The DOI matches its Crossref record; 40 of the 41 references it cites were found in a registry or an index.
A Randomized Trial of Intensive Lipid-Lowering Therapy in Calcific Aortic Stenosis
Open accessAbstract
BACKGROUND: Calcific aortic stenosis has many characteristics in common with atherosclerosis, including hypercholesterolemia. We hypothesized that intensive lipid-lowering therapy would halt the progression of calcific aortic stenosis or induce its regression. METHODS: In this double-blind, placebo-controlled trial, patients with calcific aortic stenosis were randomly assigned to receive either 80 mg of atorvastatin daily or a matched placebo. Aortic-valve stenosis and calcification were assessed with the use of Doppler echocardiography and helical computed tomography, respectively. The primary end points were change in aortic-jet velocity and aortic-valve calcium score. RESULTS: Seventy-seven patients were assigned to atorvastatin and 78 to placebo, with a median follow-up of 25 months (range, 7 to 36). Serum low-density lipoprotein cholesterol concentrations remained at 130+/-30 mg per deciliter in the placebo group and fell to 63+/-23 mg per deciliter in the atorvastatin group (P<0.001). Increases in aortic-jet velocity were 0.199+/-0.210 m per second per year in the atorvastatin group and 0.203+/-0.208 m per second per year in the placebo group (P=0.95; adjusted mean difference, 0.002; 95 percent confidence interval, -0.066 to 0.070 m per second per year). Progression in valvular calcification was 22.3+/-21.0 percent per year in the atorvastatin group, and 21.7+/-19.8 percent per year in the placebo group (P=0.93; ratio of post-treatment aortic-valve calcium score, 0.998; 95 percent confidence interval, 0.947 to 1.050). CONCLUSIONS: Intensive lipid-lowering therapy does not halt the progression of calcific aortic stenosis or induce its regression. This study cannot exclude a small reduction in the rate of disease progression or a significant reduction in major clinical end points. Long-term, large-scale, randomized, controlled trials are needed to establish the role of statin therapy in patients with calcific aortic stenosis.
Overview
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
Verification
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“several randomized trials showed no effect of statins on haemodynamic progression or AS-related clinical events152–154.”
From Calcific aortic stenosis (2016) · cites this paper as [152]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“However, three randomized clinical trials (RCTs) failed to demonstrate any significant benefit of LDL lowering with statins on the progression of AS152–154.”
From Calcific aortic stenosis (2016) · cites this paper as [152]
The cited source says what the claim attributes to it.
In the citing paper
“Several intervention studies have been performed to test the hypothesis that lipid lowering with statin medications would slow the progression of AS, however the results were generally disappointing152–154.”
From Calcific aortic stenosis (2016) · cites this paper as [152]
The cited source says what the claim attributes to it.
In the citing paper
“randomized controlled trials (RCTs) failed to demonstrate any benefit of statin therapy on retard disease progression6–8.”
From Genetic insights into causal effects of lipids and lipid-modifying targets on calcific aortic valve stenosis: a Mendelian randomized study (2025) · cites this paper as [6]
The cited source says what the claim attributes to it.
In the citing paper
“Several clinical trials evaluating statin therapy in mild to moderate AS failed to demonstrate efficacy in lipid lowering as a strategy to mitigate adverse events in the disease39–41.”
From Genomic and transcriptomic analyses of aortic stenosis enhance therapeutic target discovery and disease prediction (2026) · cites this paper as [39]
In the citing paper
“lipid-lowering therapy to delay progression of AS has been evaluated in 3 randomized controlled trials; however, all trials reported no significant benefit.[12][13][14]”
From Rare Genetic Variants in LDLR , APOB , and PCSK9 Are Associated With Aortic Stenosis (2024) · cites this paper as [12]
In the citing paper
“The SALTIRE (Scottish Aortic Stenosis and Lipid Lowering Trial, Impact on Regression) and ASTRONOMER (Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin) trials, which evaluated statin efficacy in AS, were constrained by small sample sizes (n=150 and n=269), 12,13 limited median follow-up periods (25 and 42 months), and a focus on advanced AS stages (mean peak velocity, 3.”
From Rare Genetic Variants in LDLR , APOB , and PCSK9 Are Associated With Aortic Stenosis (2024) · cites this paper as [12]
In the citing paper
“All of the clinical trials aimed to halt the progression of established AS.”
