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: a multi-cohort collaboration
AU - Mancuso, Salvatrice
AU - Sawitz, null
AU - Kjær, null
AU - Poll, null
AU - Rickenbach, null
AU - Worm, Signe W.
AU - Lundgren, Jens D.
AU - Phillips, Andrew N.
AU - De Wit, Stephane
AU - Law, Matthew
AU - Collins, null
AU - Fontas, null
AU - Sabin, Caroline A.
AU - El-Sadr, Wafaa
AU - Krum, null
AU - Torres, null
AU - Sundström, null
AU - Rosseau, null
AU - Torres, null
AU - Friis-Møller, Nina
AU - Sawitz, null
AU - Torres, null
AU - Pradier, Christian
AU - Weber, Rainer
AU - Torres, Ferran
AU - Torres, null
AU - Petoumenos, null
AU - Storfer, null
AU - Sjøl, null
AU - Reiss, Peter
AU - Pezzotti, null
AU - Kirk, Ole
AU - Weller, Ian
AU - Neaton, null
AU - D'Arminio Monforte, Antonella
AU - Rickenbach, null
AU - Dabis, Francois
AU - Torres, null
AU - Hammer, null
AU - Weber, Rainer
AU - Balestre, null
AU - Gras, null
PY - 2008
Y1 - 2008
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 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. Funding: HAART Oversight Committee. © 2008 Elsevier Ltd. All rights reserved.
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 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. Funding: HAART Oversight Committee. © 2008 Elsevier Ltd. All rights reserved.
KW - 80 and over; Didanosine; Dideoxynucleosides; Female; HIV Infections; Humans; Male; Middle Aged; Myocardial Infarction; Poisson Distribution; Reverse Transcriptase Inhibitors; Risk Factors; Medicine (all)
KW - Adult; Aged; Aged
KW - 80 and over; Didanosine; Dideoxynucleosides; Female; HIV Infections; Humans; Male; Middle Aged; Myocardial Infarction; Poisson Distribution; Reverse Transcriptase Inhibitors; Risk Factors; Medicine (all)
KW - Adult; Aged; Aged
UR - http://hdl.handle.net/10447/215307
UR - http://www.journals.elsevier.com/the-lancet/
M3 - Article
VL - 371
SP - 1417
EP - 1426
JO - The Lancet
JF - The Lancet
SN - 0140-6736
ER -