作者：Laurie Barclay, MD 齣處：WebMD醫學新聞 　　December 10, 2009 — 根據綫上發錶於11月23日循環(Circulation)期刊的研究結果 抽菸依舊是心 抽菸是心髒病成人患者的主要死亡風險因素 - 趣味新聞網

發表日期 2009-12-26T08:05:19+08:00

     作者：Laurie Barclay, MD
齣處：WebMD醫學新聞

December 10, 2009 — 根據綫上發錶於11月23日循環(Circulation)期刊的研究結果，抽菸依舊是心髒病成人患者以及有心髒病且使用clopidogrel這項藥物之癌癥成人患者的主要死亡風險因素。

紐約市紐約大學醫學院的Jeffrey S. Berger醫師以及「Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA)」研究之研究人員寫道，在體外血小闆功能檢測中，抽菸會增加血小闆凝集力，以及clopidogrel的血小闆抑製程度。抽菸情況是否會影響clopidogrel和臨床結果的關聯還未知。

使用CHARISMA研究中確定有心血管疾病之12,152名參與者的資料，研究者檢視抽菸狀態和使用clopidogrel治療對於各種原因死亡、心血管原因死亡、癌癥死亡風險的影響。抽菸狀態分類為目前有抽菸者、曾經抽菸者、未曾抽菸者。

相較於未曾抽菸者，目前有抽菸者和各種原因死亡率增加有關(校正風險比[HR]為2.58；95%信心區間[CI]為1.85 - 3.60)，同樣的，心血管死亡率(HR為2.26；95% CI為1.48 - 3.45)以及癌癥死亡率(HR為4.16；95% CI為2.46 - 7.03)也是。

抽菸狀態會影響clopidogrel對於死亡率的效果(對於目前有抽菸者，交互作用P值= .018)。Clopidogrel與減少目前有抽菸者的各種原因死亡率有關(HR為0.68；95% CI為0.49 - 0.94)，不過，對於曾經抽菸者(HR為0.95；95% CI為0.75 - 1.19)或未曾抽菸者(HR為1.14；95% CI為0.83 - 1.58)，clopidogrel並不會降低各種原因死亡率。

心血管死亡率的模式類似。一如預期，clopidogrel和癌癥死亡率在各種抽菸狀態並無明顯關係。抽菸狀態會影響齣血風險，目前有抽菸者中，隨機分派接受clopidogrel的病患，嚴重或中度齣血的風險顯著增加(HR為1.62；P =.04)，不過，未曾抽菸者中，增加的風險小且不顯著(HR為1.31；P = .15)。

研究作者寫道，使用Clopidogrel治療對於目前抽菸者最有效，但是嚴重齣血風險也高於未曾抽菸者，需要後續研究來探討此一可能性。

研究限製包括，使用事後次組分析，抽菸狀態的分析僅根據一次調查，但是研究對象在研究期間可能改變抽菸習慣。

研究作者結論錶示，確定有心血管疾病的患者中，目前有抽菸者的各種原因死亡、心血管原因死亡和癌癥死亡風險、以及嚴重或中度齣血風險都增加。這些資料認為，clopidogrel的風險和利益會受到抽菸狀態影響，需要更多證據來支持「clopidogrel的抗血小闆效果在目前有抽菸者會加強」的這項假設

Sanofi-Aventis與Bristol-Myers Squibb資助CHARISMA試驗。部份研究作者與國傢心髒肺髒與血液研究中心、美國心髒協會、AstraZeneca、The Medicines Company、Bristol-Myers Squibb、Eisai、Ethicon、 Heartscape、Sanofi-Aventis、Arena、Astellas、Bayer、Cardax、Centocor、Cogentus、Daiichi-Sankyo、Eli Lilly、GlaxoSmithKline、Johnson & Johnson、McNeil、Medtronic、Millennium、Molecular Insights、Otsuka、Paringenix、PDL、Philips、Portola、Schering-Plough、Takeda、Vertex、Boehringer-Ingelheim、Endotis、MSD、Nycomed、Servier、Scios、Guerbet Medical、Boston Scientific、Cordis、Stago、Fondation de France、INSERM、Federation Francaise de Cardiologie、Societe Francaise de Cardiologie、PlaCor和/或Accumetrics等有各種財務關係。

Circulation. 綫上發錶於2009年11月23日。


Smoking Major Risk Factor for Mortality in Adults Treated for Heart Disease

By Laurie Barclay, MD
Medscape Medical News

December 10, 2009 — Smoking persists as a major risk factor for mortality from heart disease and cancer in adults who already have heart disease and receive clopidogrel, according to the results of a study reported online in the November 23 issue of Circulation.

