實證醫學專題報告
服用綜合維他命，未來發生心
血管疾病的機率有多少?
報告者：Intern 張邦彥 潘泊諺
指導者：王啟忠 主任
門諾醫院 家醫科 March 12th, 2013
情境
• 王先生今年 62 歲，高血壓已服藥 (CCB)
將近 10 年，血壓控制良好。體重過重
(BMI:26)，是個老菸槍，常常咳嗽有濃
痰。
• 王先生年過60歲，開始擔心身體狀況，
他想知道每天服用綜合維他命，自己
未來發生心血管疾病的機率有多少？
問題形成
• 病人：服用綜合維他命，未來發生心血管疾病
的機率
• 介入或暴露 ： 服用綜合維他命
• 比較：沒有服用綜合維他命
• 臨床結果：心血管疾病的發病率及死亡率
• 這是關於 「治療」的問題
文獻搜尋
• 關鍵字 : multivitamin, cardiovascular disease, men
• 資料庫 : PubMed, ACP journal club
• 優先順序 : Systematic review/Meta-analysis >RCT>…
The Oxford 2011 Levels of Evidence
Systematic review
Meta-analysis
RCT
ACP journal club
文獻評讀
1. 病人的治療分派是隨機的嗎？
YES!
• A total of 14641 men were randomized and
stratified by age, prior diagnosis of cancer,
prior diagnosis of CVD, etc.
2. 對照組與實驗組在進
入試驗時是否相似？
YES!
3. 病人、醫生、研究者是否對治療不知情？
YES!
• The PHS II was a randomized, double-blind,
placebo-controlled trial evaluating the balance
of risks and benefits of a multivitamin
(Centrum Silver or placebo daily).
4. 病人的追蹤是否夠久、夠充足完整？
YES!
• The trial began in 1997 with continued treatment
and follow-up through June 1, 2011(a mean of
11.2 years of treatment and follow-up in 14 641
men)
• Morbidity and mortality follow-up in PHS II were
high—98.2% and 99.9%, respectively. In addition,
morbidity and mortality follow-up as a
percentage of person-time each exceeded 99.9%.
5. 是否所有的病人都被放到原先分派的組別
中做分析？
YES!
• All primary analyses were based on the
intention-to-treat principle.
6. 所有組別是否被平等對待？
Yes!
• Every 6 months for the first year, then
annually thereafter, PHS II participants were
sent monthly calendar packs containing a
multivitamin or placebo.
• Annual mailed questionnaires asked about
adherence, adverse events, end points, and
risk factors.
文獻評讀之效度/信度
Multivitamins in the Prevention
of Cardiovascular Disease in Men
JAMA, November 7, 2012
病人的治療分派是隨機
○
對照組與實驗組在進入試
驗時相似
○
病人、醫生、研究者對治
療不知情
○
病人的追蹤夠久、夠充足
完整
○
所有的病人都被放到原先
分派的組別中做分析
○
所有組別被平等對待
○
研究結果
• During a median follow-up of 11.2 (interquartile
range, 10.7-13.3) years, there were 1732
confirmed major cardiovascular events.
• There was no significant effect of a daily
multivitamin on major cardiovascular events.
• A daily multivitamin had no effect on total MI,
total stroke, or CVD mortality.
• A daily multivitamin was also not significantly
associated with total mortality.
Hazard Ratio(風險比值) ：
是被用來比較兩組的“發生事件所需時間 (time to event)”
，即是介入組死亡的風險除以對照組死亡的風險。
There were no significant difference in major
cardiovascular events, total MI, total stroke
between cumulative incidence curves.
Cumulative incidence rate：某世代族群或某固定族
群的人，經過某段觀察時間後，發生某事件﹙疾
病﹚的人口佔該世代族群人口總數的百分比。
• No significant interaction by baseline CVD history
status (P=.62 for interaction) for primary (HR,
1.02; 95% CI, 0.92-1.13) vs secondary (HR, 0.96;
95% CI, 0.75-1.22) prevention.
• The cumulative incidence curves did not differ for
primary (crude log-rank P=.71) or secondary
(crude log-rank P=.94) prevention during up to 14
years of treatment and follow-up.
• 對CVD的初級預防和次級預防都無顯著效果
Potential Adverse Effects
• No significant effects on gastrointestinal tract
symptoms (peptic ulcer, constipation, diarrhea,
gastritis, and nausea), fatigue, drowsiness, skin
discoloration, and migraine (P=.05 for all).
• Participants taking the multivitamin vs placebo
were more likely to have skin rashes (2125 in the
multivitamin group and 2002 in the placebo
group; HR, 1.07; 95% CI, 1.01-1.14; P=.03).
研究結論
• 在超過十年的治療和追蹤下，服用綜合維
他命並無法讓這群美國男性醫師降低心血
管疾病、心肌梗塞、中風的發生率，以及
心血管疾病的死亡率。
回到我們的病患身上
• 病人性質與治療方式是否與我們的病患條件
一致？
–
–
–
–
種族
職業
年齡
本身潛在的疾病
• 其研究結論是否可應用在我們的病患身上？
• 經濟效益評估
自我評估
•
•
•
•
•
是否提出一個可以回答的問題？
是否能從廣大資料來源中找到有用的證據？
是否知道現有的最佳證據來源？
是否能審慎評讀證據的正確性？
是否能整合證據與病患的價值觀？
謝謝大家 !