Oral high-dose multivitamins and minerals after myocardial infarction: a randomized trial
Gervasio A Lamas, Robin Boineau, Christine Goertz, Daniel B Mark, Yves Rosenberg, Mario Stylianou, Theodore Rozema, Richard L Nahin, Lauren Lindblad, Eldrin F Lewis, Jeanne Drisko, Kerry L Lee, TACT (Trial to Assess Chelation Therapy) Investigators, Narendra Bhalodkar, Noneta Montinola, Allan Magaziner, Betty Ann Persico, Raymond Magorien, Luba Mazanec, Pamela Ouyang, Jeanne Wingo, Mara Slawsky, Judith Fleurent, Russell Silverman, Sherri Loucks, Robert Weiss, Diana Cass, Robert Berke, Paige Davidson, Robert Bulgarelli, Susan Herring, Steven Sedlis, Estelita Anteola, Austin Halle, Lian Yang, Majid Ali, Mahboobullah Baig, Alexander Poulathas, Linda Dewey, Harmony Reynolds, Chao Wang, Kenneth Bock, Debbie Truin, Michael Schachter, Sally Minniefield, Yulius Poplyansky, Yulius Poplyansky, Marjorie Patino, Stuart Freedenfeld, Verna Good, Glenn Gerber, Patricia O'Brien, Terry Chappell, Marcia Arnold, Ralph Miranda, Barb Casella, James Lafferty, Lenora Tafuri-Acevedo, Guy Pugh, Vivian Cole, James Garofalo, Krystle Chavez, James Roberts, Debra Braun, James Johnson, Rosemary Stevenson, Ivan Krohn, Lewis S Korb, Jack Slingluff, John Mountford, Robert Schmidt, Evelyn Alentin, Lisa Lichota, Keith Rost, Sean McCloy, Richard Plumb, Lynn Shough, Linda Bunch, April Archey, Lisa Merritt, Lisa Lockett, Steven Borzak, Dina Herig, Joseph Bissett, Sandra McLaren, Joseph Bissett, Sharon Locke, Joseph O'Bryan, Mary Barr, Shalendra Varma, Ricky Schneider, Rochelle Mckenzie, James Carter, Kaylynn LeBlanc, Joseph Holliday, Vivian Holliday, Theodore Rozema, Dolly Corbin, Robert Ciccia-Maclean, Pablo Guala, Todd Heimowitz, Helen Garcia, Roy Heilbron, Celia Heilbron, Angelique Hart, Barry Katzen, Ivette Cruz, Donald Tice, Sangeeta Shah, Debbie Vige, John Griffin, Pam Hollsten, Jack Young, Estela Fransbergen, Rajiv Chandra, Terry Murphy, Mark Speight, Janine Speight, Smart Idemudia, Geneve Gutierrez, Lawrence Miller, Deanna Overbeck, Clayton Bredlau, Amy Heineman, Timothy Blend, Helena Williams, Miguel Trevino, Kimberly Mai, Jose Oblena, Bonita Harris, Dorothy Merritt, Elizabeth Collins, Pieter deWet, Cindy deWet, Gerald Wootan, Susan Shaw, Connie Ross, Michelle Simpson, Clinton Corder, Michael Stout, Robert Wright, Alma Steffen, John Sullebarger, Leona Stewart, Carol Roberts, Berni McClendon, Nelzon Kraucak, Mariann Haring, Linda Bunch, Shauna Gallien, R J Oenbrink, Joe Militello, Charles Adams, Jackie Miles, Karen Dantin, Laurie McDuff, Leslie Fleischer, Cheri Penas, Marina M Pearsall, Jeffrey Mueller, Linda Bunch, Kim Robinson, Paul Kotturan, Nalini Reddy, Robert C Allen, Laura Whitaker, Rajinder Bhalla, Teresa Hicks, Hector Fontanet, Precious Hoyle, Albert Zant, Michelle Potpan, Greg Flaker, Sharon Clasby, Jonathan Ehrman, Matthew Saval, Jeanne Drisko, Elizabeth Schrick, Robert Waters, Sarah B Chapman, Donald Riemer, Laura Sembach, Varsha Rathod, Heather Moran, Tammy Born, Judy Schneider, Steven Windley, Stephanie Pyle, Gerald Gau, Dawn Shelstad, Richard Grimm, Mary Perron, Eric Born, Julie Ladkrood, Kenneth Ganapini, Venus Barney, Robert Randall, Teresa Kohle, Hector Marchand, Cheryl Kwiatkowski, Anita Arnold, Dana Kappel, Timothy Logeman, Karen Olson, Ron Hunninghake, Mavis Schultz, Brian Dieterle, Debra Louderback, Marjon Fariba, Sepideh Arvin Matthew, Zbigniew Grudzien, Marinela Matei, Richard Dexter, Christine Rupley, Ronald Karlsberg, Tracey S Gerez, Patrick Golden, Kathy Sasser, Nampalli Vijay, Melinda Washam, Richard Casdorph, Heather Browning, Chris Hatlestad, Christine