• Fixed-dose combinations – the promising choice in arterial hypertension therapy

    June 1, 2015

    Arterial hypertension (AH) is the most common cardiovascular disease. It is the most common cause of morbidity and mortality worldwide every year. Hypertension is the main cause of cardiovascular disease (CVD) and mortality worldwide. Although scientists and doctors have made significant efforts to control blood pressure and have great achievements in this direction, there still remains a long way to go towards optimizing blood pressure control in terms of clinical practice. Statistics show that only a small proportion of hypertensive patients can reach rational levels of BP through monotherapy, while most patients need combination therapy to control their disease.

    A study of trends in the use of antihypertensive drugs in France for the period 2002 – 2012 supported the view that the requirements of fixed dose combinations have increased from 19% to 30%. Combination therapies may combine two or more drugs which are applied separately or in a fixed dose, where the second option seems to be more popular in clinical practice, based on the benefits in terms of convenience, cost, efficiency and side effects.

    Monotherapy vs. combination therapy

    Several clinical studies have shown that most patients with hypertension are unlikely to have their blood pressure normalized using a single drug for a fairly long period of time. Therefore, physicians tend to give a higher dose at the beginning, although high-dose therapy typically only results in a modest antihypertensive effect, accompanied with some severe side effects, and this type of therapy supports the perspective that the patient cannot receive further higher doses because the medicine cannot meet their needs for the recommended dose.

    Fixed dose combinations (FDC)
    When monotherapy is replaced with a fixed-dose combination, it is natural for the patient to ask whether the fixed dose could offer sufficient benefits which justify the switch from traditional monotherapy. FDC as a promising option for patients with hypertension may have some potential advantages, as it will become clear below.

    First, the combination of various medicinal agents in the fixed dose can produce some surprising effects (in a positive sense) in patients when compared with the use of each combination component separately. In a perfect combination, FDC provide a synergistic effect. When combining medicines from different classes their effects occur based on their diverse action mechanisms and temporal scope. Fixed-dose combinations in hypertension have the potential for long-term action. Clinical studies have demonstrated that angiotensin ΙΙ receptor blockers (ARB) may reduce peripheral edema caused by calcium channel blockers, which is in line with the idea that a combination of two antihypertensive agents of different classes in one formulation can compensate for the adverse effects of each one separately in many cases. Furthermore, any side effects of the medicines in the combination may also be reduced due to the low doses.

    Second, there is a psychological problem that the treatment of chronic disease has to be taken into account. Since most patients with hypertension are older, have poor memory and often experience a difficulty in moving around, the convenience and the ease of compliance with the prescribed therapies are of special importance. Meta-analysis has shown that fixed-dose combinations bring huge improvement in the adherence to and persistence in the treatment of hypertension. The combination therapy with fixed doses typically shows its effect with a small number of tablets or even by taking one tablet once a day, which improves  patients’ psychological condition to a great degree.

    Third, financial costs are an obstacle in controlling patients’ blood pressure. It turns out that combination therapy with fixed doses can be cheaper than the drugs administered separately. Combination therapy can reduce costs by prescribing less medication and can be offered among the most financially troubled patients.

    There are several medicine classes that can be used in combating hypertension: thiazide diuretics, calcium channel blockers, beta-blockers, alpha-blockers, ACE inhibitors, ARBs, and some centrally acting drugs.

    One of the most widely used combinations is a thiazide diuretic plus an ACE inhibitor/ARB. Since the use of fixed-dose combination for the treatment of hypertension is a new trend and method in clinical practice, more and more combination products are designed specifically, including thiazide diuretics and ACE-inhibitors/ARBs. In elderly patients treated with ACE inhibitors only, blood pressure target levels cannot be achieved. FDC with thiazide diuretics and ACE inhibitors often lead to beneficial effects, which proves that thiazide diuretics and ACE inhibitors are the ideal group. Diuretics cause an increased loss of sodium and intravascular volume depletion, which can lead to RAAS activation and this way – to enhance the antihypertensive effect of the ACE inhibitors.

    Based almost on the same mechanism, the combination of thiazide diuretic and ARB showed an additive antihypertensive effect. It is activated with the selective inhibition of ARB angiotensin ΙΙ, where the antihypertensive effect of thiazide diuretics is improved significantly. ARBs may also reduce potassium loss and hyperuricemia caused by thiazide diuretics due to the blocked secretion of aldosterone.

    Fixed-dose combinations of ARBs and thiazide diuretics demonstrate not only better performance, but also maintain a very good clinical practice tolerability profile.

    Tchaikapharma High Quality Medicines AD offers combinations containing a thiazide diuretic plus an ACE inhibitor/ARB with the following trade names and quantitative composition on the Bulgarian market:


    CG 029 – Co-Paxenе – 2/0.625 mg х 30 tabl.

    CG 030 – Co-Paxenе – 4/1.25 mg x 30 tabl.

    Irbesartan/ Hydrochlorothiazide:

    CF 945 – Co-Irbesso 150/12.5 mg – 30 mg x 30 tabl.
    CF 946 – Co-Irbesso 300/12.5 mg – 30 mg x 30 tabl.