44 results on '"Collins, R."'
Search Results
2. Body-mass index, abdominal adiposity, and cardiovascular risk Reply
- Author
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Wormser, D, Di Angelantonio, E, Sattar, N, Collins, R, Thompson, S, Danesh, J, and Collaboratio, E
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- 2011
3. Statins and diabetes - Reply
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Kearney, P, Keech, A, Simes, J, Collins, R, Baigent, C, and Collaboration, CTT
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- 2008
4. COMMIT/CCS-2 studies - Authors' reply
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Chen, Z, Collins, R, Peto, R, and collaboration, COMMITC-2
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business.industry ,Medicine ,General Medicine ,Commit ,business ,Law and economics - Published
- 2006
5. Authors' reply [5]
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Chen, Z, Collins, R, Peto, R, Xie, J, Jiang, L, and Liu, L
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- 2006
6. Clopidogrel and metoprolol in myocardial infarction - Reply
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Chen, Z, Collins, R, Peto, R, Xie, J, Jiang, L, and Liu, L
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- 2006
7. Efficacy and safety of cholesterol-lowering treatment - Reply
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Baigent, C, Keech, A, Kearney, P, Collins, R, Simes, J, and Collaboration, CTT
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- 2006
8. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- Author
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EBCTCG, Abe, O., Abe, R., Enomoto, K., Kikuchi, K., Koyama, H., Masuda, H., Nomura, Y., Sakai, K., Sugimachi, K., Tominaga, T., Uchino, J., Yoshida, M., Haybittle, Jl, Davies, C., Harvey, Vj, Holdaway, Tm, Kay, Rg, Mason, Bh, Forbes, Jf, Wilcken, N., Gnant, M., Jakesz, R., Ploner, M., Yosef, Hma, Focan, C., Lobelle, Jp, Peek, U., Oates, Gd, Powell, J., Durand, M., Mauriac, L., Di Leo, A., Dolci, S., Piccart, Mj, Masood, Mb, Parker, D., Price, Jj, Hupperets, Psgj, Jackson, S., Ragaz, J., Berry, D., Broadwater, G., Cirrincione, C., Muss, H., Norton, L., Weiss, Rb, Abu-Zahra, Ht, Portnoj, Sm, Baum, M., Cuzick, J., Houghton, J., Riley, D., Gordon, Nh, Davis, Hl, Beatrice, A., Mihura, J., Naja, A., Lehingue, Y., Romestaing, P., Dubois, Jb, Delozier, T., Mace-Lesec H, J., Rambert, P., Andrysek, O., Barkmanova, J., Owen, Jr, Meier, P., Howell, A., Ribeiro, Gc, Swindell, R., Alison, R., Boreham, J., Clarke, M., Collins, R., Darby, S., Elphinstone, P., Evans, V., Godwin, J., Gray, R., Harwood, C., Hicks, C., James, S., Mackinnon, E., Mcgale, P., Mchugh, T., Mead, G., Peto, R., Wang, Y., Albano, J., Oliveira, Cf, Gervasio, H., Gordilho, J., Johansen, H., Mouridsen, Ht, Gelman, Rs, Harris, Jr, Henderson, Ic, Shapiro, Cl, Andersen, Kw, Axelsson, Ck, Blichert-Toft, M., Moller, S., Overgaard, J., Overgaard, M., Rose, C., Cartensen, B., Palshof, T., Trampisch, Hj, Dalesio, O., Vries, Ege, Rodenhuis, S., Tinteren, H., Comis, Rl, Davidson, Ne, Robert, N., Sledge, G., Tormey, Dc, Wood, W., Cameron, D., Chetty, U., Forrest, P., Jack, W., Rossbach, J., Klijn, Jgm, Treurniet-Donker, Ad, Putten, Wlj, Costa, A., Veronesi, U., Bartelink, H., Duchateau, L., Legrand, C., Sylvester, R., Hage, Ja, Velde, Cjh, Cunningham, Mp, Catalano, R., Creech, Rh, Bonneterre, J., Fargeot, P., Fumoleau, P., Kerbrat, P., Namer, M., Jonat, W., Kaufmann, M., Schumacher, M., Minckwitz, G., Bastert, G., Rauschecker, H., Sauer, R., Sauerbrei, W., Schauer, A., Schryver, A., Vakaet, L., Belfiglio, M., Nicolucci, A., Pellegrini, F., Sacco, M., Valentini, M., Mcardle, Cs, Smith, Dc, Galligioni, E., Boccardo, F., Rubagotti, A., Dent, Dm, Gudgeon, Ca, Hacking, A., Erazo, A., Medina, Jy, Izuo, M., Morishita, Y., Takei, H., Fentiman, Is, Hayward, Jl, Rubens, Rd, Skilton, D., Graeff, H., Janicke, F., Meisner, C., Scheurlen, H., Fournier, D., Dafni, U., Fountzilas, G., Klefstrom, P., Blomqvist, C., Saarto, T., Margreiter, R., Asselain, B., Salmon, Rj, Vilcoq, Jr, Rodrigo Arriagada, Hill, C., Laplanche, A., Le, Mg, Spielmann, M., Bruzzi, P., Montanaro, E., Rosso, R., Sertoli, MR, Venturini, M., Amadori, D., Benraadt, J., Kooi, M., Velde, Ao, Dongen, Ja, Vermorken, Jb, Castiglione, M., Cavalli, F., Coates, A., Collins, J., Forbes, J., Gelber, Rd, Goldhirsch, A., Lindtner, J., Price, Kn, Rudenstam, Cm, Senn, Hj, Bliss, Jm, Chilvers, Ced, Coombes, Rc, Hall, E., Marty, M., Borovik, R., Brufman, G., Hayat, H., Robinson, E., Wigler, N., Bonadonna, G., Camerini, T., Palo, G., Del Vecchio, M., Formelli, F., Valagussa, P., Martoni, A., Pannuti, F., Cocconi, G., Colozza, A., Camisa, R., Aogi, K., Takashima, S., Ikeda, T., Inokuchi, K., Sawa, K., Sonoo, H., Korzeniowski, S., Skolyszewski, J., Ogawa, M., Yamashita, J., Bonte, J., Christiaens, R., Paridaens, R., Den Boegart, W., Martin, P., Romain, S., Hakes, T., Hudis, Ca, Wittes, R., Giokas, G., Kondylis, D., Lissaios, B., La Huerta, R., Sainz, Mg, Altemus, R., Cowan, K., Danforth, D., Lichter, A., Lippman, M., O Shaughnessy, J., Pierce, Lj, Steinberg, S., Venzon, D., Zujewski, J., Paradiso, A., Lena, M., Schittulli, F., Myles, Jd, Pater, Jl, Pritchard, Ki, Anderson, S., Bass, G., Brown, A., Bryant, J., Costantino, J., Dignam, J., Fisher, B., Redmond, C., Wieand, S., Wolmark, N., Jackson, Im, Palmer, Mk, Ingle, Jn, Suman, Vj, Bengtsson, No, Jonsson, H., Larsson, Lg, Lythgoe, Jp, Kissin, M., Erikstein, B., Hannisdal, E., Jacobsen, Ab, Varhaug, Je, Gundersen, S., Hauer-Jensen, M., Host, H., Nissen-Meyer, R., Blamey, Rw, Mitchell, Ak, Morgan, Dal, Robertson, Jfr, Di Palma, M., Mathe, G., Misset, Jl, Clark, Rm, Levine, M., Morimoto, K., Takatsuka, Y., Crossley, E., Harris, A., Talbot, D., Taylor, M., Di