From Rare Genetic Variants in LDLR , APOB , and PCSK9 Are Associated With Aortic Stenosis (2024) · cites this paper as [12]
In the citing paper
“Second, we observed similar associations with AVR as a strict procedural outcome, which is particularly meaningful in the context of previous neutral clinical trials of lipid-lowering therapies that used AVR as the study end point.[12][13][14]”
From Rare Genetic Variants in LDLR , APOB , and PCSK9 Are Associated With Aortic Stenosis (2024) · cites this paper as [12]
In the citing paper
“Secondary prevention therapy with statins reduces the risk of recurrent stroke (by 12% per mmol/L reduction in LDL cholesterol), MI, and vascular death [459,460].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [459]
In the citing paper
“Notably, ischaemic events were reduced by 21% in the SEAS trial.”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [377]
In the citing paper
“Suggestions for an association between aortic stenosis, LDL-C and Lp(a), as well as between cholesterol and increased risk for calcification of bioprosthetic valves, were matched with early observational noncontrolled trials that showed beneficial effects of aggressive lipid lowering in slowing the progression of aortic stenosis. However, this was not confirmed in RCTs. 243,377,378”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [377]
In the citing paper
“Notably, ischaemic events were reduced by 21% in the SEAS trial.”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [377]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT
Martin Bland, J., & Altman, D. (1986) · The Lancet · doi:10.1016/s0140-6736(86)90837-8 · Cited by 47,965
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
Zoghbi, W. A., Enriquez-Sarano, M. L., Foster, E., Grayburn, P. A., Kraft, C. D., Levine, R. A., Nihoyannopoulos, P., Otto, C. M., Quiñones, M. A., Rakowski, H., et al. (2003) · Journal of the American Society of Echocardiography · doi:10.1016/s0894-7317(03)00335-3 · Cited by 4,041
PREVENTION OF CORONARY HEART DISEASE WITH PRAVASTATIN IN MEN WITH HYPERCHOLESTEROLEMIA
Hepherd, J. A. S., Obbe, S. T. M. C., Ord, I. A. F., Sles, C. H. G. I., Orimer, A. R. O. L., Acfarlane, P. E. W. M., Illop, J. A. H. M. C. K., Ackard, C. H. J. P., & Roup, S. T. G. (1995) · Cited by 3,453
Clinical Factors Associated With Calcific Aortic Valve Disease
Stewart, B. F., Siscovick, D., Lind, B. K., Gardin, J. M., Gottdiener, J. S., Smith, V. E., Kitzman, D. W., & Otto, C. M. (1997) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(96)00563-3 · Cited by 2,029
Applied Mixed Models in Medicine
Brown, H., & Presco, R. (2000) · Technometrics · doi:10.1080/00401706.2000.10485742 · Cited by 1,699
Predictors of Outcome in Severe, Asymptomatic Aortic Stenosis
Rosenhek, R., Binder, T. M., Porenta, G., Lang, I. M., Christ, G., SCHEMPER, M., Maurer, G., & Baumgartner, H. (2000) · New England Journal of Medicine · doi:10.1056/nejm200008313430903 · Cited by 1,332
Otto, C. M., Kuusisto, J., Reichenbach, D. D., Gown, A. M., & O’Brien, K. D. (1994) · Circulation · doi:10.1161/01.cir.90.2.844 · Cited by 1,315
Association of Aortic-Valve Sclerosis with Cardiovascular Mortality and Morbidity in the Elderly
Otto, C. M., Lind, B. K., Kitzman, D. W., Gersh, B. J., & Siscovick, D. S. (1999) · New England Journal of Medicine · doi:10.1056/nejm199907153410302 · Cited by 1,281
Otto, C. M., Burwash, I. G., Legget, M. E., Munt, B. I., Fujioka, M., Healy, N. L., Kraft, C. D., Miyake-Hull, C. Y., & Schwaegler, R. G. (1997) · Circulation · doi:10.1161/01.cir.95.9.2262 · Cited by 1,146
