Combination Antiretroviral Therapy and the Risk of Myocardial Infarction: The Data Collection on Adverse Events of Anti-HIV Drugs (DAD) Study Group

Nina Friis-Møller, Caroline A. Sabin, Rainer Weber, Antonella d'Arminio Monforte, Wafaa M. El-Sadr, Peter Reiss, Rodolphe Thiébaut, Linda Morfeldt, Stephane De Wit, Christian Pradier, Gonzalo Calvo, Matthew G. Law, Ole Kirk, Andrew N. Phillips, Jens D. Lundgren, G. Bartsch, F. Dabis, F. Houyez, E. Loeliger, R. TresslerI. Weller, A. Sjøl, A. Sawitz, M. Rickenbach, P. Pezzotti, E. Krum, R. Meester, V. Lavignolle, A. Sundström, B. Poll, E. Fontas, F. Torres, K. Petoumenos, J. Kjær, S. Hammer, J. Neaton, A. Sjøl., F. de Wolf, E. van der Ven, S. Zaheri, I. Van Valkengoed, W. Bronsveld, H. Weigel, K. Brinkman, P. Frissen, J. ten Veen, M. Hillebrand, P. van Dam, S. Schieveld, J. Mulder, E. van Gorp, P. Meenhorst, A. van Eeden, S. Danner, F. Claessen, R. Perenboom, J. K. Eeftinck Schattenkerk, M. Godfried, J. Lange, S. Lowe, J. van der Meer, F. Nellen, K. Pogany, T. van der Poll, J. Prins, T. Ruys, M. van der Valk, F. Wit, C. Richter, R. van Leusen, R. Vriesendorp, F. Jeurissen, R. Kauffmann, E. Koger, B. Bravenboer, C. ten Napel, H. G. Sprenger, G. Law, R. W. ten Kate, M. Leemhuis, F. Kroon, E. Schippers, G. Schrey, S. van der Geest, A. Verbon, P. Koopmans, M. Keuter, D. Telgt, A. van der Ven, M. van der Ende, I. Gyssens, S. de Marie, J. Juttmann, C. van der Heul, M. Schneider, J. Borleffs, I. Hoepelman, C. Jaspers, A. Matute, C. Schurink, W. Blok, R. Salamon, J. Beylot, M. Dupon, M. Le Bras, J. L. Pellegrin, J. M. Ragnaud, G. Chêne, H. Jacqmin-Gadda, R. Rhiébaut, S. Lawson-Ayayi, E. Balestre, M. J. Blaizeau, M. Decoin, A. M. Formaggio, S. Delveaux, S. Labarerre, B. Uwamaliya, E. Vimard, L. Merchadou, G. Palmer, D. Touchard, D. Dutoit, F. Pereira, B. Boulant, P. Morlat, N. Bernard, M. Bonarek, F. Bonnet, B. Coadou, P. Gelie, D. Jaubert, C. Nouts, D. Lacoste, H. Dutronc, G. Cipriano, S. Lafarie, I. Chossat, J. Y. Lacut, B. Leng, P. Mercié, J. F. Viallard, I. Faure, P. Rispal, C. Cipriano, S. Tchamgoué, F. Djossou, D. Malvy, J. P. Pivetaud, D. Chambon, C. De La Taille, T. Galperine, D. Neau, A. Ochoa, C. Beylot, M. S. Doutre, J. H. Bezian, J. F. Moreau, J. L. Taupin, C. Conri, J. Constans, P. Couzigou, L. Castera, H. Fleury, M. E. Lafon, B. Masquelier, I. Pellegrin, P. Trimoulet, F. Moreau, C. Mestre, C. Series, A. Taytard, M. Law, J. Anderson, J. Bal, A. Mijch, K. Watson, N. Roth, H. Wood, D. Austin, A. Gowers, D. Baker, R. McFarlane, A. Carr, D. Cooper, J. Chuah, W. Fankhauser, S. Mallal, J. Skett, S. Mateau, P. Domingo, M. A. Sambeat, J. Gatell, E. Del Cacho, J. Cadafalch, M. Fuster, C. Codina, G. Sirera, A. Vaqué, N. Clumeck, M. Gerard, M. Hildebrand, K. Kabeya, D. Konopnicki, M. C. Payen, Y. Van Laethem, G. Thompson, D. Wentworth, R. Luskin-Hawk, E. Telzak, D. I. Abrams, D. Cohn, N. Markowitz, R. Arduino, D. Mushatt, G. Friedland, G. Perez, E. Tedaldi, E. Fisher, F. Gordin, L. R. Crane, J. Sampson, J. Baxter, A. Mocroft, N. Vetter, P. Hermans, R. Colebunders, L. Machala, J. Nielsen, T. Benfield, J. Gerstoft, T. Katzenstein, B. Røge, P. Skinhøj, C. Pedersen, C. Katlama, J. P. Viard, T. Saint-Marc, P. Vanhems, M. Dietrich, C. Manegold, J. van Lunzen, V. Miller, S. Staszewski, M. Bieckel, F. D. Goebel, B. Salzberger, J. Rockstroh, J. Kosmidis, P. Gargalianos, H. Sambatakou, J. Perdios, G. Panos, I. Karydis, A. Filandras, D. Banhegyi, F. Mulcahy, I. Yust, D. Turner, S. Pollack, Z. Ben-Ishai, Z. Bentwich, S. Maayan, S. Vella, A. Chiesi, C. Arici, R. Pristerá, F. Mazzotta, A. Gabbuti, R. Esposito, A. Bedini, A. Chirianni, E. Montesarchio, V. Vullo, P. Santopadre, P. Narciso, A. Antinori, P. Franci, M. Zaccarelli, A. Lazzarin, R. Finazzi, R. Hemmer, T. Staub, J. Bruun, A. Maeland, V. Ormaasen, B. Knysz, J. Gasiorowski, A. Horban, D. Prokopowicz, A. Boron-Kaczmarska, M. Pynka, M. Beniowski, H. Trocha, F. Antunes, K. Mansinho, R. Proenca, J. González-Lahoz, B. Diaz, T. García-Benayas, L. Martin-Carbonero, V. Soriano, B. Clotet, A. Jou, J. Conejero, C. Tural, J. M. Gatell, J. M. Miró, A. Blaxhult, B. Heidemann, P. Pehrson, B. Ledergerber, P. Francioli, A. Telenti, B. Hirschel, V. Soravia-Dunand, H. Furrer, M. Fisher, R. Brettle, S. Barton, A. M. Johnson, D. Mercey, C. Loveday, M. A. Johnson, A. Pinching, J. Parkin, J. Weber, G. Scullard, G. Thulin, B. Åkerlund, K. Koppel, A. Karlsson, L. Flamholc, C. Håkangård, M. Moroni, A. Cargnel, S. Merli, G. M. Vigevani, C. Pastecchia, R. Novati, L. Caggese, C. Moioli, M. S. Mura, M. Mannazzu, F. Suter, P. E. Manconi, P. Piano, S. Lo Caputo, A. Poggio, G. Bottari, G. Pagano, A. Alessandrini, A. Scasso, A. Vincenti, V. Abbadesse, S. Mancuso, F. Alberici, A. Ruggieri, M. Arlotti, P. Ortolani, F. De Lalla, G. Tositti, N. Piersantelli, R. Piscopo, E. Raise, S. Pasquinucci, F. Soscia, L. Tacconi, U. Tirelli, G. Nasti, D. Santoro, L. Pusterla, G. Carosi, F. Castelli, G. Cadeo, D. Vangi, G. Carnevale, D. Galloni, G. Filice, R. Bruno, A. Sinicco, M. Sciandra, P. Caramello, L. Gennero, M. L. Soranzo, M. Bonasso, G. Rizzardini, G. Migliorino, F. Chiodo, V. Colangeli, G. Magnani, M. Ursitti, F. Menichetti, C. Martinelli, C. Mussini, F. Ghinelli, L. Sighinolfi, O. Coronado, T. Zauli, G. Ballardini, M. Montroni, A. Zoli, E. Petrelli, A. Cioppi, L. Ortona, A. De Luca, N. Petrosillo, P. Noto, P. Salcuni, P. De Longis, M. Lichtner, G. Pastore, G. Minafra, L. Loiacono, M. Piazza, S. Nappa, N. Abrescia, M. De Marco, A. Colomba, T. Prestileo, C. De Stefano, A. La Gala, T. Ferraro, A. Scerbo, P. Grima, P. Tundo, E. Pizzigallo, M. D'Alessandro, B. Grisorio, S. Ferrara, C. Caissotti, P. Dellamonica, L. Bentz, E. Bernard, S. Chaillou, F. De Salvador-Guillouet, J. Durant, R. Guttman, L. Heripret, V. Mondain-Miton, I. Perbost, B. Prouvost-Keller, P. Pugliese, V. Rahelinirina, P. M. Roger, F. Vandenbos, E. Bernasconi, H. Bucher, P. Bürgisser, S. Cattacin, M. Egger, P. Erb, W. Fierz, M. Fischer, M. Flepp, A. Fontana, H. J. Furrer, M. Gorgievski, H. Günthard, L. Kaiser, C. Kind, T. Klimkait, U. Lauper, M. Opravil, F. Paccaud, G. Pantaleo, L. Perrin, J. C. Piffaretti, C. Rudin, J. Schüpbach, R. Speck, A. Trkola, P. Vernazza, S. Yerly