Blasio, B., Ivanov, V., Semiglazov, V., Brockschmidt, J., Cooper, MR, Ueo, H., Falkson, Ci, A Hern, R., Ashley, S., Powles, Tj, Smith, Ie, Yarnold, Jr, Gazet, Jc, Cocoran, N., Deshpande, N., Di Martino, L., Douglas, P., Lindtner, A., Notter, G., Bryant, Ajs, Ewing, Gh, Firth, La, Krushen-Kosloski, Jl, Foster, L., George, Wd, Stewart, Hj, Stroner, P., Malmstrom, P., Moller, Tr, Ryden, S., Tengrup, I., Tennvall-Nittby, L., Carstenssen, J., Dufmats, M., Hatschek, T., Nordenskjold, B., Soderberg, M., Carpenter, Jt, Albain, K., Crowley, J., Green, S., Martino, S., Osborne, Ck, Ravdin, Pm, Glas, U., Johansson, U., Rutqvist, Le, Singnomklao, T., Wallgren, A., Maibach, R., Thurlimann, B., Brenner, H., Hercbergs, A., Yoshimoto, M., Deboer, G., Paterson, Ahg, Meakin, Jw, Panzarella, T., Shan, Y., Shao, Yf, Wang, X., Zhao, Db, Chen, Zm, Pan, Hc, Bahi, J., Reid, M., Spittle, M., Deutsch, Gp, Senanayake, F., Kwong, Dlw, Bianco, Ar, Carlomagno, C., Laurentiis, M., Placido, S., Buzdar, Au, Smith, T., Bergh, J., Holmberg, L., Liljegren, G., Nilsson, J., Seifert, M., Sevelda, P., Zielinsky, Cc, Buchanan, Rb, Cross, M., Royle, Gt, Dunn, Ja, Hills, Rk, Lee, M., Morrison, Jm, Spooner, D., Litton, A., Chlebowski, Rt, Caffier, H., Faculteit Medische Wetenschappen/UMCG, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Early Breast Cancer Trialists' Collaborative, Group, DE LAURENTIIS, Michelino, and DE PLACIDO, Sabino
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Oncology ,medicine.medical_specialty ,Antineoplastic Agents, Hormonal ,DEATHS ,Ovariectomy ,Antineoplastic Agents ,Breast Neoplasms ,Aged ,Anthracyclines ,Antineoplastic Combined Chemotherapy Protocols ,Cause of Death ,Chemotherapy, Adjuvant ,Female ,Humans ,Middle Aged ,Neoplasm Metastasis ,Neoplasm Recurrence, Local ,Ovary ,Randomized Controlled Trials as Topic ,Receptors, Estrogen ,Survival Rate ,Tamoxifen ,Medicine (all) ,Breast cancer ,MammaPrint ,Internal medicine ,Receptors ,medicine ,Chemotherapy ,TAMOXIFEN ,skin and connective tissue diseases ,Survival rate ,Adjuvant ,Gynecology ,Hormonal ,medicine.diagnostic_test ,Oncotype DX Breast Cancer Assay ,business.industry ,General Medicine ,medicine.disease ,Estrogen ,Neoplasm Recurrence ,Local ,Hormonal therapy ,Oncotype DX ,business ,medicine.drug ,Epirubicin - Abstract
Background Quinquennial overviews (1985–2000) of the randomised trials in early breast cancer have assessed the 5 year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxorubicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modern aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50–69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0·0001 for recurrence, 2p For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age ( These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1–2 years of tamoxifen versus none (33 000); and about 5 years versus 1–2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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- 2005
9. Large-scale test of hypothesised associations between the angiotensin-converting-enzyme insertion/deletion polymorphism and myocardial infarction in about 5000 cases and 6000 controls. International Studies of Infarct Survival (ISIS) Collaborators
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Keavney, B, McKenzie, C, Parish, S, Palmer, A, Clark, S, Youngman, L, Delépine, M, Lathrop, M, Peto, R, and Collins, R
- Abstract
BACKGROUND: The original report of a possible association between myocardial infarction and the insertion/deletion (I/D) polymorphism of the gene for the angiotensin-1-converting enzyme (ACE) indicated a risk ratio for myocardial infarction with the DD genotype of 1.34 (95% CI 1.05-1.70), and the association was claimed to be particularly strong in a retrospectively defined low-risk subgroup (3.2 [95% CI 1.7-5.9). Subsequent investigations reached varying conclusions, but all were small, and much larger studies were needed. METHODS: 4629 myocardial infarction cases and 5934 controls were compared. Cases were UK men aged 30-54 years and women aged 30-64 years recruited on presentation to hospital with confirmed myocardial infarction. Controls were aged 30-64 years with no history of cardiovascular disease, but were siblings or children of myocardial infarction survivors, or spouses of such relatives. All risk-ratio calculations allow for this relatedness of some of the controls. An updated meta-analysis of previous studies was also conducted. FINDINGS: The ACE DD genotype was found in 1359 (29.4%) of the myocardial infarction cases and in 1637 (27.6%) of the controls (risk ratio 1.10 [95% CI 1.00-1.21]). The association between myocardial infarction and the DD genotype did not seem to be stronger in the subgroup defined as low risk by previously used criteria (234 [28%] of 836 cases and 911 [28%] of 3253 controls: risk ratio 1.04 [95% CI 0.87-1.24]), or in any other subgroup. Nor was the ACE I/D genotype predictive of subsequent survival. INTERPRETATION: This study involved many more cases than any previously reported study of this question, but did not confirm the existence of any substantial association. In an updated meta-analysis of these results with those of previously published studies, the risk ratio for myocardial infarction with the DD genotype seems to lie in the range 1.0 to about 1.1. Although an increase in risk of up to about 10-15% cannot be ruled out, substantially more extreme risks can be. Moreover, there are not especially strong associations in the subgroups previously selected for emphasis. These findings illustrate the need for some studies of candidate genes to involve much larger populations than is customary, without undue emphasis on retrospectively defined subgroups.