Jones, P., Kafonek, S., Laurora, I., & Hunninghake, D. (1998) · The American Journal of Cardiology · doi:10.1016/s0002-9149(97)00965-x · Cited by 1,067
Jukema, J., Bruschke, A. V., van Boven, A. J., Reiber, J., Bal, E., Zwinderman, A., Jansen, H., Boerma, G., van Rappard, F. M., & Kong, L. I. (1995) · Circulation · doi:10.1161/01.cir.91.10.2528 · Cited by 911
Callister, T. Q., Raggi, P., Cooil, B., Lippolis, N. J., & Russo, D. J. (1998) · New England Journal of Medicine · doi:10.1056/nejm199812313392703 · Cited by 681
O’Brien, K. D., Reichenbach, D. D., Marcovina, S. M., Kuusisto, J., Alpers, C. E., & Otto, C. M. (1996) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.16.4.523 · Cited by 560
Statins but Not Angiotensin-Converting Enzyme Inhibitors Delay Progression of Aortic Stenosis
Rosenhek, R., Rader, F., Loho, N., Gabriel, H., Heger, M., Klaar, U., SCHEMPER, M., Binder, T. M., Maurer, G., & Baumgartner, H. (2004) · Circulation · doi:10.1161/01.cir.0000140723.15274.53 · Cited by 428
Pitt, B., Mancini, G. B. J., Ellis, S. G., Rosman, H., Park, J.-S., & Mcgovern, M. E. (1995) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(95)00301-0 · Cited by 424
Presence of Oxidized Low Density Lipoprotein in Nonrheumatic Stenotic Aortic Valves
Olsson, M., Thyberg, J., & Nilsson, J. (1999) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.19.5.1218 · Cited by 417
Progression of Aortic Valve Calcification
Pohle, K., Maeffert, R., Ropers, D., Moshage, W. E. L., Stilianakis, N., Daniel, W. G., & Achenbach, S. S. (2001) · Circulation · doi:10.1161/hc4101.097527 · Cited by 405
Novaro, G. M., Tiong, I., Pearce, G. L., Lauer, M. S., Sprecher, D. L., & Griffin, B. P. (2001) · Circulation · doi:10.1161/hc4301.098249 · Cited by 392
Minimisation: the platinum standard for trials?
Treasure, T., & MacRae, K. D. (1998) · BMJ · doi:10.1136/bmj.317.7155.362 · Cited by 360
Influence of Lipid-Lowering Therapy on the Progression of Coronary Artery Calcification
Achenbach, S. S., Ropers, D., Pohle, K., Leber, A. W., Thilo, C., Knez, A., Menéndez, T., Maeffert, R., Kusus, M., Regenfus, M., et al. (2002) · Circulation · doi:10.1161/01.cir.0000027567.49283.ff · Cited by 337
Aronow, W. S., Ahn, C. W., Kronzon, I., & Goldman, M. E. (2001) · The American Journal of Cardiology · doi:10.1016/s0002-9149(01)01821-5 · Cited by 328
Bellamy, M., Pellikka, P. A., Klarich, K. W., Tajik, A. J., & Enriquez-Sarano, M. L. (2002) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(02)02496-8 · Cited by 320
New Insights Into the Progression of Aortic Stenosis: Implications for Secondary Prevention
Palta, S., Pai, A. M., Gill, K. S., & Pai, R. G. (2000) · Circulation · doi:10.1161/01.cir.101.21.2497 · Cited by 319
Olsson, M., Dalsgaard, C., Hægerstrand, A., Rosenqvist, M., Rydén, L., & Nilsson, J. (1994) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(94)90606-8 · Cited by 308
HMG CoA reductase inhibitor (statin) and aortic valve calcium
Shavelle, D. M., Takasu, J., Budoff, M. J., Mao, S., Zhao, X.-Q., & O’Brien, K. D. (2002) · The Lancet · doi:10.1016/s0140-6736(02)08161-8 · Cited by 264
Rates of progression of coronary calcium by electron beam tomography
Budoff, M. J., Lane, K. L., Bakhsheshi, H., Mao, S., Grassmann, B. O., Friedman, B. C., & Brundage, B. H. (2000) · The American Journal of Cardiology · doi:10.1016/s0002-9149(00)00820-1 · Cited by 256
Calcification of coronary arteries: detection and quantification with double-helix CT.
