lipidology · doi:10.1016/j.jacl.2010.08.026 · Cited by 131 · see citing works
Blackburn, D. F., Dobson, R. T., Blackburn, J. L., Wilson, T. W., Stang, M. R., & Semchuk, W. (2005) · PubMed · Cited by 122 · see citing works
Cardiovascular Morbidity Associated with Nonadherence to Statin Therapy
Blackburn, D. F., Dobson, R. T., Blackburn, J. L., & Wilson, T. W. (2005) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1592/phco.2005.25.8.1035 · Cited by 112 · see citing works
Impact of adherence to statins on coronary artery disease in primary prevention
Bouchard, M.-H., Dragomir, A., Blais, L., Bérard, A., Pilon, D., & Perreault, S. (2007) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2006.02828.x · Cited by 101 · see citing works
Impact of better adherence to statin agents in the primary prevention of coronary artery disease
Perreault, S., Dragomir, A., Blais, L., Bérard, A., Lalonde, L., White, M., & Pilon, D. (2009) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-009-0673-0 · Cited by 95 · see citing works
Esposti, L. D., Saragoni, S., Batacchi, P., Benemei, S., Geppetti, P., Sturani, A., Buda, S., & Esposti, E. D. (2012) · Clinical Therapeutics · doi:10.1016/j.clinthera.2011.12.011 · Cited by 92 · see citing works
Corrao, G., Conti, V., Merlino, L. G., Catapano, A. L., & Mancia, G. (2010) · Clinical Therapeutics · doi:10.1016/j.clinthera.2010.02.004 · Cited by 90 · see citing works
Statin Discontinuation in High-Risk Patients: A Systematic Review of the Evidence
Sandoval, Y.-H. G., Braganza, M. V., & Daskalopoulou, S. S. (2011) · Current Pharmaceutical Design · doi:10.2174/138161211798220891 · Cited by 86 · see citing works
Compliance with lipid-lowering therapy and its impact on cardiovascular morbidity and mortality
Liberopoulos, E. N., Florentin, M., Mikhailidis, D. P., & Elisaf, M. (2008) · Expert Opinion on Drug Safety · doi:10.1517/14740330802396984 · Cited by 67 · see citing works
Vera, M. A. D., Choi, H. K., Abrahamowicz, M., Kopec, J. A., & Lacaille, D. V. (2012) · Arthritis Care & Research · doi:10.1002/acr.21643 · Cited by 67 · see citing works
Self-citationEffect of Statin Adherence on Cerebrovascular Disease in Primary Prevention
Perreault, S., Ellia, L., Dragomir, A., Côté, R., Blais, L., Bérard, A., & Lalonde, L. (2009) · The American Journal of Medicine · doi:10.1016/j.amjmed.2009.01.032 · Cited by 65 · see citing works
De Vera, M. A., Choi, H., Abrahamowicz, M., Kopec, J., Goycochea-Robles, M. V., & Lacaille, D. (2011) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2010.142455 · Cited by 64 · see citing works
Self-citationDragomir, A., Côté, R., White, M., Lalonde, L., Blais, L., Bérard, A., & Perreault, S. (2009) · Value in Health · doi:10.1111/j.1524-4733.2009.00583.x · Cited by 62 · see citing works
Adherence with statins over 8 years in a usual care setting.
Vinker, S., Shani, M., Baevsky, T., & Elhayany, A. (2008) · PubMed · Cited by 62 · see citing works
Wei, L., Fahey, T. P., & MacDonald, T. M. (2008) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2008.03212.x · Cited by 52 · see citing works
Statin adherence and mortality in patients enrolled in a secondary prevention program.
McGinnis, B., Olson, K. L., Delate, T., & Stolcpart, R. S. (2009) · PubMed · Cited by 49 · see citing works
Deambrosis, P., Saramin, C., Terrazzani, G., Scaldaferri, L., Debetto, P., Giusti, P., & Chinellato, A. (2007) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-006-0239-3 · Cited by 46 · see citing works
Evaluation of Cardiovascular Morbidity Associated with Adherence to Atorvastatin Therapy
Rublee, D. A., Chen, S., Mardekian, J., et al. (2010) · American Journal of Therapeutics · doi:10.1097/mjt.0b013e3181ee707e · Cited by 44 · see citing works
Foody, J. M., Joyce, A. T., Rudolph, A. E., Liu, L. Z., & Benner, J. S. (2008) · Current Medical Research and Opinion · doi:10.1185/03007990802203279 · Cited by 42 · see citing works
Hippisley‐Cox, J. (2005) · Heart · doi:10.1136/hrt.2005.061523 · Cited by 40 · see citing works
Impact of adherence to statins on chronic heart failure in primary prevention
Perreault, S., Dragomir, A., Blais, L., Bérard, A., Lalonde, L., & White, M. (2008) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2008.03269.x · Cited by 37 · see citing works
Statin usage and all‐cause and disease‐specific mortality in a nationwide study
Haukka, J. K., NISKANEN, L. K., Partonen, T., Lönnqvist, J. K., & Tiihonen, J. (2011) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.2255 · Cited by 36 · see citing works
Rabinowich, L., Steinvil, A., Leshem‐Rubinow, E., et al. (2012) · Heart · doi:10.1136/heartjnl-2012-302906 · Cited by 15 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Urquhart J, Vrijens B. New findings about ptaient adherence to prescribed drug dosing regimens: an introduction to pharmionics. Eur J Hosp Pharm Sci 2005; 11: 103-06.
