Many factors have been shown to contribute to adherence and these have been extensively reviewed (34 - 36).Two of the most important factors contributing to poor adherence are undoubtedly the asymptomatic and lifelong nature of the disease. Other potential determinants of adherence may be related to:

- demographic factors such as age and education;
- the patient's understanding and perception of hypertension (37);
- the health care provider's mode of delivering treatment;
- the relationships between patients and health care professionals;
- health systems influences; and
- complex antihypertensive drug regimens (38).

Poor socioeconomic status, illiteracy and unemployment are important risk factors for poor adherence (39,40). Other important patient-related factors may include understanding and acceptance of the disease, perception of the health risk related to the disease, awareness of the costs and benefits of treatment, active participation in monitoring (41) and decision-making in relation to management of the disease (42).

The influence of factors related to the health care provider on adherence to therapy for hypertension has not been systematically studied. Some of the more important factors probably include lack of knowledge, inadequate time, lack of incentives and feedback on performance. Multifaceted educational strategies to enhance knowledge, audit with feedback on performance, and financial incentives are some of the interventions that should be tested for their effectiveness (43 - 45).

The responsibility for adherence must be shared between the health care provider, the patient and the health care system. Good relationships between the patients and their health care providers are therefore imperative for good adherence. Empathetic and non-judgemental attitude and assistance, ready availability, good quality of communication and interaction are some of the important attributes of health care professionals that have been shown to be determinants of the adherence of patients (46).

Health systems-related issues also play an important role in the promotion of adherence. In most low-income countries supplies of medications are limited and they often have to be bought out-of-pocket. Strategies for improving access to drugs such as sustainable financing, affordable prices and reliable supply systems have an important influence on patient adherence, particularly in poorer segments of the population (47). Focusing on improving the efficiency of key health system functions such as delivery of care, financing and proper pharmaceutical management can make a substantial contribution to improving the adherence rates of patients with hypertension and patients with chronic illnesses in general.

Some of the better-recognized determinants of adherence to antihypertensive therapy are related to aspects of the drug treatment itself (46,48 - 55) and include drug tolerability, regimen complexity, drug costs and treatment duration.

Some investigators have speculated that poor adherence can be explained in part by properties of the medications such as tolerability. However, a discrepancy has been noted between data on adherence in relation to drug tolerability that are obtained from randomized controlled trials and those obtained from observational studies. For example pooled results from head-to-head randomized controlled trials that recorded discontinuation of medications due to adverse events have demonstrated that significantly fewer patients discontinued treatment with thiazide diuretics than discontinued treatment with beta-blockers and alpha-adrenergic blockers (46,48). However a recent review based on observational studies has reported that initial treatment with newer classes of drug such as angiotensin II antagonists, angiotensin converting enzyme inhibitors and calcium channel blockers favoured adherence to treatment (22).

It has been argued that information on adherence and the factors that contribute to it is better obtained from observational studies than from randomized clinical trials (49) because the stricter selection criteria and structured protocols used in randomized clinical trials may preclude generalization to patient behaviour in the real world. The role of drug tolerability in adherence to antihypertensive medication remains a topic for debate (50 - 53) and warrants further investigation.

The complexity of the regimen is another treatment-related factor that has been identified as a possible cause of poor adherence. Frequency of dosing, number of concurrent medications and changes in antihypertensive medications are some of the factors that contribute to the complexity of a regimen and these have been investigated in many observational studies (46). Fewer daily doses of antihypertensives (56,57), monotherapies and fewer changes in antihypertensive medications (less treatment turbulence) have all been associated with better adherence (54,55).