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1376 Scopus citations

Abstract

BACKGROUND: It remains controversial whether exposure to combination antiretroviral treatment increases the risk of myocardial infarction. METHOD: In this prospective observational study, we enrolled 23,468 patients from 11 previously established cohorts from December 1999 to April 2001 and collected follow-up data until February 2002. Data were collected on infection with the human immunodeficiency virus and on risk factors for and the incidence of myocardial infarction. Relative rates were calculated with Poisson regression models. Combination antiretroviral therapy was defined as any combination regimen of antiretroviral drugs that included a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor. RESULTS: Over a period of 36,199 person-years, 126 patients had a myocardial infarction. The incidence of myocardial infarction increased with longer exposure to combination antiretroviral therapy (adjusted relative rate per year of exposure, 1.26 [95 percent confidence interval, 1.12 to 1.41]; P<0.001). Other factors significantly associated with myocardial infarction were older age, current or former smoking, previous cardiovascular disease, and male sex, but not a family history of coronary heart disease. A higher total serum cholesterol level, a higher triglyceride level, and the presence of diabetes were also associated with an increased incidence of myocardial infarction. CONCLUSIONS: Combination antiretroviral therapy was independently associated with a 26 percent relative increase in the rate of myocardial infarction per year of exposure during the first four to six years of use. However, the absolute risk of myocardial infarction was low and must be balanced against the marked benefits from antiretroviral treatment.

Original languageEnglish (US)
Pages (from-to)1993-2003
Number of pages11
JournalNew England Journal of Medicine
Volume349
Issue number21
DOIs
StatePublished - Nov 20 2003

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