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

D:A:D study Group

doi:10.1016/S0140-6736(08)60423-7

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

D:A:D study Group

Mailman School of Public Health

Research output: Contribution to journal › Article › peer-review

809 Citations (Scopus)

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 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.

Original language	English
Pages (from-to)	1417-1426
Number of pages	10
Journal	The Lancet
Volume	371
Issue number	9622
DOIs	https://doi.org/10.1016/S0140-6736(08)60423-7
Publication status	Published - 2008

Bibliographical note

Funding Information:
The D:A:D study is funded by the HAART Oversight Committee, an European Medicines Evaluation Agency (EMEA) initiative supported by Abbott Laboratories, AIDS Treatment Activists Collation (ATAC), Boehringer-Ingelheim Pharmaceuticals, Bristol-Myers Squibb, European AIDS Treatment Group (EATG), US Food and Drug Administration (FDA), F Hoffmann-La Roche, Gilead Sciences, GlaxoSmithKline, Merck & Co, and Pfizer. Further support for participating cohorts: a grant from the Health Insurance Fund Council (CURE/97/46486), Amstelveen, Netherlands, to the AIDS Therapy Evaluation Project Netherlands (ATHENA); by a grant from the Agence Nationale de Recherches sur le SIDA (Action Coordonnée no 7, Cohortes), to the Aquitaine Cohort; by the Australian Government Department of Health and Ageing, and by grant no UOI069907 from the US National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID) to the Australian HIV Observational Database (AHOD); by grants from the Fondo de Investigación Sanitaria (FIS 99/0887) and Fundación para la Investigación y la Prevención del SIDA en Espanã (FIPSE 3171/00), to the Barcelona Antiretroviral Surveillance Study (BASS); by the NIH NIAID (grants 5U01AI042170-10 and 5U01AI046362-03), to the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA); the European Commission BIOMED 1 (CT94-1637), BIOMED 2 (CT97-2713), the 5th Framework (QLK2-2000-00773) and the 6th Framework (LSHP-CT-2006-018632) programmes were the primary sponsors of the study. Unrestricted grants were also provided by Bristol-Myers Squibb, GlaxoSmithKline, Roche, Gilead, Pfizer, Merck and Co, Tibotec, and Boehringer-Ingelheim. The participation of centres from Switzerland was supported by a grant from the Swiss Federal Office for Education and Science (EuroSIDA); by an unrestricted educational grant from Glaxo Wellcome, Italy, to the Italian Cohort Naive to Antiretrovirals (ICONA); and by a grant from the Swiss National Science Foundation, to the Swiss HIV Cohort Study (SHCS).

Funding

The D:A:D study is funded by the HAART Oversight Committee, an European Medicines Evaluation Agency (EMEA) initiative supported by Abbott Laboratories, AIDS Treatment Activists Collation (ATAC), Boehringer-Ingelheim Pharmaceuticals, Bristol-Myers Squibb, European AIDS Treatment Group (EATG), US Food and Drug Administration (FDA), F Hoffmann-La Roche, Gilead Sciences, GlaxoSmithKline, Merck & Co, and Pfizer. Further support for participating cohorts: a grant from the Health Insurance Fund Council (CURE/97/46486), Amstelveen, Netherlands, to the AIDS Therapy Evaluation Project Netherlands (ATHENA); by a grant from the Agence Nationale de Recherches sur le SIDA (Action Coordonnée no 7, Cohortes), to the Aquitaine Cohort; by the Australian Government Department of Health and Ageing, and by grant no UOI069907 from the US National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID) to the Australian HIV Observational Database (AHOD); by grants from the Fondo de Investigación Sanitaria (FIS 99/0887) and Fundación para la Investigación y la Prevención del SIDA en Espanã (FIPSE 3171/00), to the Barcelona Antiretroviral Surveillance Study (BASS); by the NIH NIAID (grants 5U01AI042170-10 and 5U01AI046362-03), to the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA); the European Commission BIOMED 1 (CT94-1637), BIOMED 2 (CT97-2713), the 5th Framework (QLK2-2000-00773) and the 6th Framework (LSHP-CT-2006-018632) programmes were the primary sponsors of the study. Unrestricted grants were also provided by Bristol-Myers Squibb, GlaxoSmithKline, Roche, Gilead, Pfizer, Merck and Co, Tibotec, and Boehringer-Ingelheim. The participation of centres from Switzerland was supported by a grant from the Swiss Federal Office for Education and Science (EuroSIDA); by an unrestricted educational grant from Glaxo Wellcome, Italy, to the Italian Cohort Naive to Antiretrovirals (ICONA); and by a grant from the Swiss National Science Foundation, to the Swiss HIV Cohort Study (SHCS).

