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Lancet. 2008 Apr 26;371(9622):1417-26. doi: 10.1016/S0140-6736(08)60423-7. Epub 2008 Apr 2.

Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration.

Collaborators (578)

Collins S, Dabis F, D'Arminio Monforte A, De Wit S, El-Sadr WM, Kirk O, Law M, Pradier C, Phillips A, Reiss P, Rosseau F, Storfer SP, Weber I, Lundgren JD, Worm SW, Friis-Møller N, Sabin CA, Sjøl A, Lundgren JD, Sawitz A, Rickenbach M, Pezzotti P, Krum E, Gras L, Balestre E, Sundström A, Poll B, Fontas E, Torres F, Petoumenos K, Kjaer J, Hammer S, Neaton J, Sjøl A, de Wolf F, Zaheri S, Gras L, Bronsveld W, Hillebrand-Haverkort ME, Prins JM, Bos JC, Eeftinck Schattenkerk JK, Geerlings SE, Godfried MH, Lange JM, van Leth FC, Lowe SH, van der Meer JT, Nellen FJ, Pogány K, van der Poll T, Reiss P, Ruys TA, Sankatsing, Steingrover R, van Twillert G, van der Valk M, van Vonderen MG, Vrouenraets SM, van Vugt M, Wit FW, van Eeden A, ten Veen JH, van Dam PS, Roos JC, Brinkman K, Frissen PH, Weigel HM, Mulder JW, van Gorp EC, Meenhorst PL, Mairuhu AT, Veenstra J, Danner SA, Van Agtmael MA, Claessen FA, Perenboom RM, Rijkeboer A, van Vonderen M, Richter C, van der Berg J, van Leusen R, Vriesendorp R, Jeurissen FJ, Kauffmann RH, Koger EL, Bravenboer B, ten Napel CH, Kootstra GJ, Sprenger HG, Miesen WM, Doedens R, Scholvinck EH, ten Kate RW, van Houte DP, Polee M, Kroon FP, van den Broek, van Dissel JT, Schippers EF, Schreij G, van de Geest S, Verbon A, Koopmans PP, Keuter M, Post F, van der Ven AJ, van der Ende ME, Gyssens IC, van der Feltz M, den Hollander JG, de Marie S, Nouwen JL, Rijnders BJ, de Vries TE, Juttmann JR, van de Heul C, van Kasteren ME, St Elisabeth, Schneider MM, Bonten MJ, Borleffs JC, Ellerbroek PM, Hoepelman IM, Jaspers CA, Schouten I, Schurink CA, Blok WL, Tanis AA, Groeneveld PH, Salamon R, Beylot J, Dupon M, Le Bras M, Pellegrin JL, Ragnaud JM, Dabis F, Chêne G, Jacqmin-Gadda H, Thiébaut R, Lawson-Ayayi S, Lavignolle V, Balestre E, Blaizeau MJ, Decoin M, Formaggio AM, Delveaux S, Labarerre S, Uwamaliya B, Vimard E, Merchadou L, Palmer G, Touchard D, Dutoit D, Pereira F, Boulant B, Beylot J, Morlat P, Bernard N, Bonarek M, Bonnet F, Coadou B, Gelie P, Jaubert D, Nouts C, Lacoste D, Dupon M, Dutronc H, Cipriano G, Lafarie S, Chossat I, Lacut JY, Leng B, Pellegrin JL, Mercié P, Viallard JF, Faure I, Rispal P, Cipriano C, Tchamgoué S, Le Bras M, Djossou F, Malvy D, Pivetaud JP, Ragnaud JM, Chambon D, De La Taille C, Galperine T, Lafarie S, Neau D, Ochoa A, Beylot C, Doutre MS, Bezian JH, Moreau JF, Taupin JL, Conri C, Constans J, Couzigou P, Castera L, Fleury H, Lafon ME, Masquelier B, Pellegrin I, Trimoulet P, Moreau F, Mestre C, Series C, Taytard A, Law M, Petoumenos K, Anderson J, Cortossis P, Hoy J, Watson K, Roth N, Bloch M, Franic T, Baker D, McFarlane R, Carr A, Cooper D, Chuah J, Fankhauser W, Mallal S, Forsdyke C, Calvo G, Torres F, Mateu S, Domingo P, Sambeat MA, Gatel J, Del Cacho E, Cadafalch J, Fuster M, Codina C, Sirera G, Vaqué A, Clumeck N, De Wit S, Gerard M, Kabeya K, Konopnicki D, Libois A, Payen MC, Poll B, Van Laethem Y, Neaton J, Bartsch G, El-Sadr WM, Krum E, Thompson G, Wentworth D, Luskin-Hawk R, Telzak E, El-Sadr WM, Abrams DI, Cohn D, Markowitz N, Arduino R, Mushatt D, Friedland G, Perez G, Tedaldi E, Fisher E, Gordin F, Crane LR, Sampson J, Baxter J, Kirk O, Mocroft A, Phillips AN, Lundgren JD, Vetter N, Karpov I, Vassilenko A, Clumeck N, De Wit S, Poll B, Colebunders