Eur Heart J. 2014 Feb;35(6):353-64. doi: 10.1093/eurheartj/eht407. Epub 2013 Nov 27.
Combination pills containing aspirin, multiple blood pressure (BP) lowering drugs, and a statin have demonstrated safety, substantial risk factor reductions, and improved medication adherence in the prevention of cardiovascular disease (CVD). The individual medications in combination pills are already recommended for use together in secondary CVD prevention. Therefore, current information on their pharmacokinetics, impact on the risk factors, and tolerability should be sufficient to persuade regulators and clinicians to use fixed-dose combination pills in high-risk individuals, such as in secondary prevention. Long-term use of these medicines, in a polypill or otherwise, is expected to reduce CVD risk by at least 50-60% in such groups. This risk reduction needs confirmation in prospective randomized trials for populations for whom concomitant use of the medications is not currently recommended (e.g. primary prevention). Given their additive benefits, the combined estimated relative risk reduction (RRR) in CVD from both lifestyle modification and a combination pill is expected to be 70-80%. The first of several barriers to the widespread use of combination therapy in CVD prevention is physician reluctance to use combination pills. This reluctance may originate from the belief that lifestyle modification should take precedence, and that medications should be introduced one drug at a time, instead of regarding combination pills and lifestyle modification as complementary and additive. Second, widespread availability of combination pills is also impeded by the reluctance of large pharmaceutical companies to invest in development of novel co-formulations of generic (or 'mature') drugs. A business model based on 'mass approaches' to drug production, packaging, marketing, and distribution could make the combination pill available at an affordable price, while at the same time providing a viable profit for the manufacturers. A third barrier is regulatory approval for novel multidrug combination pills, as there are few precedents for the approval of combination products with four or more components for CVD. Acceptance of combination therapy in other settings suggests that with concerted efforts by academics, international health agencies, research funding bodies, governments, regulators, and pharmaceutical manufacturers, combination pills for prevention of CVD in those with disease or at high risk (e.g. those with multiple risk factors) can be made available worldwide at affordable prices. It is anticipated that widespread use of combination pills with lifestyle modifications can lead to substantial risk reductions (as much as an 80% estimated RRR) in CVD. Heath care systems need to deploy these strategies widely, effectively, and efficiently. If implemented, these strategies could avoid several millions of fatal and non-fatal CVD events every year worldwide.
含有阿司匹林、多种降压药物和他汀类药物的复方制剂已被证明在预防心血管疾病 (CVD) 方面具有安全性、显著降低风险因素和提高药物依从性。复方制剂中的各种药物已经被推荐用于二级 CVD 预防的联合使用。因此，关于其药代动力学、对危险因素的影响和耐受性的现有信息应该足以说服监管机构和临床医生在高危人群（如二级预防）中使用固定剂量复方制剂。长期使用这些药物，无论是在复方丸剂中还是其他形式，预计可使此类人群的 CVD 风险降低至少 50-60%。对于目前不建议同时使用这些药物的人群（例如一级预防），需要在前瞻性随机试验中证实这种风险降低。鉴于其附加益处，从生活方式改变和复方丸剂两方面综合估计，CVD 的联合相对风险降低（RRR）预计为 70-80%。CVD 预防中广泛使用联合治疗的第一个障碍是医生不愿意使用复方制剂。这种不情愿可能源于这样一种信念，即生活方式改变应优先考虑，药物应一次引入一种，而不是将复方制剂和生活方式改变视为互补和附加的。其次，大型制药公司不愿意投资开发通用（或“成熟”）药物的新型联合制剂，也阻碍了复方制剂的广泛应用。基于“大规模方法”的药物生产、包装、营销和分销的商业模式可以使复方丸剂以负担得起的价格提供，同时为制造商提供可行的利润。第三个障碍是新型多药物复方制剂的监管批准，因为对于批准用于 CVD 的四种或更多成分的组合产品，几乎没有先例。在其他情况下接受联合治疗表明，通过学术界、国际卫生机构、研究资助机构、政府、监管机构和制药制造商的共同努力，可以以负担得起的价格在全球范围内提供用于预防 CVD 的复方制剂，适用于患有疾病或处于高风险的人群（例如，有多重风险因素的人群）。预计广泛使用复方制剂结合生活方式改变可以使 CVD 的风险降低幅度相当大（估计的 RRR 高达 80%）。医疗保健系统需要广泛、有效和高效地部署这些策略。如果实施这些策略，每年可以避免全世界数百万人因 CVD 导致的致命和非致命事件。
