Nutraceuticals and Cardiovascular Disease: Are we fishing?

Transcription

1 Nutraceuticals and Cardiovascular Disease: Are we fishing? ACC Rockies 2013 March 20,2013 Sheri L. Koshman BScPharm, PharmD, ACPR Assistant Professor, Division of Cardiology, University of Alberta

2 none Conflicts of Interest

3 Overview General supplement use Impact of supplements in CV disease: Multivitamins Fish oils Calcium

4 Let food be thy medicine, and medicine be thy food Hippocrates ( BC)

5 How many of your patients use supplement? 1. 10% 2. 20% 3. 50% 4. 80%

6 42% 53% $27 Billion NCHS Data Brief 2011: 61

7 Number of Supplement Bailey RL. J Nutr 2011;141(2):261-66

8 Types of supplements n = 1,055 Prasad K, et al. Am J Cardiol 2013;111:339-45

9 Supplements: Impact Lack of evidence regarding safety and efficacy Food vs drug classification Beliefs about beneficial effects of supplements: May be less likely to engage in other preventative health behaviors May be less likely to engage in modern, proven medical therapies Adherence Pill burden Financial burden

10 Multivitamins

11 Multivitamins 30% 39% NCHS Data Brief 2011: 61

12 Multivitamins Observational data; sparse and inconsistent Nurses Health Study RR 0.76 (95% CI ) Swedish case-control male RR 0.79 ( ) female RR 0.66 ( ) PHS I no association WHI no association Multiethnic cohort study no association

13 JAMA 2012;308(17)

14 Methodology Randomized, DB, PC, 2 x 2 x 2 x 2 factorial Multivitamin (Centrum Silver) daily Vitamin E 400IU q2d (ended 2007) Vitamin C 500mg daily (ended 2007) Beta-carotene 50mg q2d (ended 2003) Outcomes: Prevention of CV disease Cancer Eye disease Cognitive decline JAMA 2012;308(17)

15 Methodology n=14,641 Male, physicians, > 50 years 1999 thru August 2012 Follow-up: >98%; median 11.2 years Outcomes: Primary: major CV events (non-fatal MI, non-fatal stroke, CVD mortality) Other: total MI, total stroke, total mortality JAMA 2012;308(17)

16 Middle age Regular Exercise Regular ASA Few CVD risk factors Regular fruit/veg JAMA 2012;308(17)

17 Results JAMA 2012;308(17)

18 Conclusions No effect of multivitamins on any CV outcome Limited generalizability: Male, caucasian, physicians healthy good nutritional status at baseline Lack of incremental benefit Small benefit in the prevention of cancer JAMA 2012;308(17)

19 Results: Cancer No difference in cancer mortality Effect the same for secondary prevention JAMA 2012;308(18):

20 Fish Oils

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22 Fish oils: Biologic effects Anti-inflammatory Anti-atherogenic Anti-thrombotic Anti-arrhythmic Lower BP Lower TG

23 JAMA 2012;308(12):

24 Methodology RCT Omega-3 PUFA supplementation in adults Diet or supplements compared to another diet or placebo Primary or secondary CVD Treatment > 1 year Result: 20 studies, 68,680 patients JAMA 2012;308(12):

25 JAMA 2012;308(12):

26 JAMA 2012;308(12):

27 Results No difference: mixed vs. secondary prevention vs. ICD, blinding status or dose JAMA 2012;308(12):

28 JAMA 2012;308(12):

29 Conclusions No significant effect on major CV outcomes across patient populations at increase CV risk Larger effects seen pre-statin era Lack of incremental benefit on top of modern medical therapy Similar results Kwak et al. Arch Intern Med 20012;172: limited to secondary prevention, placebo controlled only Kotwal et al. Circ Cardiovasc Qual Outcomes 2012;5:808-18

30 Fish Oils Courtesy of Elizabeth Woo, RD

31 Calcium

32 Calcium NCHS Data Brief 2011: 61

33 Calcium Calcium is essential for many biological actions Historical data suggested that dietary calcium may be protective against CV disease More recent data suggests that calcium supplementation may increase the risk of CV disease No prospective RCTs to date have investigated the role of calcium supplementation of CV as a primary endpoint