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- 2000
10. Zidovudine, didanosine, and zalcitabine in the treatment of HIV infection: meta-analyses of the randomised evidence. HIV Trialists' Collaborative Group
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Abrams, D, Allan, D, Antunes, F, Breckenridge, A, Bruun, J, Cameron, W, Carbon, C, Chalmers, I, Chang, H, Chodakewitz, J, Clendenin, N, Clumeck, N, Collier, A, Collins, G, Cooper, E, Cooper, D, Danner, S, D'Aquila, R, DeGruttola, V, DeMasi, R, Dee, L, Deyton, L, Dixon, D, Farthing, C, Feinberg, J, Fischl, M, Flepp, M, Gartland, M, Gatell, J, Gazzard, B, Goebel, F, Gotzsche, P, Gringeri, A, Hall, D, Hamilton, J, Hammer, S, Hartigan, P, Heath-Chiozzi, M, Henry, K, Hill, A, Hirschel, B, Ioannidis, J, Kahn, J, Katlama, C, Katzenstein, D, Killen, J, King, E, de Loes, SK, Kravcik, S, Lange, J, Leavitt, R, Leonard, J, Maeland, A, Mannucci, P, Mathiesen, L, McDade, H, Meibohn, A, Melander, H, Merigan, T, Mulder, J, Myers, M, Neaton, J, Nessling, M, Perrin, L, Pettinelli, C, Phair, J, Phillips, A, Pinching, A, Poppa, A, Power, L, Reiss, P, Richman, D, Rooney, J, Rousseau, F, Rutherford, G, Salgo, M, Sandstrom, E, Saravolatz, L, Savidge, G, Schnittman, S, Schooley, R, Seligmann, M, Simberkoff, M, Skowron, G, Slade, P, Smith, D, Smith, RP, Soriano, V, Stanley, K, Stingl, G, Stoffels, P, Struthers, L, Tierney, C, Thompson, M, Van der Broeck, R, Van Leeuven, R, Van Weverling, G, Veenstra, J, Vella, S, Volberding, P, Weber, J, Winslow, D, Yeni, P, Yeo, J, Dormont, J, Sande, M, Weller, I, Babiker, A, Collins, R, Darbyshire, J, Duncan, W, Foulkes, M, Hughes, M, Peto, R, Peto, T, Walker, S, and Grp, HIVTC
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BACKGROUND: To assess the effects of zidovudine, didanosine, and zalcitabine on HIV disease progression and survival, we undertook meta-analyses of individual patient data and tabular data from all randomised trials that compared these agents. METHODS: Individual patient data were available for 7722 participants without AIDS in the nine randomised trials of immediate versus deferred zidovudine, and 7700 participants with or without AIDS in the six trials comparing zidovudine plus didanosine, zidovudine plus zalcitabine, or zidovudine alone. The main outcomes were mortality and disease progression (new AIDS-defining event or death before any such event). FINDINGS: In the comparison of immediate versus deferred zidovudine, during a median follow-up of 50 months, 1908 individuals progressed, of whom 1351 died. In the deferred group, 61% started antiretroviral therapy (median time to therapy 28 months, which was zidovudine monotherapy in 94%). During the first year of follow-up, immediate zidovudine halved the rate of disease progression (p
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- 1999
11. Helicobacter pylori screening and gastric cancer
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Danesh, J, Forman, D, Collins, R, and Peto, R
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General Medicine - Published
- 1996
12. ISIS-3 - A RANDOMIZED COMPARISON OF STREPTOKINASE VS TISSUE PLASMINOGEN-ACTIVATOR VS ANISTREPLASE AND OF ASPIRIN PLUS HEPARIN VS ASPIRIN ALONE AMONG 41,299 CASES OF SUSPECTED ACUTE MYOCARDIAL-INFARCTION
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HUNT, D, VARIGOS, J, DIENSTL, F, LECHLEITNER, P, DEBACKER, G, KORNITZER, M, CAIRNS, J, TURPIE, A, FRITZHANSEN, P, SKAGEN, K, KALA, R, HEIKKILA, J, BOISSEL, J, LEIZOROVICZ, A, SCHRODER, R, KOTHE, K, KARATZAS, N, HORGAN, J, OCALLAGHAN, D, TOGNONI, G, FRANZOSI, M, MAGGIONI, A, COHEN, A, KOSTER, R, WHITE, H, MACMAHON, S, KJEKSHUS, J, REIKVAM, A, CEREMUZYNSKI, L, PAOLASSO, E, DIAZ, R, VALENTIN, V, WILHELMSEN, L, LUNDKVIST, L, MOCCETTI, T, MALACRIDA, R, GENONI, M, COLLINS, R, SLEIGHT, P, Peto, R, Parish, S, DOLL, R, ARMITAGE, P, CEDERHOLMWILLIAMS, S, CONWAY, M, DOVE, P, FLATHER, M, MARSHALL, J, YOUNGMAN, L, JULIAN, D, CHAMBERLAIN, D, WARLOW, C, SANDERCOCK, P, FOX, K, HENNEKENS, C, GOLDHABER, S, TIMMIS, G, YUSUF, S, and MEIER, P
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- 1992
13. Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias
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MacMahon, S, Peto, R, Cutler, J, Collins, R, Sorlie, P, Neaton, J, Abbott, R, Godwin, J, Dyer, A, and Stamler, J
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cardiovascular diseases ,circulatory and respiratory physiology - Abstract
The associations of diastolic blood pressure (DBP) with stroke and with coronary heart disease (CHD) were investigated in nine major prospective observational studies: total 420,000 individuals, 843 strokes, and 4856 CHD events, 6-25 (mean 10) years of follow-up. The combined results demonstrate positive, continuous, and apparently independent associations, with no significant heterogeneity of effect among different studies. Within the range of DBP studied (about 70-110 mm Hg), there was no evidence of any "threshold" below which lower levels of DBP were not associated with lower risks of stroke and of CHD. Previous analyses have described the uncorrected associations of DBP measured just at "baseline" with subsequent disease rates. But, because of the diluting effects of random fluctuations in DBP, these substantially underestimate the true associations of the usual DBP (ie, an individual's long-term average DBP) with disease. After correction for this "regression dilution" bias, prolonged differences in usual DBP of 5, 7.5, and 10 mm Hg were respectively associated with at least 34%, 46%, and 56% less stroke and at least 21%, 29%, and 37% less CHD. These associations are about 60% greater than in previous uncorrected analyses. (This regression dilution bias is quite general, so analogous corrections to the relations of cholesterol to CHD or of various other risk factors to CHD or to other diseases would likewise increase their estimated strengths.) The DBP results suggest that for the large majority of individuals, whether conventionally "hypertensive" or "normotensive", a lower blood pressure should eventually confer a lower risk of vascular disease.
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- 1990
14. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials.
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Clarke, M., Collins, R., Darby, S., Davies, C., Elphinstone, P., Evans, V., Godwin, J., Gray, R,, Hicks, C., James, S., MacKinnon, E., McGale, P., McHugh, T., Petro, R., Taylor, C., and Wang, Y.
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BREAST cancer surgery , *RADIOTHERAPY , *CANCER in women , *BREAST cancer , *CANCER-related mortality , *DISEASES in women , *CLINICAL trials , *MEDICAL research - Abstract
Summary Background In early breast cancer, variations in local treatment that substantially affect the risk of locoregional recurrence could also affect long-term breast cancer mortality. To examine this relationship, collaborative meta-analyses were undertaken, based on individual patient data, of the relevant randomised trials that began by 1995. Methods Information was available on 42 000 women in 78 randomised treatment comparisons (radiotherapy vs no radiotherapy, 23 500; more vs less surgery, 9300; more surgery vs radiotherapy, 9300). 24 types of local treatment comparison were identified. To help relate the effect on local (ie, locoregional) recurrence to that on breast cancer mortality, these were grouped according to whether or not the 5-year local recurrence risk exceeded 10% (<10%, 17 000 women; >10%, 25 000 women). Findings About three-quarters of the eventual local recurrence risk occurred during the first 5 years. In the comparisons that involved little (<10%) difference in 5-year local recurrence risk there was little difference in 15-year breast cancer mortality. Among the 25 000 women in the comparisons that involved substantial (>10%) differences, however, 5-year local recurrence risks were 7% active versus 26% control (absolute reduction 19%), and 15-year breast cancer mortality risks were 44·6% versus 49·5% (absolute reduction 5·0%, SE 0·8, 2p<0·00001). These 25 000 women included 7300 with breast-conserving surgery (BCS) in trials of radiotherapy (generally just to the conserved breast), with 5-year local recurrence risks (mainly in the conserved breast, as most had axillary clearance and node-negative disease) 7% versus 26% (reduction 19%), and 15-year breast cancer mortality risks 30·5% versus 35·9% (reduction 5·4%, SE 1·7, 2p=0·0002; overall mortality reduction 5·3%, SE 1·8, 2p=0·005). They also included 8500 with mastectomy, axillary clearance, and node-positive disease in trials of radiotherapy (generally to the chest wall and regional lymph nodes), with similar absolute gains from radiotherapy; 5-year local recurrence risks (mainly at these sites) 6% versus 23% (reduction 17%), and 15-year breast cancer mortality risks 54·7% versus 60·1% (reduction 5·4%, SE 1·3, 2p=0·0002; overall mortality reduction 4·4%, SE 1·2, 2p=0·0009). Radiotherapy produced similar proportional reductions in local recurrence in all women (irrespective of age or tumour characteristics) and in all major trials of radiotherapy versus not (recent or older; with or without systemic therapy), so large absolute reductions in local recurrence were seen only if the control risk was large. INSET: Panel:. [ABSTRACT FROM AUTHOR]
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- 2005
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15. Reliable assessment of the effects of treatment on mortality and major morbidity, II: observational studies.
