More focus on therapeutic targets and improved tolerability in hypertension.

Thomas Hedner, Sverre E Kjeldsen, Krzysztof Narkiewicz, Susanne Oparil
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Abstract

During recent years, there have been increased efforts in most countries to improve management of hypertensive patients in order to reduce cardiovascular morbidity and mortality in the population. According to current recommendations of management of hypertension, about three-quarters of those over the age of 65 years, more than half of those aged over 55 years, and about one-third of adults over 16 years of age are considered hypertensive (1–3). When non-pharmacological efforts are insufficient, a large proportion of the adult population will therefore, according to current guidelines, require pharmacological intervention to lower blood pressure (1–3). Numerous studies performed in many countries around the world have repetitively shown that adequate blood pressure control is achieved and maintained only in a limited proportion of the hypertensive population (1,2). Compared with those with lower blood pressure levels, treated patients with a blood pressure of 140 and/or 90 mmHg or more will be at excess cardiovascular risk and more likely to suffer negative health consequences. Poor control of hypertension therefore remains an important issue and deserves considerably more focus as well as increased efforts from the medical community. One important reason for poor hypertension control seems to be that many physicians often base antihypertensive treatment on monotherapy, although there may be a clear need for add-on therapy (4). In the current issue of Blood Pressure, the topic of combination therapy is addressed in a series of communications. Weycker et al. (5) present data from a large database survey showing the effectiveness of add-on treatment with amlodipine to obtain an improved systolic and diastolic blood pressure reduction in patients on valsartan monotherapy. Trenkwalder et al. (6), also studying amlodipine and valsartan, find that the combination lowers blood pressure in patients not controlled by an angiotensin-converting enzyme inhibitor/calcium-channel blocker combination. Nickenig and coworkers (7) find that the fixed combination of aliskiren/hydrochlorothiazide (HCTZ) more effectively lowers blood pressure in aliskiren non-responders with a similar tolerability. Börner et al. (8) describe the effectiveness of a candesartan/HCTZ combination providing an improved blood pressure reduction compared with candesartan monotherapy with maintained tolerability. Taken together, in patients with insufficient hypertension control on monotherapy with an angiotensin 1 receptor antagonist or a renin inhibitor, combination with a calcium antagonist or HCTZ will provide an improved control and a maintained tolerability. These data are in agreement with data from a previous meta-analysis (9) of a large series of randomized, double-blind, placebo-controlled antihypertensive combination trials, demonstrating that combination therapy improves antihypertensive efficacy as well as tolerability. Combination therapy produces an additive effect of the blood pressure lowering responses from the individual components of the first and second drugs. Importantly, in some trials, major blood pressure reductions by combination therapy have been achieved when the individual antihypertensive agents were administered at half-standard doses. Although seemingly simple to implement in most hypertension clinics, achieving target pressures in the hypertensive population remains a difficult issue. Importantly, adherence to the prescribed treatment regimen is a key determinant of the success of blood pressure control in most patient populations (10). Several known factors influence compliance with the antihypertensive lifestyle changes and drug therapy. Such factors include a high acquisition cost of drugs, complexity of the treatment regimen, patient information related to the hypertensive disease complications and the benefit of treatment. Also of importance are the availability of the physician and the ease of obtaining prescription medication. In addition to that, a Blood Pressure. 2008; 17 (Suppl 2): 3–4
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Post-registration studies for the evaluation of antihypertensive drugs. Effect of fixed dose combinations of metoprolol and amlodipine in essential hypertension: MARS--a randomized controlled trial. Efficacy and safety of valsartan in hypertensive Taiwanese patients: post-marketing surveillance study. Efficacy and safety of early versus late titration of fixed-dose irbesartan/hydrochlorothiazide: ACTUAL study. Clevidipine for severe hypertension in patients with renal dysfunction: a VELOCITY trial analysis.
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