Presentation on theme: "Journal Club Hallie Lee PharmD Candidate 2013 Mercer University COPHS PHA 618 Geriatrics-Continuous Care Multivitamins in the Prevention of Cardiovascular."— Presentation transcript:
Journal Club Hallie Lee PharmD Candidate 2013 Mercer University COPHS PHA 618 Geriatrics-Continuous Care Multivitamins in the Prevention of Cardiovascular Disease in Men; The Physicians’ Health Study II Randomized Controlled Trial
Introduction: The PHS PHS = Physicians’ Health Study II Multivitamins, the most common supplement taken by US adults, are used to prevent vitamin and mineral deficiency Perception that they may prevent cardiovascular disease Observational studies have shown inconsistent associations There are no long-term clinical trials of their use for CVD TO DETERMINE WHETHER LONG-TERM MULTIVITAMIN SUPPLEMENTATION DECREASES THE RISK OF MAJOR CARDIOVASCULAR EVENTS AMONG MEN (Results for cancer, eye disease, and cognitive decline are to be published separately)
Methods Randomized, double-blind, placebo-controlled 2x2x2x2 factorial trial of common daily multivitamin Phase 1: July 1997 18,763 men from PHS I Phase 2: July 1999 By July 2011 42,165 recruited In total 14,641 male US physicians initially aged 50 754 with a history of CVD at randomization
Methods Stratified by age, prior cancer or CVD, & PHS I assignment Multivitamin Vitamin E Vitamin C Beta carotene Exclusion Criteria History of cirrhosis or acute liver disease Taking anticoagulants Reported serious illness Willing to forgo current use of multivitamins or supplements with >100% the RDA Funded by National Institutes of Health, BASF Corp., Pfizer, and DSM Nutritional Products Inc.
Methods Primary endpoint: Major cardiovascular events (nonfatal MI, nonfatal stroke, and CVD mortality) Secondary endpoints: MI and Stroke individually
Results Rates of major CV events: 11.0 per 1000 person-years in the multivitamin group 10.8 per 1000 person-years in the placebo group Men taking a daily multivitamin experienced no benefit for the primary end point of major CV events (HR, 1.01; 95% CI, 0.91- 1.10; P =.91) Lack of significant benefit for the secondary end points Total MI (3.9 and 4.2 events per 1000 person-years for multivitamin and placebo, respectively; HR, 0.93; 95% CI, 0.80-1.09; P =.39) Total stroke (4.1 and 3.9 events per 1000 person-years; HR, 1.06; 95% CI, 0.91-1.23; P =.48) compared to placebo
Results: Cumulative Incidence Curves A summary curve showing the cumulative failure rates over time due to a particular cause
Results Subgroup analyses examined whether baseline clinical, lifestyle, familial, biochemical, and dietary risk factors for CVD, along with the other randomized PHS II interventions, modified the effect of a daily multivitamin on major cardiovascular events Suggestion of a differential effect across age groups with possible differences among men aged 50 to 59 years and men 70 years or older No other evidence was found of effect modification by baseline risk factors on major CV events
Statistics The PHS II was estimated to have 80%power to detect a 12% reduction in theprimary end point of major CV events Primary analyses were based on theintention-to-treat principle All analyses performed using SASversion 9.2 (SAS Institute Inc) and S-Plus(Insightful Corp), with statisticalsignificance set at P <.05 using 2-sided tests Cox proportional hazards modelsestimated hazard ratios (HRs) and 95%CIs Each pre-specified end point stratifiedon the presence of CVD atrandomization and adjusted for PHS IIstudy design variables, including age,PHS cohort (original PHS I participant,new PHS II participant), and randomizedvitamin E, vitamin C, and beta caroteneassignments
Statistics: A look at “Power” Power is defined by beta ( ) Indicates the probability of the statistical test detecting significant differences when they exist Analogous to sensitivity Defined as 1 - Power of 80% is minimal Power of 90% is ideal A power of 80% means there is a 20% chance of a type II error To falsely conclude that no significant difference exists between populations/samples Due to chance or small sample size
Power Higher power is achieved by increasing the sample size Often overlooked by researchers Tabulated values and formulas are available for calculating the required sample size The smaller the difference between two interventions, the larger the sample size needed
Conclusion DAILY MULTIVITAMIN SUPPLEMENTATION DID NOT REDUCETHE RISK OF MAJORCARDIOVASCULAR EVENTS Whether to take a daily multivitaminrequires consideration of anindividual’s nutritional status, becausethe aim of supplementation is toprevent vitamin and mineraldeficiency, plus consideration of otherpotential effects, including a modestreduction in cancer and otherimportant outcomes in PHS II that willbe reported separately
Discussion Limitations Only one multivitamin formulation Study population was confined to middle-aged and older, predominantly white, male physicians Long-term multivitamin use may be more effective when initiated earlier in life to counter the initiation and progression of atherosclerosis that often begins at an earlier age No recommendation or change in practice should be made based on the information found in this trial Additional trials are necessary Class Ib level of evidence
References Sesso H., Christen W., Bubes V., et al. Multivitamins in the Prevention of Cardiovascular Disease in Men; The Physicians’ Health Study II Randomized Controlled Trial. JAMA November 7, 2012; 308(17):1751-1760.