Funders	Funder number
5th Framework	QLK2-2000-00773
6th Framework	LSHP-CT-2006-018632
AIDS Treatment Activists Collation
BIOMED	CT97-2713
Boehringer-Ingelheim Pharmaceuticals
European AIDS Treatment Group
European Commission BIOMED	CT94-1637
European Medicines Evaluation Agency
Fondo de Investigación Sanitaria	FIS 99/0887
Fundación para la Investigación y la Prevención del Sida en Espanã	FIPSE 3171/00
Glaxo Wellcome
Health Insurance Fund Council	CURE/97/46486
National Institutes of Health
U.S. Food and Drug Administration
National Institute of Allergy and Infectious Diseases	5U01AI046362-03, U01AI069907, 5U01AI042170-10
Abbott Laboratories
Bristol-Myers Squibb
Pfizer
GlaxoSmithKline
Merck
Gilead Sciences
F. Hoffmann-La Roche
Department of Health and Ageing, Australian Government	UOI069907
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Agence Nationale de Recherches sur le Sida et les Hépatites Virales
Office Fédéral de l'Education et de la Science

ASJC Scopus Subject Areas

General Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/S0140-6736(08)60423-7

Cite this

@article{15440c17ff40499f8a54f8918c2b2a90,

title = "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",

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 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.",

author = "{D:A:D study Group} and Sabin, {Caroline A.} and Worm, {Signe W.} and Rainer Weber and Peter Reiss and Wafaa El-Sadr and Francois Dabis and {De Wit}, Stephane and Matthew Law and {D'Arminio Monforte}, Antonella and Nina Friis-M{\o}ller and Ole Kirk and Christian Pradier and Ian Weller and Phillips, {Andrew N.} and Lundgren, {Jens D.} and S. Collins and F. Rosseau and Storfer, {S. P.} and A. Sj{\o}l and A. Sawitz and M. Rickenbach and P. Pezzotti and E. Krum and L. Gras and E. Balestre and A. Sundstr{\"o}m and B. Poll and E. Fontas and F. Torres and K. Petoumenos and J. Kj{\ae}r and S. Hammer and J. Neaton",

note = "Funding Information: The D:A:D study is funded by the HAART Oversight Committee, an European Medicines Evaluation Agency (EMEA) initiative supported by Abbott Laboratories, AIDS Treatment Activists Collation (ATAC), Boehringer-Ingelheim Pharmaceuticals, Bristol-Myers Squibb, European AIDS Treatment Group (EATG), US Food and Drug Administration (FDA), F Hoffmann-La Roche, Gilead Sciences, GlaxoSmithKline, Merck & Co, and Pfizer. Further support for participating cohorts: a grant from the Health Insurance Fund Council (CURE/97/46486), Amstelveen, Netherlands, to the AIDS Therapy Evaluation Project Netherlands (ATHENA); by a grant from the Agence Nationale de Recherches sur le SIDA (Action Coordonn{\'e}e no 7, Cohortes), to the Aquitaine Cohort; by the Australian Government Department of Health and Ageing, and by grant no UOI069907 from the US National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID) to the Australian HIV Observational Database (AHOD); by grants from the Fondo de Investigaci{\'o}n Sanitaria (FIS 99/0887) and Fundaci{\'o}n para la Investigaci{\'o}n y la Prevenci{\'o}n del SIDA en Espan{\~a} (FIPSE 3171/00), to the Barcelona Antiretroviral Surveillance Study (BASS); by the NIH NIAID (grants 5U01AI042170-10 and 5U01AI046362-03), to the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA); the European Commission BIOMED 1 (CT94-1637), BIOMED 2 (CT97-2713), the 5th Framework (QLK2-2000-00773) and the 6th Framework (LSHP-CT-2006-018632) programmes were the primary sponsors of the study. Unrestricted grants were also provided by Bristol-Myers Squibb, GlaxoSmithKline, Roche, Gilead, Pfizer, Merck and Co, Tibotec, and Boehringer-Ingelheim. The participation of centres from Switzerland was supported by a grant from the Swiss Federal Office for Education and Science (EuroSIDA); by an unrestricted educational grant from Glaxo Wellcome, Italy, to the Italian Cohort Naive to Antiretrovirals (ICONA); and by a grant from the Swiss National Science Foundation, to the Swiss HIV Cohort Study (SHCS). ",

