WACS 2007Low.
Methods | Women's Antioxidant Cardiovascular Study (WACS). Randomised, double‐blind, placebo‐controlled trial using two‐by‐two‐by‐two factorial design and than two‐by‐two‐by‐two‐by‐two design. |
|
Participants | Country: United States of America. Number of participants randomised: 8171 female health professionals aged 40 years or older, mean age 60.6 years, with a history of cardiovascular disease or three or more cardiovascular risk factors. Inclusion criteria: 40 years or older, postmenopausal, or had no intention of becoming pregnant, had a self reported history of cardiovascular disease, or had at least three cardiac risk factors (self reported diagnosis of hypertension, high cholesterol level, or diabetes mellitus); parental history of premature myocardial infarction (MI) (before age 60 years); obesity (body mass index (BMI) ≥ 30), current cigarette smoking; and inconsistent report of prior cardiovascular disease. Exclusion criteria: self‐reported history of cancer (excluding nonmelanoma skin cancer) within the past 10 years, any serious non‐cardiovascular illness, or were currently using warfarin sodium or other anticoagulants. |
|
Interventions | Participants were randomly assigned to receive: group 1: active vitamin C (synthetic vitamin C) 500 mg daily, active vitamin E (d‐alpha tocopherol acetate) 600 IU every other day, and beta‐carotene (Lurotin) 50 mg, every other day (n = 1020); group 2: active vitamin C (synthetic vitamin C) 500 mg daily, active vitamin E (d‐alpha tocopherol acetate) 600 IU every other day, and placebo beta‐carotene (Lurotin) 50 mg, every other day (n = 1021); group 3: active vitamin C (synthetic vitamin C) 500 mg daily, placebo vitamin E every other day, and beta‐carotene (Lurotin) 50 mg, every other day (n = 1023); group 4: active vitamin C (synthetic vitamin C) 500 mg daily, placebo vitamin E every other day, and placebo beta‐carotene, every other day (n = 1023); group 5: placebo vitamin C daily, active vitamin E (d‐alpha tocopherol acetate) 600 IU every other day, and beta‐carotene (Lurotin) 50 mg, every other day (n = 1021); group 6: placebo vitamin C daily, active vitamin E (d‐alpha tocopherol acetate) 600 IU every other day, and placebo beta‐carotene every other day (n = 1021); group 7: placebo vitamin C daily, placebo vitamin E every other day, and beta‐carotene (Lurotin) 50 mg, every other day (n = 1020); group 8: placebo vitamin C daily, placebo vitamin E every other day, and placebo beta‐carotene every other day (n = 1022); for a mean period of 9.4 years (range, 8.3 to 10.1 years). In 1998, approximately 2 to 3 years following randomisation to the antioxidant arms, a folic acid ‐ vitamin B6/B12 component was added to the trial, expanding it to a two‐by‐two‐by‐two‐by‐two factorial trial. |
|
Outcomes | The primary outcome was a combined end point of CVD morbidity and mortality, including incident myocardial infarction, stroke, coronary revascularization procedures (coronary artery bypass grafting or percutaneous transluminal coronary angioplasty), and cardiovascular mortality. Secondary outcome measures were myocardial infarction, stroke, coronary revascularisation, and cardiovascular death. Information on transient ischaemic attack and total mortality was also collected. | |
Notes | Between June 1995 and October 1996, a total of 8171 women were randomly assigned according to a two‐by‐two‐by‐two factorial design. Study treatment and endpoint ascertainment were continued in a blinded fashion through January 31, 2005, the scheduled end of the trial. Compliance was assessed through self‐report and defined as taking at least two‐thirds of study pills. Reported compliance was, on average, 76% at four years and 68% at eight years of follow‐up for each antioxidant, with no significant difference between active and placebo groups at these times except for ascorbic acid at eight years (70% versus 67% in the active versus placebo group). Mean compliance over follow‐up was approximately 73% for all active and placebo agents. Overall, vital status was known for 93.3% of randomised participants. Vitamin C and beta carotene were supplied by BASF Corp (Wyandotte, MI) and vitamin E was supplied by (Cognis Corp, LaGrange, Il). |
|
Risk of bias | ||
Bias | Authors' judgement | Support for judgement |
Random sequence generation (selection bias) | Low risk | Sequence generation was achieved using computer random number generation. |
Allocation concealment (selection bias) | Low risk | Allocation was controlled by a central and independent randomisation unit so that intervention allocations could not have been foreseen in advance of, or during, enrolment. |
Blinding (performance bias and detection bias) All outcomes | Low risk | The trial was described as blinded, the parties that were blinded, and the method of blinding was described, so that knowledge of allocation was adequately prevented during the trial. |
Incomplete outcome data (attrition bias) All outcomes | Low risk | The numbers and reasons for dropouts and withdrawals in all intervention groups were described. |
Selective reporting (reporting bias) | Low risk | Pre‐defined, or clinically relevant and reasonably expected outcomes are reported on. |
Other bias | Low risk | The trial appears to be free of other components that could put it at risk of bias. |