R, Machala L, Rozsypal H, Sedlacek D, Nielsen J, Benfield T, Gerstoft J, Katzenstein T, Hansen AB, Skinhøj P, Pedersen C, Zilmer K, Katlama C, Viard JP, Girard PM, Saint-Marc T, Vanhems P, Pradier C, Dabis F, Dietrich M, Manegold C, van Lunzen J, Stellbrink HJ, Staszewski S, Bieckel M, Goebel FD, Fätkenheuer G, Rockstroh J, Schmidt RE, Kosmidis J, Gargalianos P, Sambatakou H, Perdios J, Panos G, Filandras A, Banhegyi D, Mulcahy F, Yust I, Burke M, Turner D, Pollack S, Hassoun J, Sthoeger Z, Maayan S, Vella S, Chiesi A, Arici C, Pristerá R, Mazzotta F, Gabbuti A, Esposito R, Bedini A, Chirianni A, Montesarchio E, Vullo V, Santopadre P, Narciso P, Antinori A, Franci P, Zaccarelli M, Lazzarin A, Castagna A, D'Arminio Monforte A, Viksna L, Chaplinskas S, Hemmer R, Staub T, Reiss P, Bruun J, Maeland A, Ormaasen V, Knysz B, Gasiorowski J, Horban A, Prokopowicz D, Wiercinska-Drapalo A, Boron-Kaczmarsk A, Pynka M, Beniowski M, Mularska E, Trocha H, Antunes A, Mansinho K, Maltez F, Duiculescu D, Streinu-Cercel A, Vinogradova E, Rakhmanova A, Jevtovic D, Mokrás M, Staneková D, González-Lahoz J, Sanchez-Conde M, García-Benayas T, Martin-Carbonero L, Soriano V, Clotet B, Jou A, Conejero J, Ruiz L, Tural C, Gatell JM, Miró JM, Zamora L, Domingo P, Gutierrez M, Mateo G, Sambeat MA, Blaxhult A, Karlsson A, Pehrson P, Ledergerber B, Weber R, Francioli P, Telenti A, Hirschel B, Soravia-Dunand V, Furrer H, Kravchenko E, Chentsova N, Fisher M, Brettle R, Barton S, Johnson AM, Mercey D, Murphy M, Johnson MA, Weber J, Scullard G, Morfeld L, Thulin G, Sundström A, Akerlund B, Koppel K, Karlsson A, Flamholc L, Håkangård C, d'Arminio Monforte A, Pezzotti P, Moroni M, d'Arminio Monforte A, Cargnel A, Merli S, Vigevani GM, Pastecchia C, Lazzarin A, Morsica G, Caggese L, Moioli C, Mura MS, Mannazzu M, Suter F, Arici C, Manconi PE, Piano P, Mazzotta F, Lo Caputo S, Poggio A, Bottari G, Pagano G, Alessandrini A, Scasso A, Abbadessa V, Mancuso S, Alberici F, Ruggieri A, Arlotti M, Ortolani P, De Lalla F, Tositti G, Cassola G, Piscopo R, Raise E, Ebo F, Soscia F, Tacconi L, Tirelli U, Cinelli R, Santoro D, Pusterla L, Carosi G, Torti C, Cadeo G, Bertelli D, Carnevale G, Citterio P, Filice G, Bruno R, Di Perri G, Arnaudo I, Caramello P, Orofino GC, Soranzo ML, Bonasso M, Rizzardini G, Melzi S, Chiodo F, Colangeli V, Magnani G, Ursitti M, Menichetti F, Martinelli C, Esposito R, Mussini C, Ghinelli F, Sighinolfi L, Coronado O, Ballardini G, Rizzo E, Montroni M, Braschi MC, Petrelli E, Cioppi A, Cauda R, De Luca A, Petrosillo N, Noto P, Narciso P, Bontempo G, Antinori A, Acinapura R, Antonucci G, De Longis P, Vullo V, Lichtner M, Pastore G, Ladisa N, Chirianni A, Viglietti R, Piazza M, Nappa S, Abrescia N, De Marco M, Colomba A, Prestileo T, De Stefano C, La Gala A, Cosco L, Scerbo A, Grima P, Tundo P, Vecchiet J, D'Alessandro M, Grisorio B, Ferrara S, Pradier C, Fontas E, Caissotti C, Dellamonica P, Bentz L, Bernard E, De Salvador-Guillouet F, Durant J, Mondain-Miton V, Perbost I, Prouvost-Keller B, Pugliese P, Rahelinirina V, Roger PM, Vander F, Battegay M, Bernasconi E, Böni J, Buche H, Bürgisser P, Cattacin S, Cavassini M, Dubs R, Egger M, Elzi L, Erb P, Fischer M, Flepp M, Fontana A, Francioli P, Furrer HJ, Gorgievski M, Günthard H, Hirschel B, Kaiser L, Kind C, Klimkait T, Lauper U, Ledergerber B, Opravil M, Paccaud F, Pantaleo G, Perrin L, Piffaretti JC, Rickenbach M, Rudin C, Schmid P, Schüpbach J, Speck R, Telenti A, Trkola A, Vernazza P, Weber R, Yerly S.