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MacMahon S and Collins R
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- 2001
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16. Reliable assessment of the effects of treatment on mortality and major morbidity, I: clinical trials.
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Collins R and MacMahon S
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- 2001
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17. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis.
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Kearney PM, Blackwell L, Collins R, Keech A, Simes J, Peto R, Armitage J, Baigent C, Cholesterol Treatment Trialists' (CTT) Collaborators, Kearney, P M, Blackwell, L, Collins, R, Keech, A, Simes, J, Peto, R, Armitage, J, and Baigent, C
- Abstract
Background: Although statin therapy reduces the risk of occlusive vascular events in people with diabetes mellitus, there is uncertainty about the effects on particular outcomes and whether such effects depend on the type of diabetes, lipid profile, or other factors. We undertook a prospective meta-analysis to help resolve these uncertainties.Methods: We analysed data from 18 686 individuals with diabetes (1466 with type 1 and 17,220 with type 2) in the context of a further 71,370 without diabetes in 14 randomised trials of statin therapy. Weighted estimates were obtained of effects on clinical outcomes per 1.0 mmol/L reduction in LDL cholesterol.Findings: During a mean follow-up of 4.3 years, there were 3247 major vascular events in people with diabetes. There was a 9% proportional reduction in all-cause mortality per mmol/L reduction in LDL cholesterol in participants with diabetes (rate ratio [RR] 0.91, 99% CI 0.82-1.01; p=0.02), which was similar to the 13% reduction in those without diabetes (0.87, 0.82-0.92; p<0.0001). This finding reflected a significant reduction in vascular mortality (0.87, 0.76-1.00; p=0.008) and no effect on non-vascular mortality (0.97, 0.82-1.16; p=0.7) in participants with diabetes. There was a significant 21% proportional reduction in major vascular events per mmol/L reduction in LDL cholesterol in people with diabetes (0.79, 0.72-0.86; p<0.0001), which was similar to the effect observed in those without diabetes (0.79, 0.76-0.82; p<0.0001). In diabetic participants there were reductions in myocardial infarction or coronary death (0.78, 0.69-0.87; p<0.0001), coronary revascularisation (0.75, 0.64-0.88; p<0.0001), and stroke (0.79, 0.67-0.93; p=0.0002). Among people with diabetes the proportional effects of statin therapy were similar irrespective of whether there was a prior history of vascular disease and irrespective of other baseline characteristics. After 5 years, 42 (95% CI 30-55) fewer people with diabetes had major vascular events per 1000 allocated statin therapy.Interpretation: Statin therapy should be considered for all diabetic individuals who are at sufficiently high risk of vascular events. [ABSTRACT FROM AUTHOR]- Published
- 2008
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18. High-risk elderly patients PROSPER from cholesterol-lowering therapy.
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Collins R and Armitage J
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- 2002
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19. GISSI-2: 10% reduction in mortality with heparin in acute myocardial infarction?
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Collins, R, Flather, M, and Peto, R
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HEPARIN , *EXPERIMENTAL design , *MYOCARDIAL infarction - Published
- 1990
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20. Immediate versus deferred zidovudine.
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Peto, R and Collins, R
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AIDS-related complex , *AZIDOTHYMIDINE , *CLINICAL trials , *HIV infections , *TIME , *TREATMENT effectiveness - Published
- 1993
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21. Aspirin versus clopidogrel: the wrong question?
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Born, G V R and Collins, R
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- 1997
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22. Tacrolimus (FK506) versus cyclosporin in prevention of liver allograft rejection.
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Collins, R H
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CYCLOSPORINE , *TACROLIMUS , *KIDNEYS , *LIVER transplantation , *NERVOUS system - Published
- 1994
23. Effects on 11-year mortality and morbidity of lowering LDL cholesterol with simvastatin for about 5 years in 20,536 high-risk individuals: a randomised controlled trial.
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Bulbulia R, Bowman L, Wallendszus K, Parish S, Armitage J, Peto R, Collins R, Heart Protection Study Collaborative Group, Bulbulia, R, Bowman, L, Wallendszus, K, Parish, S, Armitage, J, Peto, R, and Collins, R
- Abstract
Background: Findings of large randomised trials have shown that lowering LDL cholesterol with statins reduces vascular morbidity and mortality rapidly, but limited evidence exists about the long-term efficacy and safety of statin treatment. The aim of the extended follow-up of the Heart Protection Study (HPS) is to assess long-term efficacy and safety of lowering LDL cholesterol with statins, and here we report cause-specific mortality and major morbidity in the in-trial and post-trial periods.Methods: 20,536 patients at high risk of vascular and non-vascular outcomes were allocated either 40 mg simvastatin daily or placebo, using minimised randomisation. Mean in-trial follow-up was 5·3 years (SD 1·2), and post-trial follow-up of surviving patients yielded a mean total duration of 11·0 years (SD 0·6). The primary outcome of the long-term follow-up of HPS was first post-randomisation major vascular event, and analysis was by intention to treat. This trial is registered with ISRCTN, number 48489393.Findings: During the in-trial period, allocation to simvastatin yielded an average reduction in LDL cholesterol of 1·0 mmol/L and a proportional decrease in major vascular events of 23% (95% CI 19-28; p<0·0001), with significant divergence each year after the first. During the post-trial period (when statin use and lipid concentrations were similar in both groups), no further significant reductions were noted in either major vascular events (risk ratio [RR] 0·95 [0·89-1·02]) or vascular mortality (0·98 [0·90-1·07]). During the combined in-trial and post-trial periods, no significant differences were recorded in cancer incidence at all sites (0·98 [0·92-1·05]) or any particular site, or in mortality attributed to cancer (1·01 [0·92-1·11]) or to non-vascular causes (0·96 [0·89-1·03]).Interpretation: More prolonged LDL-lowering statin treatment produces larger absolute reductions in vascular events. Moreover, even after study treatment stopped in HPS, benefits persisted for at least 5 years without any evidence of emerging hazards. These findings provide further support for the prompt initiation and long-term continuation of statin treatment.Funding: UK Medical Research Council, British Heart Foundation, Merck & Co, Roche Vitamins. [ABSTRACT FROM AUTHOR]- Published
- 2011
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24. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials.
