在发达国家心血管疾病(Cardiovascular disease ,CVD)位居死亡原因之首。为延缓或预防此类疾病的发生,人们已采用了诸如调整生活方式,药物治疗,经皮或手术治疗等一系列预防措施。现有的预防心血管疾病,如缺血性心脏病(ischemic heart disease ,IHD)和脑血管意外(cerebrovascular accidents ,CVA)的药物均是针对单一危险因子而设计的。
本报道是一项根据目前可获取的既往研究资料所进行的,关于降低4项独立危险因子( 低密度脂蛋胆固醇LDL-C,血压, 同型半胱氨酸和血小板抑制)的作用及其对CVD预防的假定效益的非常有趣的统计分析。
目的
评价含6种不同成分的单一配方("Polypill")降低4项CVD危险因子的可能效应。
研究设计
以一系列已发表的评估降低4项危险因子中每一项因子疗效的随机试验和队列研究的荟萃分析为基础,作者选择了治疗或调整不同危险因子的药物或维生素:即LDL-C(他汀),高血压(噻嗪类,b受体阻滞剂,血管紧张素转换酶抑制剂,血管紧张素II受体拮抗剂及钙拮抗剂)同型半胱氨酸(叶酸)和血小板功能(低剂量阿司匹林)。
计算既往没有CVD,从 55岁开始应用Polypill改变这4项危险因子对IHD和卒中发生的联合效应。
结果
图1显示了55~64岁的患者应用Polypill治疗2年对IHD和卒中风险的预期效应。 本分析表明, 应用Polypill可使LDL-C降低70 mg/dl,舒张压下降11 mmHg,血浆同型半胱氨酸减少3 mmol/L。其联合效应将使IHD事件的风险减少88% (95% CI: 84~91), 卒中风险减少80% (95% CI: 71~87)。
(图1:与Polypill相关的IHD及卒中风险下降)
图2显示由55岁开始服用Polypill 后预期避免IHD事件和卒中发生的比例。图3描述了获益人群额外获得的无IHD事件或卒中生存的年数。总体而言,35位男性或女性将获益,得到11年无事件生存时间。
(图2:服用Polypill后,避免发生IHD事件和卒中的人数比例)
药物治疗显然有副作用。从构成Polypill 的6种成分看,阿司匹林最容易发生可导致停药的严重副作用。本研究显示, 3.9%的患者报告与阿司匹林有关的症状, 但只有1.6%的人因副作用而停止治疗。而仅有< 0.1%的患者因为与Polypill的其他成分有关的症状而停药。
(图3:获得无IHD事件或卒中生存的年数)
结论
研究者们的结论认为,每天服用1粒包含6种特定成分的Polypill策略可预防88%的心脏事件和80%的卒中。约3人中即有1人直接获益,每人平均可获得11~12年的无心脏事件或无卒中生存 (对55~64岁的人而言,则为20年)。
评注
一次在冠心病监护病房早查房时,我第一次听说Polypill。我的一个病人问我能否给他开些Polypill 。我不知道他指的是什么,所以问道:“什么样的Polypill”?这个病人随即给我看了一张有大大标题的早报,上面说一种新药可减少80%的心脏疾病。
毫无疑问本研究是一项非常有趣的统计分析,但有可行性吗?是否有可能在一个药丸中混合这么多组份?应该用哪些特定药物?使用的剂量如何?可能的组合是如此之多。期望的心血管疾病预防效应是否和理论预测一样好?尽管作者在分析中也提到不同成分的副作用, 我想知道联合用药是否真的不会导致严重副作用加倍出现?我也很关心副作用的监控问题,尽管作者们仅是简单带过。
确切地说这是有趣的,发人深省的,挑战性的,还是令人困惑的? 最有可能这仅是一种理想状态。
British Medical Journal. 2003;326(7404):1419
A Strategy to Reduce Cardiovascular Disease by More Than 80%
Cardiovascular disease (CVD) is the number 1 cause of mortality in developed countries. A series of preventive measures such as lifestyle modifications, drug treatments, and percutaneous and surgical procedures have been smartly developed with the idea of delaying or preventing the disease. Drug treatments have been designed to prevent cardiovascular diseases, such as ischemic heart disease (IHD) and cerebrovascular accidents (CVA) by targeting single risk factors.
The present report is a very interesting statistical analysis based on current available knowledge (gathered from previous studies) on the impact of reducing 4 independent risk factors (low density lipoprotein [LDL] cholesterol, blood pressure, homocysteine and platelet inhibition) and their presumed effect on CVD prevention.
Aim
To assess the probable effect of lowering 4 CVD risk factors with 6 different components in a single formulation ("Polypill").
Study Design
Based on a series of published meta-analysis of randomized trials and cohort studies that evaluated the effects of lowering each 1 of the 4 risk factors, the authors identified drugs or vitamins used to treat or modify LDL cholesterol (statins), hypertension (thiazides, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and calcium channel blockers), homocysteine (folic acid), and platelet function (low dose aspirin).
The combined effect of changing these 4 risk factors on IHD and stroke if people without previous CVD used the Polypill from age 55 was calculated.
Results
Figure 1 shows the proposed effects of the Polypill on the risks of IHD and stroke after 2 years of treatment in patients aged 55-64 years. According to the analysis, use of the Polypill would reduce LDL cholesterol by 70 mg/dL, diastolic blood pressure by 11 mm Hg, and serum homocysteine by 3 mcmol/L. The combined effect would be an 88% reduction (95% CI: 84-91) in the risk of an IHD event and 80% reduction (95% CI: 71-87) in risk of stroke.
(Figure 1:Risk reduction of IHD and stroke associated with Polypill.)
Figure 2 shows the expected proportion of people who would avoid an IHD event and stroke by taking the Polypill from age 55. Figure 3 depicts the number of years of life gained without an IHD event or stroke in those who benefit. In general, 35 men or women will benefit and will gain 11 years without any event.
(Figure 2:Proportion of people who would avoid an IHD event and stroke by taking Polypill.)
Obviously, drug treatment is also associated with side effects. From all the 6 components that would make up the Polypill, aspirin is the one with more serious side effects sufficient to stop taking the tablets. In the present study, 3.9% of the patients would report a symptom attributable to aspirin and only 1.6% would stop treatment due to this side effect, whereas < 0.1% of patients would stop treatment due to a symptom attributable to any of the other components of the Polypill.
(Figure 3:Number of years of life gained without an IHD event or stroke)
Conclusions
Investigators concluded that the Polypill strategy based on a single daily pill containing 6 components as specified would prevent 88% of heart