34 Patient and trial level data RCT, PC, calcium > 500mg/d (without Vit D) n=11 trials (12,000) Median follow-up: 3.6 years BMJ 2010;341:c3691doi /bmj.c3691

35 BMJ 2010;341:c3691doi /bmj.c3691

36 BMJ 2011;342:d2040doi: /bmj.d2040

37 Methodology WHI reanalysis (n=36,282): Sub-group analysis of personal use versus no personal use 54% of participant were taking personal calcium 47% of participant were taking personal vitamin D Hypothesis: frequent personal use obscured adverse CV outcomes Meta-analysis Calcium +/- vitamin D use update previous analysis with WHI and non-users of personal calcium at randomization BMJ 2011;342:d2040doi: /bmj.d2040

38 Results: Reanalysis * * * HR Significant interaction with personal use, but not Vitamin D or dietary calcium HR BMJ 2011;342:d2040doi: /bmj.d2040

39 Calcium + Vitamin D vs. Placebo n=20,090 No significant effect on all cause mortality BMJ 2011;342:d2040doi: /bmj.d2040

40 Effect of supplementation (Calcium +/- Vit D): Patient-level data (n=24,869) NNH = 240 NNH = 178 NNH = 283 Treating 1000 people with calcium or calcium + vitamin D x 5 years, would cause 6 additional MIs or stroke and prevent 3 fractures BMJ 2011;342:d2040doi: /bmj.d2040

41 Effect of supplementation: trial-level data (n=28,072) BMJ 2011;342:d2040doi: /bmj.d2040

42 BMJ 2013;346:f228 doi: /bmj.f228

43 Methodology Swedish mammography cohort, n=90,303 Cohort (n = 61,433) 1997 (n=38,984) Expanded dietary questionnaire Supplement questionnaire Categorized intake: <600mg mg reference range, RDA in Sweden 800mg mg >1400mg Follow-up (100%): Median 19 yrs (1,094,880 person yrs) Primary: death Secondary: CV disease, IHD, and stroke BMJ 2013;346:f228 doi: /bmj.f228

44 <600mg HR 1.38 ( ) >1400mg HR 1.40 ( ) <600mg HR 1.63( ) >1400mg HR 1.49 ( ) <600mg HR 1.65 ( ) >1400mg HR 2.14 ( ) <600mg HR 1.50 ( ) >1400mg HR 0.73 ( ) BMJ 2013;346:f228 doi: /bmj.f228

45 BMJ 2013;346:f228 doi: /bmj.f228

46 25% of cohort, 75% multivitamin (120mg calcium) (500mg) BMJ 2013;346:f228 doi: /bmj.f228

47 Conclusions High dietary intake of calcium is associated with increase in mortality and CV events High dietary intake + calcium tablets is associated with higher mortality Limitations: Cohort design Questionnaire reliability Healthy user bias BMJ 2013;346:f228 doi: /bmj.f228

48 JAMA Intern Med. doi: /jamainternmed

49 Methodology NIH-AARP diet and Health Study, US Age Men (n=219,059) Women (n=169,170) Baseline Dietary intake (quintiles) Frequency and dosage of calcium supplements Multivitamin intake An interaction by sex was found and therefore analysis was done separately Follow-up: 12 years 3,549,364 person-years JAMA Intern Med. doi: /jamainternmed

50 Results Calcium supplements: Men 23% Women 56% Multivitamins containing calcium Men 56% Women 58% JAMA Intern Med. doi: /jamainternmed

51 Dietary Calcium

52 Supplements Consistent when limited to calcium supplements and not multivitamins

53 Total Calcium Men CVD mortality RR 1.12 ( ) HD mortality RR 1.12 ( ) Women No association

54 Conclusions Supplementary calcium, but not dietary calcium is associated with increase CVD mortality in men, but not women. Limitations: Cohort design Duration of supplement use Calcium intake only measured at baseline

55 Key Points Multivitamins Limited data to support the routine use of multivitamins RCT data from healthy males indicated no benefit to supplementation Fish oils Limited data to support routine use in prevention of CV disease, both primary and secondary prevention Calcium Data remains inconclusive Minimal effect in fracture prevention unlikely to outweigh the potential risk of CV disease