TY - JOUR
T1 - Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study
T2 - A multi-cohort collaboration
AU - Sabin, Caroline A.
AU - Worm, Signe W.
AU - Weber, Rainer
AU - Reiss, Peter
AU - El-Sadr, Wafaa
AU - Dabis, Francois
AU - De Wit, Stephane
AU - Law, Matthew
AU - D'Arminio Monforte, Antonella
AU - Friis-Møller, Nina
AU - Kirk, Ole
AU - Pradier, Christian
AU - Weller, Ian
AU - Phillips, Andrew N.
AU - Lundgren, Jens D.
AU - Collins, S.
AU - Rosseau, F.
AU - Storfer, S. P.
AU - Sjøl, A.
AU - Sawitz, A.
AU - Rickenbach, M.
AU - Pezzotti, P.
AU - Krum, E.
AU - Gras, L.
AU - Balestre, E.
AU - Sundström, A.
AU - Poll, B.
AU - Fontas, E.
AU - Torres, F.
AU - Petoumenos, K.
AU - Kjær, J.
AU - Hammer, S.
AU - Neaton, J.
AU - D:A:D Study Group
PY - 2008/1/1
Y1 - 2008/1/1
N2 - 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 aff ected 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 signifi cantly 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.
AB - 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 aff ected 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 signifi cantly 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.
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U2 - 10.1016/S0140-6736(08)60423-7
DO - 10.1016/S0140-6736(08)60423-7
M3 - Article
C2 - 18387667
SN - 0140-6736
VL - 371
SP - 1417
EP - 1426
JO - The Lancet
JF - The Lancet
IS - 9622
ER -