Patient’s adherence on pharmacological therapy for benign prostatic hyperplasia (BPH)-associated lower urinary tract symptoms (LUTS) is different: is combination therapy better than monotherapy?

BPH represents a major public health issue because of its increasing prevalence, progressive nature and treatment costs [19‐21]. Current guidelines recommend the use of ABs and 5ARIs as monotherapy or in combination for the treatment of BPH-associated LUTS [5,6]. However, a gap exists between guidelines and actual clinical practice [10,12, 21]. In “real life” the low adherence to prescribed medications is a recognized problem for chronic diseases [13]. Some studies deeply evaluated the problems of drug prescription and adherence for BPH as well as its impact on the clinical outcomes [12, 19, 21‐23]. All showed concordant results: 1) the reported adherence in clinical trials is higher than that observed in real life; 2) the duration of treatment for BPH-associated LUTS is extremely short; 3) the adherence to treatment is generally low and 4) this might negatively influence BPH-related hospitalization rates.

By and large, patient adherence, or compliance, to a prescribed drug treatment is defined as the extent to which a person's attitude in terms of taking medication coincides with the medical or health advice he receives.

Adherence or compliance to a drug regimen is divided to primary non-compliance, for example when one receives a prescription, but does not have it made up at a pharmacy. Forms of secondary non-compliance include taking incorrect doses of the prescribed medication, taking the medication at wrong times, forgetting one or more doses of the medication, or altogether stopping the medication, either by ceasing to take the medication sooner than the doctor recommended or failing to obtain a repeat prescription [24]. Poor adherence to a therapeutic regimen has been identified as a major public health problem that may have a major impact on clinical outcomes [25].

The lack of a valid method for measuring compliance is by itself a major barrier to compliance research. Both direct and indirect measures have been sought in order to quantify compliance, and although direct measures are considered to be the most accurate, their invasive nature makes them unacceptable and inappropriate to use. Indirect measurements are therefore more frequently reported in the literature and include measures such as interviews, diaries, tablet counts, and prescription refill dates. Interviews and all self-report methods are vulnerable to overestimates of compliance and underestimates of non-compliance [26]. There are inherent limitations with these methods for generating valid and reliable data to give an accurate estimate of extent of patient adherence. Data from administrative databases, used in our and in other studies, are another indirect but reliable method of estimating drug consumption and patient adherence to a certain regimen [12, 21, 22]. Patient adherence to medical treatment is generally suboptimal irrespective of the drug or the treated condition. Studies on patient adherence on pharmacological therapy for the treatment of hypertension have shown that 50 % of patients discontinue their medication while two-thirds of patients that stay on treatment seem to lower their drug doses [26].

Although data regarding pharmacotherapy for BPH-associated LUTS are limited, a recent study from France confirmed that the 1-year adherence ranges between 21 % to 26 [21]. Madershbacher in 2007, looking at the results from clinical trials, depicted a clinical scenario describing the adherence rates of different therapeutic regimens. They found that the discontinuation rates in the 5-ARIs trials were lower than in the AB trials; and confirmed a 2-year discontinuation rate of 10–20 % of patients under 5ARIs. On the other hand, discontinuation rates were lower for combination therapy (18 %) compared to finasteride (24 %) and doxazosin (27 %) monotherapy [19]. Even more interesting, these data are in contradiction with our results: a statistically significant lower adherence for CT compared to either AB or 5ARI monotherapies. These discrepancies are probably due to different study design. Our “real life” approach shows that patients abandon CT for several reasons that should be better investigated. Moreover, we found that the prolonged use of 5ARIs and adherence to the prescribed regimen were significantly associated with a lower risk of BPH-related hospitalization and surgery.

In the BPH population the decision to adhere to pharmacological treatment is primarily based on the patient’s perception of bother due to LUTS and its impact on quality of life, and definitely depends on patient expectations and beliefs. The patient’s perspective towards BPH and its management play a major role in the decision to initiate, continue or abandon treatment [27]. Even if we recognize that the reasons for the lack of drug adherence are multiple and difficult to analyze (especially using this methodological approach), it is important to remember that the strategy “enhance compliance by decreasing the number of pills” has been widely demonstrated in other fields of medicine [14]. There is convincing evidence from the literature suggesting that adherence is inversely associated with the complexity of the drug regimen. In this concept, the so-called fixed-dose combination (FDC) drugs (2 or more drugs produced in a single pill/tablet) have been developed in order to treat one disease with complementary actions (e.g., diabetes mellitus, asthma) or treat multiple clinical conditions (e.g., hypertension and hyperlipidemia) [14]. A FDC regime containing 0.5 mg of dutasteride and 0.4 mg of tamsulosin in the same pill is available for the treatment of BPH-associated LUTS.

Recent reports show that the use of FDC is associated with lifestyle advice resulted in rapid and sustained improvements in men with moderate BPH-associated LUTS [28] and that FDC is a cost-effective option in a estimated lifetime budget cost model [29] .

Even though the parameters that would modify patient’s adherence are multiple and complex (spanning from awareness campaigns to better patient counselling) it seems reasonable to support the use of FDC for BPH-associated LUTS in order to decrease patient withdrawal and to increase adherence to the guidelines.

Several limitations of our study should be acknowledged. Studies based on data from administrative databases cannot be considered efficacy studies and do not include clinical variables or patient reported outcomes [30]. Another serious limitation is the imbalance between regimens, but this reflects the prescription attitudes. Moreover the current analysis is specific to the Italian situation and its generalization should be done with caution.

In this study we demonstrated that in “real life” patient adherence to BPH medication is different to that reported in clinical trials and that patients under CT abandon treatment more frequently that patients under monotherapy do.