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Early Breast Cancer Trialists' Collaborative Group, Clarke, M, Collins, R, Darby, S, Davies, C, Elphinstone, P, Evans, V, Godwin, J, Gray, R, Hicks, C, James, S, MacKinnon, E, McGale, P, McHugh, T, Peto, R, Taylor, C, Wang, Y, and Early Breast Cancer Trialists' Collaborative Group (EBCTCG)
- Abstract
Background: In early breast cancer, variations in local treatment that substantially affect the risk of locoregional recurrence could also affect long-term breast cancer mortality. To examine this relationship, collaborative meta-analyses were undertaken, based on individual patient data, of the relevant randomised trials that began by 1995.Methods: Information was available on 42,000 women in 78 randomised treatment comparisons (radiotherapy vs no radiotherapy, 23,500; more vs less surgery, 9300; more surgery vs radiotherapy, 9300). 24 types of local treatment comparison were identified. To help relate the effect on local (ie, locoregional) recurrence to that on breast cancer mortality, these were grouped according to whether or not the 5-year local recurrence risk exceeded 10% (<10%, 17,000 women; >10%, 25,000 women).Findings: About three-quarters of the eventual local recurrence risk occurred during the first 5 years. In the comparisons that involved little (<10%) difference in 5-year local recurrence risk there was little difference in 15-year breast cancer mortality. Among the 25,000 women in the comparisons that involved substantial (>10%) differences, however, 5-year local recurrence risks were 7% active versus 26% control (absolute reduction 19%), and 15-year breast cancer mortality risks were 44.6% versus 49.5% (absolute reduction 5.0%, SE 0.8, 2p<0.00001). These 25,000 women included 7300 with breast-conserving surgery (BCS) in trials of radiotherapy (generally just to the conserved breast), with 5-year local recurrence risks (mainly in the conserved breast, as most had axillary clearance and node-negative disease) 7% versus 26% (reduction 19%), and 15-year breast cancer mortality risks 30.5% versus 35.9% (reduction 5.4%, SE 1.7, 2p=0.0002; overall mortality reduction 5.3%, SE 1.8, 2p=0.005). They also included 8500 with mastectomy, axillary clearance, and node-positive disease in trials of radiotherapy (generally to the chest wall and regional lymph nodes), with similar absolute gains from radiotherapy; 5-year local recurrence risks (mainly at these sites) 6% versus 23% (reduction 17%), and 15-year breast cancer mortality risks 54.7% versus 60.1% (reduction 5.4%, SE 1.3, 2p=0.0002; overall mortality reduction 4.4%, SE 1.2, 2p=0.0009). Radiotherapy produced similar proportional reductions in local recurrence in all women (irrespective of age or tumour characteristics) and in all major trials of radiotherapy versus not (recent or older; with or without systemic therapy), so large absolute reductions in local recurrence were seen only if the control risk was large. To help assess the life-threatening side-effects of radiotherapy, the trials of radiotherapy versus not were combined with those of radiotherapy versus more surgery. There was, at least with some of the older radiotherapy regimens, a significant excess incidence of contralateral breast cancer (rate ratio 1.18, SE 0.06, 2p=0.002) and a significant excess of non-breast-cancer mortality in irradiated women (rate ratio 1.12, SE 0.04, 2p=0.001). Both were slight during the first 5 years, but continued after year 15. The excess mortality was mainly from heart disease (rate ratio 1.27, SE 0.07, 2p=0.0001) and lung cancer (rate ratio 1.78, SE 0.22, 2p=0.0004).Interpretation: In these trials, avoidance of a local recurrence in the conserved breast after BCS and avoidance of a local recurrence elsewhere (eg, the chest wall or regional nodes) after mastectomy were of comparable relevance to 15-year breast cancer mortality. Differences in local treatment that substantially affect local recurrence rates would, in the hypothetical absence of any other causes of death, avoid about one breast cancer death over the next 15 years for every four local recurrences avoided, and should reduce 15-year overall mortality. [ABSTRACT FROM AUTHOR]- Published
- 2005
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25. Unravelling the fetal origins hypothesis: is there really an inverse association between birthweight and subsequent blood pressure?
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Huxley R, Neil A, and Collins R
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- 2002
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26. COMMIT/CCS-2 studies.
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Garton M, Chen Z, Collins R, Peto R, and on behalf of the COMMIT/CCS-2 collaboration
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- 2006
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27. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials.
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Mihaylova, B, Emberson, J, Blackwell, L, Keech, A, Simes, J, Barnes, E H, Voysey, M, Gray, A, Collins, R, Baigent, C, and Cholesterol Treatment Trialists' (CTT) Collaborators
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Background: Statins reduce LDL cholesterol and prevent vascular events, but their net effects in people at low risk of vascular events remain uncertain.Methods: This meta-analysis included individual participant data from 22 trials of statin versus control (n=134,537; mean LDL cholesterol difference 1·08 mmol/L; median follow-up 4·8 years) and five trials of more versus less statin (n=39,612; difference 0·51 mmol/L; 5·1 years). Major vascular events were major coronary events (ie, non-fatal myocardial infarction or coronary death), strokes, or coronary revascularisations. Participants were separated into five categories of baseline 5-year major vascular event risk on control therapy (no statin or low-intensity statin) (<5%, ≥5% to <10%, ≥10% to <20%, ≥20% to <30%, ≥30%); in each, the rate ratio (RR) per 1·0 mmol/L LDL cholesterol reduction was estimated.Findings: Reduction of LDL cholesterol with a statin reduced the risk of major vascular events (RR 0·79, 95% CI 0·77-0·81, per 1·0 mmol/L reduction), largely irrespective of age, sex, baseline LDL cholesterol or previous vascular disease, and of vascular and all-cause mortality. The proportional reduction in major vascular events was at least as big in the two lowest risk categories as in the higher risk categories (RR per 1·0 mmol/L reduction from lowest to highest risk: 0·62 [99% CI 0·47-0·81], 0·69 [99% CI 0·60-0·79], 0·79 [99% CI 0·74-0·85], 0·81 [99% CI 0·77-0·86], and 0·79 [99% CI 0·74-0·84]; trend p=0·04), which reflected significant reductions in these two lowest risk categories in major coronary events (RR 0·57, 99% CI 0·36-0·89, p=0·0012, and 0·61, 99% CI 0·50-0·74, p<0·0001) and in coronary revascularisations (RR 0·52, 99% CI 0·35-0·75, and 0·63, 99% CI 0·51-0·79; both p<0·0001). For stroke, the reduction in risk in participants with 5-year risk of major vascular events lower than 10% (RR per 1·0 mmol/L LDL cholesterol reduction 0·76, 99% CI 0·61-0·95, p=0·0012) was also similar to that seen in higher risk categories (trend p=0·3). In participants without a history of vascular disease, statins reduced the risks of vascular (RR per 1·0 mmol/L LDL cholesterol reduction 0·85, 95% CI 0·77-0·95) and all-cause mortality (RR 0·91, 95% CI 0·85-0·97), and the proportional reductions were similar by baseline risk. There was no evidence that reduction of LDL cholesterol with a statin increased cancer incidence (RR per 1·0 mmol/L LDL cholesterol reduction 1·00, 95% CI 0·96-1·04), cancer mortality (RR 0·99, 95% CI 0·93-1·06), or other non-vascular mortality.Interpretation: In individuals with 5-year risk of major vascular events lower than 10%, each 1 mmol/L reduction in LDL cholesterol produced an absolute reduction in major vascular events of about 11 per 1000 over 5 years. This benefit greatly exceeds any known hazards of statin therapy. Under present guidelines, such individuals would not typically be regarded as suitable for LDL-lowering statin therapy. The present report suggests, therefore, that these guidelines might need to be reconsidered.Funding: British Heart Foundation; UK Medical Research Council; Cancer Research UK; European Community Biomed Programme; Australian National Health and Medical Research Council; National Heart Foundation, Australia. [ABSTRACT FROM AUTHOR]- Published
- 2012
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28. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials.