- Howell N, Trotter R, Mottram D, Rowe P. Compliance with statins in primary care. Pharm J 2004; 272: 23-6.
Cited by
Sorted by citations
Stroes, E. S., Thompson, P. D., Corsini, A., Vladutiu, G. D., Raal, F. J., Ray, K. K., Roden, M., Stein, E., Tokgözoğlu, L., Nordestgaard, B. G., et al. (2015) · European Heart Journal · doi:10.1093/eurheartj/ehv043 · Cited by 1,443 · see citing works
Prevalence of statin intolerance: a meta-analysis
Bytyçi, I., Penson, P. E., Mikhailidis, D. P., Wong, N. D., Hernandez, A. V., Sahebkar, A., Thompson, P. D., Mazidi, M., Rysz, J., Pella, D., et al. (2022) · European Heart Journal · doi:10.1093/eurheartj/ehac015 · Cited by 481 · see citing works
Landmesser, U., Chapman, M. J., Stock, J. K., Amarenco, P., Belch, J. J. F., Borén, J., Farnier, M., Ference, B. A., Gielen, S., Graham, I., et al. (2018) · European Heart Journal · doi:10.1093/eurheartj/ehx549 · Cited by 200 · see citing works
Yao, X., Shah, N. D., Gersh, B. J., Lopez-Jimenez, F., & Noseworthy, P. A. (2020) · JAMA Network Open · doi:10.1001/jamanetworkopen.2020.25505 · Cited by 117 · see citing works
Warden, B. A., Guyton, J. R., Kovacs, A. C., Durham, J. A., Jones, L. K., Dixon, D. L., Jacobson, T. A., & Duell, P. B. (2023) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2022.09.001 · Cited by 111 · see citing works
Laufs, U., Karmann, B., & Pittrow, D. (2016) · Clinical Research in Cardiology · doi:10.1007/s00392-016-0991-z · Cited by 59 · see citing works
Mach, F., Visseren, F. L. J., Cater, N. B., Salhi, N., Soronen, J., Ray, K. K., Delgado, V., Jukema, J. W., Laufs, U., Zamorano, J.-L., et al. (2024) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2024.07.001 · Cited by 57 · see citing works
Martin-Ruiz, E., Olry-de-Labry-Lima, A., Ocaña-Riola, R., & Epstein, D. (2018) · Journal of Cardiovascular Pharmacology and Therapeutics · doi:10.1177/1074248417745357 · Cited by 45 · see citing works
Kristiansen, O., Vethe, N. T., Peersen, K., Wang Fagerland, M., Sverre, E., Prunés Jensen, E., Lindberg, M., Gjertsen, E., Gullestad, L., Perk, J., et al. (2021) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvaa076 · Cited by 27 · see citing works
Cicero, A. F. G., Morbini, M., Bove, M., D’Addato, S., Fogacci, F., Rosticci, M., & Borghi, C. (2016) · Current Medical Research and Opinion · doi:10.1080/03007995.2016.1190326 · Cited by 23 · see citing works
Interventions to improve adherence to lipid-lowering drugs: a systematic review and meta-analysis
Yow, D. K. W., Ang, W. J., Yap, H. J., Ito, S., Liu, J., Ko, J., Tan, D. S.-Y., Lorenzatti, A., & Ang, C.-S. (2025) · eClinicalMedicine · doi:10.1016/j.eclinm.2025.103270 · Cited by 5 · see citing works
- Authors
- De Vera, M. A., Bhole, V., Burns, L. C., & Lacaille, D.
- Affiliations
- Faculty of Pharmaceutical Sciences University of British Columbia Vancouver British Columbia Canada
- Arthritis Research Centre of Canada (CA)
- University of British Columbia (CA)
- ORCID
- Lacaille, Diane
- Venue
- British Journal of Clinical Pharmacology
- Publisher
- Wiley
- Published
- 2014-09-19
- Volume
- 78
- Issue
- 4
- Pages
- 684-698
- ISSN
- 0306-5251 (ISSN-L)
- 1365-2125
- PMC
- PMC4239963
- OpenAlex
- W1948458971
- Cited by
- 289
- References
- 55
- Citations by year
- 2026: 17 · 2025: 26 · 2024: 14 · 2023: 14 · 2022: 31 · 2021: 32 · 2020: 30 · 2019: 30 · 2018: 37 · 2017: 26 · 2016: 20 · 2015: 10 · 2014: 2
- FWCI
- 2.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Clinical Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Arthritis Society
- Canadian Institutes of Health Research (MOP 77605)
- Topics
- Health Sciences › Medicine › Family Practice › Medication Adherence and Compliance
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Keywords
- statin adherence, medication adherence, statin discontinuation, cardiovascular disease, mortality, proportion of days covered, lipid-lowering therapy
- MeSH terms
- Cardiovascular Diseases, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Medication Adherence
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
