Hypertension: treatment with combined preparations

In recent years, the United States is increasing the availability and frequency of use of preparations of a combination of two antihypertensive drugs, which can be used as first-line treatment of hypertension. It is considered that due to the multifactorial pathogenesis of essential hypertension is justified by pharmacological intervention in the two different systems, the height adjustment of blood pressure.

There are grounds to believe that the use of preparations containing two drugs with different mechanisms of action leads to both improve cooperation with your doctor patient therapy of hypertension and increases the tolerance of the drug by the patient.

The current recommendations of the European Society of Hypertension and the European Society of Cardiology (ESH / ESC) of 2007 emphasize the importance of proper mating of antihypertensive drugs when monotherapy fails. According to the guidelines, antihypertensive treatment can also be initiated from the application of the two drugs in small doses or dose combination, which is a combination of small doses of two antihypertensive drugs with different mechanisms of action. This applies especially to patients with significantly elevated blood pressure (hypertension moderate or severe) or with high or very high risk of cardiovascular complications.

By 2007, there were no large studies evaluating the efficacy and benefits of initiating combination therapy based on two antihypertensive drugs. In September 2007, the published results of the ADVANCE (Action in Diabetes and Vascular Disease), which demonstrated the benefits of combination product based on angiotensin-converting enzyme inhibitor (perindopril) and a diuretic tiazydopodobnym (indapamide) in patients with type 2 diabetes at the turn March and April 2008, during the convention of the American College of Cardiology in Chicago announced, in turn, results of the program known by the acronym ACCOMPLISH (Avoiding Cardiovascular events thorugh Combination therapy in Patients Living with Systolic Hypertension).

The ACCOMPLISH study is the first large clinical program in which there is used a traditional schedule treatment of hypertension, i.e. the start of treatment from one antihypertensive drug and antihypertensive drugs include the following. In this study, treatment was initiated as a combined preparation, which is a combination of two antihypertensive drugs. The aim of the study was to demonstrate whether treatment dose combination of an ACE inhibitor and a calcium antagonist compared to treatment dose combination of an ACE inhibitor and a thiazide diuretic is beneficial in terms of reducing the incidence of cardiovascular events.

The study included 11 446 men and women aged 55 years and older with hypertension and diagnosed cardiovascular or chronic kidney disease or target organ damage from hypertension. At the time of enrollment only 37.5 percent of patients with high blood pressure were well controlled.

Men accounted for about 60 percent of the study population, patients aged 70 years or more – about 41 percent in the study group. Type 2 diabetes was present in 60 percent of patients, obesity, half of the patients, almost all patients (97 percent) previously received antihypertensive drugs, three-quarters of patients received at least two such drugs.

Patients were randomly assigned to two groups: one received treatment on the formulation consisting of benazepril 20 mg (Losartan) and Amlodipine 5 mg, in the second – on the formulation consisting of benazepril hydrochloride (20 mg) and hydrochlorothiazide (12.5 mg). In case of failure to achieve target blood pressure (<140/90 mm Hg or <130/80 mm Hg in patients with diabetes or renal failure) after a month of observation doubled dose of benazepril in the preparation used. If after a month of blood pressure is still not has been reduced to the target values, doubled dose of the second drug in the formulation. After another month in the case of treatment failure was attached to an open other drugs (beta-blockers, alpha-blockers, clonidine, or loop diuretic). Main composite endpoint evaluated the incidence of total cardiovascular events – death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, coronary revascularization, or cardiac arrest with successful resuscitation. The study was conducted in the United States and in Europe (Denmark, Finland, Norway and Sweden).

Advantageous results in 80 percent of patients

This study was terminated prematurely due to the achievement of the study protocol significant differences in the incidence of cardiovascular events between the compared groups. Average follow-up was 39 months. During the study achieved target blood pressure in 80 per cent. patients. Half of the patients in both groups received only one dose combination tablet. In the group treated with benazepril and amlodipine blood pressure values ​​were higher than in the group treated with benazepril and hydrochlorothiazide. In the 30 month study, this difference was systolic 0.7 mm Hg.

In the analysis of the frequency of cardiovascular events has been demonstrated that the incidence of the primary endpoint decreased significantly by 20 percent. the group treated with benazepril and amlodipine compared with those treated with benazepril and hydrochlorothiazide. For evaluated separately components of the primary endpoint showed a comparable trend to reduce the incidence of events. It was also a significant reduction in the incidence (20 percent). Assessed total deaths from cardiovascular causes and nonfatal heart attacks and strokes in patients treated with amlodipine and benazepril, compared with those treated with hydrochlorothiazide and benazepril.

In conclusion, this study, the authors concluded that the results could affect the applicable recommendations in the United States JNC 7 Report, in which thiazide diuretics play a fundamental role in initiating treatment of hypertension.

The results will no doubt impact on the management of patients with hypertension. Expand our knowledge of the complex preparations for the treatment of hypertension. As demonstrated in this study, the use of combined preparations may be associated with improved blood pressure control and obtaining the target values ​​in the higher percentage of patients. The exact interpretation of the results of ACCOMPLISH will be possible after the publication of the full results.