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Cholesterol Treatment Trialists' (CTT) Collaboration, Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent, C, Blackwell, L, Emberson, J, Holland, L E, Reith, C, Bhala, N, Peto, R, Barnes, E H, Keech, A, Simes, J, and Collins, R
- Abstract
Background: Lowering of LDL cholesterol with standard statin regimens reduces the risk of occlusive vascular events in a wide range of individuals. We aimed to assess the safety and efficacy of more intensive lowering of LDL cholesterol with statin therapy.Methods: We undertook meta-analyses of individual participant data from randomised trials involving at least 1000 participants and at least 2 years' treatment duration of more versus less intensive statin regimens (five trials; 39 612 individuals; median follow-up 5·1 years) and of statin versus control (21 trials; 129 526 individuals; median follow-up 4·8 years). For each type of trial, we calculated not only the average risk reduction, but also the average risk reduction per 1·0 mmol/L LDL cholesterol reduction at 1 year after randomisation.Findings: In the trials of more versus less intensive statin therapy, the weighted mean further reduction in LDL cholesterol at 1 year was 0·51 mmol/L. Compared with less intensive regimens, more intensive regimens produced a highly significant 15% (95% CI 11-18; p<0·0001) further reduction in major vascular events, consisting of separately significant reductions in coronary death or non-fatal myocardial infarction of 13% (95% CI 7-19; p<0·0001), in coronary revascularisation of 19% (95% CI 15-24; p<0·0001), and in ischaemic stroke of 16% (95% CI 5-26; p=0·005). Per 1·0 mmol/L reduction in LDL cholesterol, these further reductions in risk were similar to the proportional reductions in the trials of statin versus control. When both types of trial were combined, similar proportional reductions in major vascular events per 1·0 mmol/L LDL cholesterol reduction were found in all types of patient studied (rate ratio [RR] 0·78, 95% CI 0·76-0·80; p<0·0001), including those with LDL cholesterol lower than 2 mmol/L on the less intensive or control regimen. Across all 26 trials, all-cause mortality was reduced by 10% per 1·0 mmol/L LDL reduction (RR 0·90, 95% CI 0·87-0·93; p<0·0001), largely reflecting significant reductions in deaths due to coronary heart disease (RR 0·80, 99% CI 0·74-0·87; p<0·0001) and other cardiac causes (RR 0·89, 99% CI 0·81-0·98; p=0·002), with no significant effect on deaths due to stroke (RR 0·96, 95% CI 0·84-1·09; p=0·5) or other vascular causes (RR 0·98, 99% CI 0·81-1·18; p=0·8). No significant effects were observed on deaths due to cancer or other non-vascular causes (RR 0·97, 95% CI 0·92-1·03; p=0·3) or on cancer incidence (RR 1·00, 95% CI 0·96-1·04; p=0·9), even at low LDL cholesterol concentrations.Interpretation: Further reductions in LDL cholesterol safely produce definite further reductions in the incidence of heart attack, of revascularisation, and of ischaemic stroke, with each 1·0 mmol/L reduction reducing the annual rate of these major vascular events by just over a fifth. There was no evidence of any threshold within the cholesterol range studied, suggesting that reduction of LDL cholesterol by 2-3 mmol/L would reduce risk by about 40-50%.Funding: UK Medical Research Council, British Heart Foundation, European Community Biomed Programme, Australian National Health and Medical Research Council, and National Heart Foundation. [ABSTRACT FROM AUTHOR]- Published
- 2010
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29. Lipoprotein-associated phospholipase A(2) and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies.
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Thompson A, Gao P, Orfei L, Watson S, Di Angelantonio E, Kaptoge S, Ballantyne C, Cannon CP, Criqui M, Cushman M, Hofman A, Packard C, Thompson SG, Collins R, Danesh J, Lp-PLA(2) Studies Collaboration, Thompson, Alexander, Gao, Pei, Orfei, Lia, and Watson, Sarah
- Abstract
Background: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), an inflammatory enzyme expressed in atherosclerotic plaques, is a therapeutic target being assessed in trials of vascular disease prevention. We investigated associations of circulating Lp-PLA(2) mass and activity with risk of coronary heart disease, stroke, and mortality under different circumstances.Methods: With use of individual records from 79 036 participants in 32 prospective studies (yielding 17 722 incident fatal or non-fatal outcomes during 474 976 person-years at risk), we did a meta-analysis of within-study regressions to calculate risk ratios (RRs) per 1 SD higher value of Lp-PLA(2) or other risk factor. The primary outcome was coronary heart disease.Findings: Lp-PLA(2) activity and mass were associated with each other (r=0.51, 95% CI 0.47-0.56) and proatherogenic lipids. We noted roughly log-linear associations of Lp-PLA(2) activity and mass with risk of coronary heart disease and vascular death. RRs, adjusted for conventional risk factors, were: 1.10 (95% CI 1.05-1.16) with Lp-PLA(2) activity and 1.11 (1.07-1.16) with Lp-PLA(2) mass for coronary heart disease; 1.08 (0.97-1.20) and 1.14 (1.02-1.27) for ischaemic stroke; 1.16 (1.09-1.24) and 1.13 (1.05-1.22) for vascular mortality; and 1.10 (1.04-1.17) and 1.10 (1.03-1.18) for non-vascular mortality, respectively. RRs with Lp-PLA(2) did not differ significantly in people with and without initial stable vascular disease, apart from for vascular death with Lp-PLA(2) mass. Adjusted RRs for coronary heart disease were 1.10 (1.02-1.18) with non-HDL cholesterol and 1.10 (1.00-1.21) with systolic blood pressure.Interpretation: Lp-PLA(2) activity and mass each show continuous associations with risk of coronary heart disease, similar in magnitude to that with non-HDL cholesterol or systolic blood pressure in this population. Associations of Lp-PLA(2) mass and activity are not exclusive to vascular outcomes, and the vascular associations depend at least partly on lipids.Funding: UK Medical Research Council, GlaxoSmithKline, and British Heart Foundation. [ABSTRACT FROM AUTHOR]- Published
- 2010
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30. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis.