"Smoking increases platelet aggregability and the degree of platelet inhibition by clopidogrel on ex vivo platelet function tests," write Jeffrey S. Berger, MD, MS, from the New York University School of Medicine, New York City, and colleagues from the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) Investigators. "Whether smoking status affects the relationship between clopidogrel and clinical outcomes is unknown."

Using a group of 12,152 participants with established cardiovascular disease who were enrolled in CHARISMA, the investigators examined the association between smoking status and treatment with clopidogrel on the risk for all-cause, cardiovascular, and cancer mortality. Smoking status was characterized as current smoker, former smoker, or never smoker.

Compared with never smoking, current smoking was associated with increases in all-cause mortality (adjusted hazard ratio [HR], 2.58; 95% confidence interval [CI], 1.85 - 3.60), as well as in cardiovascular mortality (HR, 2.26; 95% CI, 1.48 - 3.45) and cancer mortality (HR, 4.16; 95% CI, 2.46 - 7.03).

Smoking status affected the effect of clopidogrel on mortality (P for interaction = .018 for current smokers). Clopidogrel was associated with a reduction in all-cause mortality among current smokers (HR, 0.68; 95% CI, 0.49 - 0.94). However, clopidogrel treatment was not associated with lower all-cause mortality among former smokers (HR, 0.95; 95% CI, 0.75 - 1.19) or never-smokers (HR, 1.14; 95% CI, 0.83 - 1.58).

Cardiovascular mortality showed a similar pattern. As anticipated, there was no apparent relationship between clopidogrel and cancer mortality by smoking status. Smoking status did appear to affect the risk of bleeding. Among current smokers, patients randomly assigned to receive clopidogrel had a significantly increased risk of severe or moderate bleeding (HR, 1.62; P =.04). However, this increased risk was smaller and nonsignificant among never-smokers (HR, 1.31; P = .15).

"Clopidogrel therapy may be more effective in current smokers, but it may also confer a greater bleeding risk than in non-smokers," the study authors write. "Further studies are needed to investigate this possibility."

Limitations of this study include use of post hoc subgroup analysis and analyses of smoking status based on a single determination that may have changed during the study period.

"Among patients with established cardiovascular disease, current smokers are at increased risk for all-cause, cardiovascular, and cancer-specific mortality, cardiovascular events, and severe or moderate bleeding," the study authors conclude. "These data also suggest that the benefit and risk of clopidogrel may be modified by smoking status, thus providing additional evidence to support the hypothesis that the antiplatelet effect of clopidogrel may be enhanced in current smokers."

The CHARISMA trial was funded by Sanofi-Aventis and Bristol-Myers Squibb. Some of the study authors report various financial relationships with the National Heart, Lung, and Blood Institute, the American Heart Association, AstraZeneca, The Medicines Company, Bristol-Myers Squibb, Eisai, Ethicon, Heartscape, Sanofi-Aventis, Arena, Astellas, Bayer, Cardax, Centocor, Cogentus, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, McNeil, Medtronic, Millennium, Molecular Insights, Otsuka, Paringenix, PDL, Philips, Portola, Schering-Plough, Takeda, Vertex, Boehringer-Ingelheim, Endotis, MSD, Nycomed, Servier, Scios, Guerbet Medical, Boston Scientific, Cordis, Stago, Fondation de France, INSERM, Federation Francaise de Cardiologie, Societe Francaise de Cardiologie, PlaCor, and/or Accumetrics.

Circulation. Published online November 23, 2009.

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