Ohlemann, Paul Peterson, Lori Heaney, Erminia Guarneri, Eva Stuart, Terry Grossman, Kathryn Bottinell, Vishal Patel, Denise Wells, William David Voss, Lorna Gordon, Eric Gordon, Win Bertrand, Eleanor Hynote, Katie Lacey, Ann McCombs, Arlene Sellereite, Chris Hatlestad, Cambor Wade, Bruce McLellan, Noura Sall, Richard Nahas, Shadi Nahas, Arun Dosaj, Diane Dosaj, Shmuel Bergman, Mary Toro, Ben Boucher, Robyn Whitty, Paul Jaconello, Hildegard Beath, John Gannage, Tony Estacio, Fred Hui, Eva Pacaba, Edward Nykiforuk, Val Kalyn, Clare Minielly, François Reeves, Jean Aubry, Barbara Brooks, Jean-Claude Tardif, Randa Zamrini, John Cline, Frank Pluta, Gervasio A Lamas, Robin Boineau, Christine Goertz, Daniel B Mark, Yves Rosenberg, Mario Stylianou, Theodore Rozema, Richard L Nahin, Lauren Lindblad, Eldrin F Lewis, Jeanne Drisko, Kerry L Lee, TACT (Trial to Assess Chelation Therapy) Investigators, Narendra Bhalodkar, Noneta Montinola, Allan Magaziner, Betty Ann Persico, Raymond Magorien, Luba Mazanec, Pamela Ouyang, Jeanne Wingo, Mara Slawsky, Judith Fleurent, Russell Silverman, Sherri Loucks, Robert Weiss, Diana Cass, Robert Berke, Paige Davidson, Robert Bulgarelli, Susan Herring, Steven Sedlis, Estelita Anteola, Austin Halle, Lian Yang, Majid Ali, Mahboobullah Baig, Alexander Poulathas, Linda Dewey, Harmony Reynolds, Chao Wang, Kenneth Bock, Debbie Truin, Michael Schachter, Sally Minniefield, Yulius Poplyansky, Yulius Poplyansky, Marjorie Patino, Stuart Freedenfeld, Verna Good, Glenn Gerber, Patricia O'Brien, Terry Chappell, Marcia Arnold, Ralph Miranda, Barb Casella, James Lafferty, Lenora Tafuri-Acevedo, Guy Pugh, Vivian Cole, James Garofalo, Krystle Chavez, James Roberts, Debra Braun, James Johnson, Rosemary Stevenson, Ivan Krohn, Lewis S Korb, Jack Slingluff, John Mountford, Robert Schmidt, Evelyn Alentin, Lisa Lichota, Keith Rost, Sean McCloy, Richard Plumb, Lynn Shough, Linda Bunch, April Archey, Lisa Merritt, Lisa Lockett, Steven Borzak, Dina Herig, Joseph Bissett, Sandra McLaren, Joseph Bissett, Sharon Locke, Joseph O'Bryan, Mary Barr, Shalendra Varma, Ricky Schneider, Rochelle Mckenzie, James Carter, Kaylynn LeBlanc, Joseph Holliday, Vivian Holliday, Theodore Rozema, Dolly Corbin, Robert Ciccia-Maclean, Pablo Guala, Todd Heimowitz, Helen Garcia, Roy Heilbron, Celia Heilbron, Angelique Hart, Barry Katzen, Ivette Cruz, Donald Tice, Sangeeta Shah, Debbie Vige, John Griffin, Pam Hollsten, Jack Young, Estela Fransbergen, Rajiv Chandra, Terry Murphy, Mark Speight, Janine Speight, Smart Idemudia, Geneve Gutierrez, Lawrence Miller, Deanna Overbeck, Clayton Bredlau, Amy Heineman, Timothy Blend, Helena Williams, Miguel Trevino, Kimberly Mai, Jose Oblena, Bonita Harris, Dorothy Merritt, Elizabeth Collins, Pieter deWet, Cindy deWet, Gerald Wootan, Susan Shaw, Connie Ross, Michelle Simpson, Clinton Corder, Michael Stout, Robert Wright, Alma Steffen, John Sullebarger, Leona Stewart, Carol Roberts, Berni McClendon, Nelzon Kraucak, Mariann Haring, Linda Bunch, Shauna Gallien, R J Oenbrink, Joe Militello, Charles Adams, Jackie Miles, Karen Dantin, Laurie McDuff, Leslie Fleischer, Cheri Penas, Marina M Pearsall, Jeffrey Mueller, Linda Bunch, Kim Robinson, Paul Kotturan, Nalini Reddy, Robert C Allen, Laura Whitaker, Rajinder Bhalla, Teresa Hicks, Hector Fontanet, Precious Hoyle, Albert Zant, Michelle Potpan, Greg Flaker, Sharon Clasby, Jonathan Ehrman, Matthew Saval, Jeanne Drisko, Elizabeth Schrick, Robert Waters, Sarah B Chapman, Donald Riemer, Laura Sembach, Varsha Rathod, Heather Moran, Tammy Born, Judy Schneider, Steven Windley, Stephanie Pyle, Gerald