year = "2008",

doi = "10.1016/S0140-6736(08)60423-7",

language = "English",

volume = "371",

pages = "1417--1426",

journal = "The Lancet",

issn = "0140-6736",

publisher = "Elsevier Limited",

number = "9622",

}

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 - D:A:D study Group

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.

N1 - Funding Information: The D:A:D study is funded by the HAART Oversight Committee, an European Medicines Evaluation Agency (EMEA) initiative supported by Abbott Laboratories, AIDS Treatment Activists Collation (ATAC), Boehringer-Ingelheim Pharmaceuticals, Bristol-Myers Squibb, European AIDS Treatment Group (EATG), US Food and Drug Administration (FDA), F Hoffmann-La Roche, Gilead Sciences, GlaxoSmithKline, Merck & Co, and Pfizer. Further support for participating cohorts: a grant from the Health Insurance Fund Council (CURE/97/46486), Amstelveen, Netherlands, to the AIDS Therapy Evaluation Project Netherlands (ATHENA); by a grant from the Agence Nationale de Recherches sur le SIDA (Action Coordonnée no 7, Cohortes), to the Aquitaine Cohort; by the Australian Government Department of Health and Ageing, and by grant no UOI069907 from the US National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID) to the Australian HIV Observational Database (AHOD); by grants from the Fondo de Investigación Sanitaria (FIS 99/0887) and Fundación para la Investigación y la Prevención del SIDA en Espanã (FIPSE 3171/00), to the Barcelona Antiretroviral Surveillance Study (BASS); by the NIH NIAID (grants 5U01AI042170-10 and 5U01AI046362-03), to the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA); the European Commission BIOMED 1 (CT94-1637), BIOMED 2 (CT97-2713), the 5th Framework (QLK2-2000-00773) and the 6th Framework (LSHP-CT-2006-018632) programmes were the primary sponsors of the study. Unrestricted grants were also provided by Bristol-Myers Squibb, GlaxoSmithKline, Roche, Gilead, Pfizer, Merck and Co, Tibotec, and Boehringer-Ingelheim. The participation of centres from Switzerland was supported by a grant from the Swiss Federal Office for Education and Science (EuroSIDA); by an unrestricted educational grant from Glaxo Wellcome, Italy, to the Italian Cohort Naive to Antiretrovirals (ICONA); and by a grant from the Swiss National Science Foundation, to the Swiss HIV Cohort Study (SHCS).

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 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.

UR - http://www.scopus.com/inward/record.url?scp=42649130015&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42649130015&partnerID=8YFLogxK

U2 - 10.1016/S0140-6736(08)60423-7

DO - 10.1016/S0140-6736(08)60423-7

M3 - Article

C2 - 18387667

AN - SCOPUS:42649130015

SN - 0140-6736

VL - 371

SP - 1417

EP - 1426

JO - The Lancet

JF - The Lancet

IS - 9622

ER -

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

Abstract

Bibliographical note

Funding

ASJC Scopus Subject Areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this