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Kaptoge S, Di Angelantonio E, Lowe G, Pepys MB, Thompson SG, Collins R, Danesh J, Emerging Risk Factors Collaboration, Kaptoge, Stephen, Di Angelantonio, Emanuele, Lowe, Gordon, Pepys, Mark B, Thompson, Simon G, Collins, Rory, and Danesh, John
- Abstract
Background: Associations of C-reactive protein (CRP) concentration with risk of major diseases can best be assessed by long-term prospective follow-up of large numbers of people. We assessed the associations of CRP concentration with risk of vascular and non-vascular outcomes under different circumstances.Methods: We meta-analysed individual records of 160 309 people without a history of vascular disease (ie, 1.31 million person-years at risk, 27 769 fatal or non-fatal disease outcomes) from 54 long-term prospective studies. Within-study regression analyses were adjusted for within-person variation in risk factor levels.Results: Log(e) CRP concentration was linearly associated with several conventional risk factors and inflammatory markers, and nearly log-linearly with the risk of ischaemic vascular disease and non-vascular mortality. Risk ratios (RRs) for coronary heart disease per 1-SD higher log(e) CRP concentration (three-fold higher) were 1.63 (95% CI 1.51-1.76) when initially adjusted for age and sex only, and 1.37 (1.27-1.48) when adjusted further for conventional risk factors; 1.44 (1.32-1.57) and 1.27 (1.15-1.40) for ischaemic stroke; 1.71 (1.53-1.91) and 1.55 (1.37-1.76) for vascular mortality; and 1.55 (1.41-1.69) and 1.54 (1.40-1.68) for non-vascular mortality. RRs were largely unchanged after exclusion of smokers or initial follow-up. After further adjustment for fibrinogen, the corresponding RRs were 1.23 (1.07-1.42) for coronary heart disease; 1.32 (1.18-1.49) for ischaemic stroke; 1.34 (1.18-1.52) for vascular mortality; and 1.34 (1.20-1.50) for non-vascular mortality.Interpretation: CRP concentration has continuous associations with the risk of coronary heart disease, ischaemic stroke, vascular mortality, and death from several cancers and lung disease that are each of broadly similar size. The relevance of CRP to such a range of disorders is unclear. Associations with ischaemic vascular disease depend considerably on conventional risk factors and other markers of inflammation.Funding: British Heart Foundation, UK Medical Research Council, BUPA Foundation, and GlaxoSmithKline. [ABSTRACT FROM AUTHOR]- Published
- 2010
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31. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths.
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Lewington S, Whitlock G, Clarke R, Sherliker P, Emberson J, Halsey J, Qizilbash N, Peto R, Collins R, Prospective Studies Collaboration, Lewington, Sarah, Whitlock, Gary, Clarke, Robert, Sherliker, Paul, Emberson, Jonathan, Halsey, Jim, Qizilbash, Nawab, Peto, Richard, and Collins, Rory
- Abstract
Background: Age, sex, and blood pressure could modify the associations of total cholesterol (and its main two fractions, HDL and LDL cholesterol) with vascular mortality. This meta-analysis combined prospective studies of vascular mortality that recorded both blood pressure and total cholesterol at baseline, to determine the joint relevance of these two risk factors.Methods: Information was obtained from 61 prospective observational studies, mostly in western Europe or North America, consisting of almost 900,000 adults without previous disease and with baseline measurements of total cholesterol and blood pressure. During nearly 12 million person years at risk between the ages of 40 and 89 years, there were more than 55,000 vascular deaths (34,000 ischaemic heart disease [IHD], 12,000 stroke, 10,000 other). Information about HDL cholesterol was available for 150,000 participants, among whom there were 5000 vascular deaths (3000 IHD, 1000 stroke, 1000 other). Reported associations are with usual cholesterol levels (ie, corrected for the regression dilution bias).Findings: 1 mmol/L lower total cholesterol was associated with about a half (hazard ratio 0.44 [95% CI 0.42-0.48]), a third (0.66 [0.65-0.68]), and a sixth (0.83 [0.81-0.85]) lower IHD mortality in both sexes at ages 40-49, 50-69, and 70-89 years, respectively, throughout the main range of cholesterol in most developed countries, with no apparent threshold. The proportional risk reduction decreased with increasing blood pressure, since the absolute effects of cholesterol and blood pressure were approximately additive. Of various simple indices involving HDL cholesterol, the ratio total/HDL cholesterol was the strongest predictor of IHD mortality (40% more informative than non-HDL cholesterol and more than twice as informative as total cholesterol). Total cholesterol was weakly positively related to ischaemic and total stroke mortality in early middle age (40-59 years), but this finding could be largely or wholly accounted for by the association of cholesterol with blood pressure. Moreover, a positive relation was seen only in middle age and only in those with below-average blood pressure; at older ages (70-89 years) and, particularly, for those with systolic blood pressure over about 145 mm Hg, total cholesterol was negatively related to haemorrhagic and total stroke mortality. The results for other vascular mortality were intermediate between those for IHD and stroke.Interpretation: Total cholesterol was positively associated with IHD mortality in both middle and old age and at all blood pressure levels. The absence of an independent positive association of cholesterol with stroke mortality, especially at older ages or higher blood pressures, is unexplained, and invites further research. Nevertheless, there is conclusive evidence from randomised trials that statins substantially reduce not only coronary event rates but also total stroke rates in patients with a wide range of ages and blood pressures. [ABSTRACT FROM AUTHOR]- Published
- 2007
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32. Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66,155 cases and 91,307 controls.
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Ye Z, Liu EHC, Higgins JPT, Keavney BD, Lowe GDO, Collins R, and Danesh J
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- 2006
33. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.
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Cholesterol Treatment Trialists' Collaborators, Baigent, C, Keech, A, Kearney, P M, Blackwell, L, Buck, G, Pollicino, C, Kirby, A, Sourjina, T, Peto, R, Collins, R, Simes, R, and Cholesterol Treatment Trialists' (CTT) Collaborators
- Abstract
Background: Results of previous randomised trials have shown that interventions that lower LDL cholesterol concentrations can significantly reduce the incidence of coronary heart disease (CHD) and other major vascular events in a wide range of individuals. But each separate trial has limited power to assess particular outcomes or particular categories of participant.Methods: A prospective meta-analysis of data from 90,056 individuals in 14 randomised trials of statins was done. Weighted estimates were obtained of effects on different clinical outcomes per 1.0 mmol/L reduction in LDL cholesterol.Findings: During a mean of 5 years, there were 8186 deaths, 14,348 individuals had major vascular events, and 5103 developed cancer. Mean LDL cholesterol differences at 1 year ranged from 0.35 mmol/L to 1.77 mmol/L (mean 1.09) in these trials. There was a 12% proportional reduction in all-cause mortality per mmol/L reduction in LDL cholesterol (rate ratio [RR] 0.88, 95% CI 0.84-0.91; p<0.0001). This reflected a 19% reduction in coronary mortality (0.81, 0.76-0.85; p<0.0001), and non-significant reductions in non-coronary vascular mortality (0.93, 0.83-1.03; p=0.2) and non-vascular mortality (0.95, 0.90-1.01; p=0.1). There were corresponding reductions in myocardial infarction or coronary death (0.77, 0.74-0.80; p<0.0001), in the need for coronary revascularisation (0.76, 0.73-0.80; p<0.0001), in fatal or non-fatal stroke (0.83, 0.78-0.88; p<0.0001), and, combining these, of 21% in any such major vascular event (0.79, 0.77-0.81; p<0.0001). The proportional reduction in major vascular events differed significantly (p<0.0001) according to the absolute reduction in LDL cholesterol achieved, but not otherwise. These benefits were significant within the first year, but were greater in subsequent years. Taking all years together, the overall reduction of about one fifth per mmol/L LDL cholesterol reduction translated into 48 (95% CI 39-57) fewer participants having major vascular events per 1000 among those with pre-existing CHD at baseline, compared with 25 (19-31) per 1000 among participants with no such history. There was no evidence that statins increased the incidence of cancer overall (1.00, 0.95-1.06; p=0.9) or at any particular site.Interpretation: Statin therapy can safely reduce the 5-year incidence of major coronary events, coronary revascularisation, and stroke by about one fifth per mmol/L reduction in LDL cholesterol, largely irrespective of the initial lipid profile or other presenting characteristics. The absolute benefit relates chiefly to an individual's absolute risk of such events and to the absolute reduction in LDL cholesterol achieved. These findings reinforce the need to consider prolonged statin treatment with substantial LDL cholesterol reductions in all patients at high risk of any type of major vascular event. [ABSTRACT FROM AUTHOR]- Published
- 2005
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34. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial.