Gau, Dawn Shelstad, Richard Grimm, Mary Perron, Eric Born, Julie Ladkrood, Kenneth Ganapini, Venus Barney, Robert Randall, Teresa Kohle, Hector Marchand, Cheryl Kwiatkowski, Anita Arnold, Dana Kappel, Timothy Logeman, Karen Olson, Ron Hunninghake, Mavis Schultz, Brian Dieterle, Debra Louderback, Marjon Fariba, Sepideh Arvin Matthew, Zbigniew Grudzien, Marinela Matei, Richard Dexter, Christine Rupley, Ronald Karlsberg, Tracey S Gerez, Patrick Golden, Kathy Sasser, Nampalli Vijay, Melinda Washam, Richard Casdorph, Heather Browning, Chris Hatlestad, Christine Ohlemann, Paul Peterson, Lori Heaney, Erminia Guarneri, Eva Stuart, Terry Grossman, Kathryn Bottinell, Vishal Patel, Denise Wells, William David Voss, Lorna Gordon, Eric Gordon, Win Bertrand, Eleanor Hynote, Katie Lacey, Ann McCombs, Arlene Sellereite, Chris Hatlestad, Cambor Wade, Bruce McLellan, Noura Sall, Richard Nahas, Shadi Nahas, Arun Dosaj, Diane Dosaj, Shmuel Bergman, Mary Toro, Ben Boucher, Robyn Whitty, Paul Jaconello, Hildegard Beath, John Gannage, Tony Estacio, Fred Hui, Eva Pacaba, Edward Nykiforuk, Val Kalyn, Clare Minielly, François Reeves, Jean Aubry, Barbara Brooks, Jean-Claude Tardif, Randa Zamrini, John Cline, Frank Pluta
Abstract
Background: Whether high-dose multivitamins are effective for secondary prevention of atherosclerotic disease is unknown.
Objective: To assess whether oral multivitamins reduce cardiovascular events and are safe.
Design: Double-blind, placebo-controlled, 2 x 2 factorial, multicenter, randomized trial. (ClinicalTrials.gov: NCT00044213) SETTING: 134 U.S. and Canadian academic and clinical sites.
Patients: 1708 patients aged 50 years or older who had myocardial infarction (MI) at least 6 weeks earlier and had serum creatinine levels of 176.8 mol/L (2.0 mg/dL) or less.
Intervention: Patients were randomly assigned to an oral, 28-component, high-dose multivitamin and multimineral mixture or placebo.
Measurements: The primary end point was time to total death, recurrent MI, stroke, coronary revascularization, or hospitalization for angina.
Results: The median age was 65 years, and 18% of patients were women. The qualifying MI occurred a median of 4.6 years (interquartile range [IQR], 1.6 to 9.2 years) before enrollment. Median follow-up was 55 months (IQR, 26 to 60 months). Patients received vitamins for a median of 31 months (IQR, 13 to 59 months) in the vitamin group and 35 months (IQR, 13 to 60 months) in the placebo group (P = 0.65). Totals of 645 (76%) and 646 (76%) patients in the vitamin and placebo groups, respectively, completed at least 1 year of oral therapy (P = 0.98), and 400 (47%) and 426 (50%) patients, respectively, completed at least 3 years (P = 0.23). Totals of 394 (46%) and 390 (46%) patients in the vitamin and placebo groups, respectively, discontinued the vitamin regimen (P = 0.67), and 17% of patients withdrew from the study. The primary end point occurred in 230 (27%) patients in the vitamin group and 253 (30%) in the placebo group (hazard ratio, 0.89 [95% CI, 0.75 to 1.07]; P = 0.21). No evidence suggested harm from vitamin therapy in any category of adverse events.
Limitation: There was considerable nonadherence and withdrawal, limiting the ability to draw firm conclusions (particularly about safety).
Conclusion: High-dose oral multivitamins and multiminerals did not statistically significantly reduce cardiovascular events in patients after MI who received standard medications. However, this conclusion is tempered by the nonadherence rate.
Primary funding source: National Institutes of Health.
Figures
Source: PubMed