Achieving better blood pressure control

Primary hypertension is a polygenic condition with variable contribution from environmental factors. Not surprisingly, there are differential responses to both non‐pharmacological and pharmacological antihypertensive treatments within the population of hypertensive patients. In order to achieve maximal risk reduction, blood pressure (BP) should be reduced to below 140/90 mmHg in lower risk hypertensive patients, and even lower (<130/80 mmHg) if additional risk factors such as diabetes or renal disease are present [1]. Despite the availability of multiple classes of antihypertensive agents that lower BP by different mechanisms, the treatment of hypertension remains a difficult task. In terms of BP lowering effects, it is usually not possible to predict which type of agent is the most appropriate for a given patient. Consequently, in most hypertensive patients, target BPs are usually not reached by the use of monotherapies [2,3]. However, a strategy of combining medications acting by different mechanisms makes it possible to achieve considerable gains in terms of antihypertensive efficacy. This is due to the synergistic effects on the cardiovascular system of antihypertensive medications that have distinct mechanisms of action [4].

When combining two or several antihypertensive medications from different classes, it is important to select combinations of drugs that have complementary effects on BP lowering as well as reduction of adverse events [1]. In recent years, use of fixed‐low‐dose combinations of antihypertensive medications as first‐line treatment has increased greatly, since studies have shown that this approach is likely to both increase the chance of controlling the patient's BP and limit the occurrence of dose‐related adverse effects [5,6].

In the present issue of Blood Pressure, Ruilope and co‐workers [7] argue for wider use of fixed‐dose antihypertensive combinations based on both individual patient benefits and, importantly, also on greater public health and societal value. This Drug Therapeutic Supplement also deals with the issue of which drugs to combine. As demonstrated by Tuomilehto et al. [8] and Schumacher and Mancia [9], a fixed‐dose angiotensin II receptor blocker (ARB)‐diuretic combination has greater or comparable antihypertensive efficacy than ARB treatment alone without reduced tolerability. Most combination regimens currently available for clinical use include an inhibitor of the renin–angiotensin system (RAS) and a diuretic, but a fixed‐dosed combination regimen that includes a calcium‐channel blocker and an angiotensin‐converting enzyme (ACE) inhibitor is also widely used and has recently been shown to have outcome advantages over a combination of the same ACE inhibitor and a diuretic in the ACCOMPLISH trial [10]. Ueng et al [11] demonstrate that the dihydropyridine calcium‐channel blocker amlodipine and the ACE inhibitor benazepril, when combined, have complementary effects on BP, with impressive efficacy in rapid attainment of BP targets as well as levels of BP achieved.

Importantly, as pointed out by Ruilope and coworkers [7], combinations of drugs from different antihypertensive classes may have both synergistic or additive antihypertensive properties and the ability to diminish each others' untoward hemodynamic or metabolic effects. Importantly, beneficial fixed‐dose combinations containing optimal doses can be selected as initial therapy, thereby facilitating rapid BP control and minimizing adverse effects in the newly diagnosed hypertensive [6].

Poor control of hypertension remains an issue in most parts of the world. Failure to attain BP goals is related to multiple factors, e.g. insufficient efficacy of available single antihypertensive agents, poor adherence to prescribed medication, and reluctance of many physicians to treat aggressively, including combining antihypertensive medications to reach target BPs [5]. Most guidelines for the management of high BP advocate a strategy of early combination therapy with low doses of two antihypertensive drugs for management of mild/moderate arterial hypertension. Recent evidence suggests that this strategy may be preferred over monotherapy [5]. The superior effectiveness of low‐dose fixed‐dose combination therapy relates to both better antihypertensive efficacy and higher BP response rates, in part due to improved medication adherence, and to greater tolerability due to reduced rates of adverse effects [12]. In addition, fixed‐dose combination therapy often costs less than free combinations of the component drugs. Because of all of these benefits, increased use of low dose fixed combination therapies will likely translate into a further reduction of hypertension‐related cardiovascular/cerebrovascular morbidity and mortality in the population [13].