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Dahlöf B, Sever PS, Poulter NR, Wedel H, Beevers DG, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Östergren J, ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) Investigators, Dahlöf, Björn, Sever, Peter S, Poulter, Neil R, Wedel, Hans, and Beevers, D Gareth
- Abstract
Background: The apparent shortfall in prevention of coronary heart disease (CHD) noted in early hypertension trials has been attributed to disadvantages of the diuretics and beta blockers used. For a given reduction in blood pressure, some suggested that newer agents would confer advantages over diuretics and beta blockers. Our aim, therefore, was to compare the effect on non-fatal myocardial infarction and fatal CHD of combinations of atenolol with a thiazide versus amlodipine with perindopril.Methods: We did a multicentre, prospective, randomised controlled trial in 19 257 patients with hypertension who were aged 40-79 years and had at least three other cardiovascular risk factors. Patients were assigned either amlodipine 5-10 mg adding perindopril 4-8 mg as required (amlodipine-based regimen; n=9639) or atenolol 50-100 mg adding bendroflumethiazide 1.25-2.5 mg and potassium as required (atenolol-based regimen; n=9618). Our primary endpoint was non-fatal myocardial infarction (including silent myocardial infarction) and fatal CHD. Analysis was by intention to treat.Findings: The study was stopped prematurely after 5.5 years' median follow-up and accumulated in total 106 153 patient-years of observation. Though not significant, compared with the atenolol-based regimen, fewer individuals on the amlodipine-based regimen had a primary endpoint (429 vs 474; unadjusted HR 0.90, 95% CI 0.79-1.02, p=0.1052), fatal and non-fatal stroke (327 vs 422; 0.77, 0.66-0.89, p=0.0003), total cardiovascular events and procedures (1362 vs 1602; 0.84, 0.78-0.90, p<0.0001), and all-cause mortality (738 vs 820; 0.89, 0.81-0.99, p=0.025). The incidence of developing diabetes was less on the amlodipine-based regimen (567 vs 799; 0.70, 0.63-0.78, p<0.0001).Interpretation: The amlodipine-based regimen prevented more major cardiovascular events and induced less diabetes than the atenolol-based regimen. On the basis of previous trial evidence, these effects might not be entirely explained by better control of blood pressure, and this issue is addressed in the accompanying article. Nevertheless, the results have implications with respect to optimum combinations of antihypertensive agents. [ABSTRACT FROM AUTHOR]- Published
- 2005
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35. Four paraoxonase gene polymorphisms in 11 212 cases of coronary heart disease and 12 786 controls: meta-analysis of 43 studies.
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Wheeler JG, Keavaney BD, Watkins H, Collins R, and Danesh J
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- 2004
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36. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial -- Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial.
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Sever PS, Dahlöf B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Östergren J, and ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) Investigators
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- 2003
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37. Unravelling the fetal origins hypothesis.
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Eriksson JG, Forsén T, Hennessy E, Holemans K, Caluwaerts S, Van Assche FA, Cruickshank JK, Beith C, Koudsi A, Huxley R, Neil A, and Collins R
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- 2002
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38. MRC/BHF Heart Protection Study.
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Robins SJ, Despres J, Vaughan CJ, Buckley BM, Wald N, Law M, Durrington PN, Bates CJ, Brown MJ, Violi F, Micheletta F, Iuliano L, Collins R, Armitage J, Parish S, Sleight P, Peto R, Vaughan, Carl J, Buckley, Brendan M, and MRC/BHF Heart Protection Study
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- 2002
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39. Effects of long-term treatment with angiotensin-converting-enzyme inhibitors in the presence or absence of aspirin: a systematic review.
- Author
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Teo KK, Yusuf S, Pfeffer M, Kober L, Hall A, Pogue J, Latini R, Collins R, Angiotensin-Converting-Enzyme Inhibitors Collaborative Group, Teo, Koon K, Yusuf, Salim, Pfeffer, Marc, Torp-Pedersen, Christian, Kober, Lars, Hall, Alistair, Pogue, Janice, Latini, Roberto, Collins, Rory, and ACE Inhibitors Collaborative Group
- Abstract
Background: Results from a retrospective analysis of the Studies of Left Ventricular Dysfunction (SOLVD) study suggest that angiotensin-converting-enzyme (ACE) inhibitors may be less effective in patients receiving aspirin. We aimed to confirm or refute this theory.Methods: We used the Peto-Yusuf method to undertake a systematic overview of data for 22060 patients from six long-term randomised trials of ACE inhibitors to assess whether aspirin altered the effects of ACE inhibitor therapy on major clinical outcomes (composite of death, myocardial infarction, stroke, hospital admission for congestive heart failure, or revascularisation).Findings: Baseline characteristics, and prognosis in patients allocated placebo, differed strikingly between those who were and were not taking aspirin at baseline. Results from analyses of all trials, except SOLVD, did not suggest any significant differences between the proportional reductions in risk with ACE inhibitor therapy in the presence or absence of aspirin for the major clinical outcomes (p=0.15), or in any of its individual components, except myocardial infarction (interaction p=0.01). Overall, ACE inhibitor therapy significantly reduced the risk of the major clinical outcomes by 22% (p<0.0001), with clear reductions in risk both among those receiving aspirin at baseline (odds ratio 0.80, [99% CI 0.73-0.88]) and those who were not (0.71 [99% CI 0.62-0.81], interaction p=0.07).Interpretation: Considering the totality of evidence on all major vascular outcomes in these trials, there is only weak evidence of any reduction in the benefit of ACE-inhibitor therapy when added to aspirin. However, there is definite evidence of clinically important benefits with respect to these major clinical outcomes with ACE-inhibitor therapy, irrespective of whether concomitant aspirin is used. [ABSTRACT FROM AUTHOR]- Published
- 2002
40. Clopidogrel and metoprolol in myocardial infarction.
- Author
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Borja J, García O, Donado E, Izquierdo I, Karthikeyan G, Bhala N, Taggar J, Chen Z, Collins R, Peto R, Xie J, Jiang L, and Liu L
- Published
- 2006
- Full Text
- View/download PDF
41. Efficacy and safety of cholesterol-lowering treatment.
- Author
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Abraha I, Bonacini I, Montedori A, Law M, Wald NJ, Baigent C, Keech A, Kearney P, Collins R, Simes J, Farrar K, Bundred P, Richards N, Armstrong D, and Cholesterol Treatment Trialists' Collaboration
- Published
- 2006
- Full Text
- View/download PDF
42. Comments on the MRC/BHF Heart Protection Study.
- Author
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Pechlaner C, Mikhail N, Sirtori CR, Collins R, Armitage J, Parish S, Sleight P, Peto R, and Abramson J
- Published
- 2003
- Full Text
- View/download PDF
43. Paraoxonase polymorphisms and coronary heart disease.
- Author
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Durrington PN, Mackness B, Mackness MI, Wheeler J, Keavney B, Watkins H, Collins R, and Danesh J
- Published
- 2004
- Full Text
- View/download PDF
44. New analyses of Heart Protection Study.
- Author
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Lemiengre M, van Driel M, Chevalier P, De Meyere M, Christiaens T, Collins R, Armitage J, Parish S, Sleight P, and Peto R
- Published
- 2004
- Full Text
- View/download PDF
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