Erratum in

  • Lancet. 2008 Jul 26;372(9635):292.

Abstract

BACKGROUND:

Whether nucleoside reverse transcriptase inhibitors increase the risk of myocardial infarction in HIV-infected individuals is unclear. Our aim was to explore whether exposure to such drugs was associated with an excess risk of myocardial infarction in a large, prospective observational cohort of HIV-infected patients.

METHODS:

We used Poisson regression models to quantify the relation between cumulative, recent (currently or within the preceding 6 months), and past use of zidovudine, didanosine, stavudine, lamivudine, and abacavir and development of myocardial infarction in 33 347 patients enrolled in the D:A:D study. We adjusted for cardiovascular risk factors that are unlikely to be affected by antiretroviral therapy, cohort, calendar year, and use of other antiretrovirals.

FINDINGS:

Over 157,912 person-years, 517 patients had a myocardial infarction. We found no associations between the rate of myocardial infarction and cumulative or recent use of zidovudine, stavudine, or lamivudine. By contrast, recent-but not cumulative-use of abacavir or didanosine was associated with an increased rate of myocardial infarction (compared with those with no recent use of the drugs, relative rate 1.90, 95% CI 1.47-2.45 [p=0.0001] with abacavir and 1.49, 1.14-1.95 [p=0.003] with didanosine); rates were not significantly increased in those who stopped these drugs more than 6 months previously compared with those who had never received these drugs. After adjustment for predicted 10-year risk of coronary heart disease, recent use of both didanosine and abacavir remained associated with increased rates of myocardial infarction (1.49, 1.14-1.95 [p=0.004] with didanosine; 1.89, 1.47-2.45 [p=0.0001] with abacavir).

INTERPRETATION:

There exists an increased risk of myocardial infarction in patients exposed to abacavir and didanosine within the preceding 6 months. The excess risk does not seem to be explained by underlying established cardiovascular risk factors and was not present beyond 6 months after drug cessation.

Comment in

PMID:
18387667
[PubMed - indexed for MEDLINE]
PMCID:
PMC2688660
Free PMC Article
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