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? 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.

Multivitamins in the Prevention of Cardiovascular Disease in Men 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= 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？ 其研究結論是否可應用在我們的病患身上？ 經濟效益評估 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 !