Simonyi Gábor, Ferenci Tamás
Szent Imre Egyetemi Oktatókórház Anyagcsere Központ Budapest Tétényi út 12-16. 1115.
Óbudai Egyetem, Neumann János Informatikai Kar Élettani Szabályozások Csoport Budapest.
Orv Hetil. 2014 Nov 23;155(47):1882-8. doi: 10.1556/OH.2014.30037.
Adequate patient adherence has outstanding importance during the management of chronic disorders including hypertension. In particular, target blood pressure and reduction of cardiovascular risk can be reached only by prolonged, effective pharmacotherapy. Hypertension is known as one of the most significant cardiovascular risk factors. According to international data, antihypertensive therapy with a fixed combination improves patient adherence by about 20 per cent in comparison with free combinations.
The aim of the study was to evaluate the persistence on one-year treatment with the free or fixed combination of ramipril and amlodipine, administered for the indication of hypertension.
Information from the National Health Insurance Found prescriptions database, on pharmacy-claims between October 1, 2012 and September 30, 2013 was analyzed. The authors identified patients who filled prescriptions for fixed or free combinations of ramipril and amlodipine, prescribed for the first time, for the therapeutic indication of hypertension. The subjects have not received antihypertensive therapy with similar active substances during the year preceding the study. Using the Kaplan-Meier technique, the authors constructed persistence curves with a 95% confidence interval for point estimates calculated on a log scale. Patients who were still persistent at the closing date of the study were considered censored. For modeling of the curves, the authors used semi-parametric Cox's regression where antihypertensive therapy was the only (categorical) explanatory variable, and the patients taking the fixed combination were regarded as the reference group.
During the study period, combination antihypertensive therapy with ramipril and amlodipine was started with a free or a fixed combination of these agents in 20,096 and 10,449 patients, respectively. One-year persistence rate in patients taking ramipril and amlodipine as a free combination was 34%, whereas 54% in those on the fixed combination. This 20 percent difference means that the rate of persistence was higher by 58.8/2%. Considering only the 360-day study period, the mean duration of persistence was 272 days in patients on the fixed, and 206 days in those taking the free combination. Analyzing persistence on treatment with these combinations showed that the actual rate of discontinuation was about twice higher during treatment with the free, compared with the use of the fixed combination (hazard ratio = 1.94, p<0.001).
This study, which is unique even by international standards, demonstrated the clear benefit of initiating antihypertensive therapy with the fixed combination of ramipril and amlodipine over starting treatment with the free combination. In particular, the chance of discontinuation during a one-year treatment with the former was approximately half of that seen with the latter. Inadequately controlled hypertension is a significant cardiovascular risk factor. The markedly higher persistence of patients on therapy with the fixed combination of ramipril and amlodipine can lead to a reduction in cardiovascular risk, which might prove - on the longer term - a positive outcome of public health significance.
在包括高血压在内的慢性疾病管理过程中，患者的充分依从性至关重要。特别是，只有通过长期有效的药物治疗才能达到目标血压并降低心血管风险。高血压是最重要的心血管危险因素之一。根据国际数据，与自由联合用药相比，固定复方降压治疗可使患者依从性提高约20%。
本研究旨在评估雷米普利和氨氯地平自由联合或固定联合用于高血压治疗时患者一年治疗期的持续性。
分析了国家健康保险基金处方数据库中2012年10月1日至2013年9月30日期间的药房报销信息。作者确定了首次开具雷米普利和氨氯地平固定或自由联合用药处方用于高血压治疗的患者。在研究前一年，这些受试者未接受过含有相似活性成分的降压治疗。作者采用Kaplan-Meier技术构建了持续性曲线，并计算了对数尺度上点估计值的95%置信区间。在研究结束日期仍持续用药的患者被视为截尾。为了对曲线进行建模，作者使用了半参数Cox回归，其中降压治疗是唯一的（分类）解释变量，服用固定联合用药的患者被视为参照组。
在研究期间，分别有20,096例和10,449例患者开始接受雷米普利和氨氯地平自由联合或固定联合的复方降压治疗。雷米普利和氨氯地平自由联合用药患者的一年持续性率为34%，而固定联合用药患者为54%。这20%的差异意味着持续性率高出58.8/2%。仅考虑360天的研究期，固定联合用药患者的平均持续时间为272天，自由联合用药患者为206天。对这些联合用药治疗的持续性分析表明，与固定联合用药相比，自由联合用药治疗期间实际停药率约高出两倍（风险比=1.94，p<0.001）。
即使按照国际标准，本研究也是独特的，它证明了雷米普利和氨氯地平固定联合启动降压治疗比自由联合启动治疗具有明显优势。特别是，前者一年治疗期间停药的可能性约为后者的一半。高血压控制不佳是一个重要的心血管危险因素。雷米普利和氨氯地平固定联合治疗患者的持续性显著更高，这可能会降低心血管风险，从长远来看，这可能会带来具有公共卫生意义的积极结果。
