[Medication adherence with the fixed combination of ramipril and amlodipine].
BACKGROUND
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.


OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Szent Imre Egyetemi Oktatókórház Anyagcsere Központ Budapest Tétényi út 12-16. 1115.
Gábor
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Simonyi
Óbudai Egyetem, Neumann János Informatikai Kar Élettani Szabályozások Csoport Budapest.
Tamás
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Ferenci
D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D016208:Databases, Factual; D004334:Drug Administration Schedule; D004338:Drug Combinations; D011307:Drug Prescriptions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006814:Hungary; D006973:Hypertension / Q000188:drug therapy*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D017257:Ramipril / Q000008:administration & dosage*; D016903:Drug Monitoring
D000959:Antihypertensive Agents; D004338:Drug Combinations; D017311:Amlodipine; D017257:Ramipril
adherence; adherencia; antihipertenzív terápia; antihypertensive therapy; combination of ramipril and amlodipine; persistence; perzisztencia; ramipril/amlodipin kombináció