Angeli Fabio, Reboldi Gianpaolo, Mazzotta Giovanni, Garofoli Marta, Ramundo Elisa, Poltronieri Cristina, Verdecchia Paolo
Section of Cardiology, Hospital Media Valle del Tevere, Umbria, Perugia, Italy.
High Blood Press Cardiovasc Prev. 2012 Jun 1;19(2):51-4. doi: 10.1007/BF03262453.
The goal of antihypertensive therapy is to reduce the risk associated with blood pressure elevation. Although the choice of first-line drug therapy may exert some effects on different long-term cardiovascular endpoints, randomized clinical trials and meta-analyses demonstrated that blood pressure reduction per se is the primary determinant in primary and secondary prevention. Numerous analyses carried out over the last years have repeatedly shown that many patients require the combination of two or more drugs to reach the recommended level of blood pressure control. Within this context, combination therapy with separate agents or fixed-dose combination pills offers an attractive ability to lower blood pressure more quickly, decrease adverse effects and reach blood pressure target. It is not clear whether fixed combinations of antihypertensive agents in a single tablet provide a greater benefit than the corresponding components given separately. In other words, it is not clear if the use of fixed combinations translates into a clearly improved blood pressure control and cardiovascular prevention in clinical practice. Fixed-dose combinations may simplify the treatment regimen by reducing the number of pills and may be attractive for many hypertensive patients. However, single-pill (fixed) drug combinations have some disadvantages: (i) branded fixed combinations may be more expensive than equivalent free combinations; (ii) the duration of action of individual components may not be equivalent, and this may not justify a single daily dosing of the combination; and (iii) the use of fixed combinations implies less flexibility in modifying the doses of individual components and the exposure of patients to unnecessary therapy. Moreover, should a patient develop side effects to one component, the entire combination should be discontinued and replaced by free drugs. The following three types of fixed-dose tablets have been recently proposed to give additional flexibility: (i) tablet manufactured so that each of the two drugs is placed at opposite ends of the tablet with a drug-free (inactive) layer placed in between; (ii) tablet with the combination of drugs at each end with the inactive zone in between; and (iii) tablet divided into discrete, separate segments (the two drugs are combined uniformly), which provides benefits for initial close titration and dosage adjustments. Currently, none of the fixed-dose tablets available on the market have these characteristics and, consequently, are unable to be broken to allow sufficient flexibility.
抗高血压治疗的目标是降低与血压升高相关的风险。尽管一线药物治疗的选择可能会对不同的长期心血管终点产生一些影响，但随机临床试验和荟萃分析表明，血压降低本身是一级和二级预防的主要决定因素。过去几年进行的大量分析反复表明，许多患者需要联合使用两种或更多药物才能达到推荐的血压控制水平。在此背景下，联合使用单独的药物或固定剂量复方药丸具有更快速降低血压、减少不良反应并达到血压目标的诱人能力。尚不清楚单片复方抗高血压药物是否比单独使用相应成分带来更大益处。换句话说，尚不清楚在临床实践中使用固定复方制剂是否能明显改善血压控制和心血管疾病预防。固定剂量复方制剂可通过减少药片数量简化治疗方案，对许多高血压患者可能具有吸引力。然而，单片（固定）药物复方制剂存在一些缺点：（i）品牌固定复方制剂可能比等效的自由组合更昂贵；（ii）各成分的作用持续时间可能不等效，这可能无法证明该复方制剂每日单次给药的合理性；（iii）使用固定复方制剂意味着在调整各成分剂量方面灵活性较小，且患者会接受不必要的治疗。此外，如果患者对其中一种成分出现副作用，应停用整个复方制剂，改用自由组合的药物。最近有人提出以下三种类型的固定剂量片剂以增加灵活性：（i）制成的片剂，使两种药物分别置于片剂的两端，中间有一层无药（惰性）层；（ii）两端为药物组合、中间为惰性区的片剂；（iii）分成离散、独立部分（两种药物均匀混合）的片剂，这有利于初始的精确滴定和剂量调整。目前市场上没有一种固定剂量片剂具有这些特性，因此无法掰开以提供足够的灵活性。