Shemesh, J., Apter, S., Rozenman, J., Lusky, A., Rath, S., Itzchak, Y., & Motro, M. (1995) · Radiology · doi:10.1148/radiology.197.3.7480756 · Cited by 165
Aortic Valve Calcification on Computed Tomography Predicts the Severity of Aortic Stenosis
Cowell, S. J., Newby, D. E., Burton, J. D., White, A. C., Northridge, D. B., Boon, N. A., & Reid, J. (2003) · Clinical Radiology · doi:10.1016/s0009-9260(03)00184-3 · Cited by 148
Self-citationProgression of valvar aortic stenosis: a long-term retrospective study
Davies, S., Gershlick, A., & Balcon, R. (1991) · European Heart Journal · doi:10.1093/oxfordjournals.eurheartj.a059815 · Cited by 143
Rate of progression of valvular aortic stenosis in adults
Faggiano, P. M., Ghizzoni, G., Sorgato, A., Sabatini, T., Simoncelli, U., Gardini, A., & Rusconi, C. (1992) · The American Journal of Cardiology · doi:10.1016/0002-9149(92)91280-h · Cited by 138
Factors leading to progression of valvular aortic stenosis
Bahler, R. C., Desser, D. R., Finkelhor, R. S., Brener, S. J., & Youssefi, M. E. (1999) · The American Journal of Cardiology · doi:10.1016/s0002-9149(99)00496-8 · Cited by 123
Peltier, M., Trojette, F., Enriquez-Sarano, M. L., Grigioni, F., Slama, M., & Tribouilloy, C. M. (2003) · The American Journal of Cardiology · doi:10.1016/s0002-9149(02)03010-2 · Cited by 120
Rallidis, L. S., Naoumova, R. P., Thompson, G. R., & Nihoyannopoulos, P. (1998) · Heart · doi:10.1136/hrt.80.6.583 · Cited by 97
Association of coronary risk factors with progression of valvular aortic stenosis in older persons
Nassimiha, D., Aronow, W. S., Ahn, C. W., & Goldman, M. E. (2001) · The American Journal of Cardiology · doi:10.1016/s0002-9149(01)01531-4 · Cited by 83
Predictors of outcome in severe, asymptomatic aortic stenosis
Rosenhek, R., Binder, T. M., & Porenta, G. (2001) · ACC Current Journal Review · doi:10.1016/s1062-1458(00)00164-1 · Cited by 46
Mautner, G. C., & Roberts, W. C. (1992) · The American Journal of Cardiology · doi:10.1016/0002-9149(92)91206-j · Cited by 38
Zhao, X.-Q., Brown, B. G., Hillger, L. A., Sacco, D., Bisson, B., Fisher, L. D., & Albers, J. J. (1993) · Circulation · doi:10.1161/01.cir.88.6.2744 · Cited by 35
Keller, C., Schmitz, H. J., Theisen, K., & Zöllner, N. (1986) · Journal of Molecular Medicine · doi:10.1007/bf01711956 · Cited by 24
Flagged first, then by citations
1 of the 41 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
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., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz455 · Cited by 8,961
ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease
Bonow, R. O., Carabello, B. A., Chatterjee, K., de Leon, A. C., Faxon, D. P., Freed, M. D., Gaasch, W. H., Lytle, B. W., Nishimura, R. A., O’Gara, P. T., et al. (2006) · Circulation · doi:10.1161/circulationaha.106.176857 · Cited by 8,487
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., et al. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.08.014 · Cited by 4,854
Otto, C. M., Nishimura, R. A., Bonow, R. O., Carabello, B. A., Erwin, J. P., Gentile, F., Jneid, H., Krieger, E. V., Mack, M., McLeod, C., et al. (2021) · Circulation · doi:10.1161/cir.0000000000000923 · Cited by 3,686
Guidelines on the management of valvular heart disease
Vahanian, A. S., Baumgartner, H., Bax, J. J., Butchart, E., Dion, R., Filippatos, G. S., Flachskampf, F., Hall, R., Iung, B., Kasprzak, J. D., et al. (2007) · European Heart Journal · doi:10.1093/eurheartj/ehl428 · Cited by 3,579
Metadata
- Authors
- Cowell, S. J., Newby, D. E., Prescott, R. J., Bloomfield, P., Reid, J., Northridge, D. B., & Boon, N. A.
- Affiliations
- Edinburgh Royal Infirmary (GB)
- University of Edinburgh (GB)
- Borders General Hospital (GB)
- Western General Hospital (GB)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2005-06-09
- Volume
- 352
- Issue
- 23
- Pages
- 2389-2397
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2117330772
- Cited by
- 1,146
- References
- 41
- Citations by year
- 2026: 46 · 2025: 52 · 2024: 57 · 2023: 37 · 2022: 47 · 2021: 44 · 2020: 59 · 2019: 38 · 2018: 39 · 2017: 52 · 2016: 52 · 2015: 37 · 2014: 65 · 2013: 64 · 2012: 55
- FWCI
- 47.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Valve Diseases and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
- Keywords
- calcific aortic stenosis, atorvastatin, statin therapy, lipid-lowering therapy, valve calcification, disease progression, aortic jet velocity, aortic valve calcium score, LDL cholesterol, hypercholesterolemia, atherosclerosis, echocardiography, CT angiography
- MeSH terms
- Atorvastatin, Anticholesteremic Agents, Aortic Valve, Aortic Valve Stenosis, Blood Flow Velocity, Calcinosis, Double-Blind Method, Heptanoic Acids, Humans, Cholesterol, LDL, Pyrroles, Echocardiography, Doppler, Treatment Failure, Disease Progression, Hydroxymethylglutaryl-CoA Reductase Inhibitors
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
