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Hypertension is a serious public health concern with inadequate control of blood pressure (BP) worldwide. Contributing factors include low efficacy of drugs, underuse of combination therapies, irrational combinations, physicians' therapeutic inertia and poor adherence to treatment. Current guidelines recommend the use of initial (dual) combination therapy in high-risk patients for immediate BP response, better short- and long-term BP control, and continued/improved patient adherence. This article aims to review the existing evidence of triple-combination therapies with respect to efficacy, safety and adherence to treatment. It is estimated that three drugs are required to achieve BP control in approximately one-fourth to one-third of patients. Randomised controlled trials (RCTs) have shown that triple combinations of amlodipine/valsartan/hydrochlorothiazide, amlodipine/olmesartan/hydrochlorothiazide and amlodipine/telmisartan/hydrochlorothiazide produce greater BP reductions, with greater proportions of patients achieving BP control compared with dual therapies. Further evidence also demonstrates that triple-combination therapy is efficacious for moderate to severe hypertension, with substantial additional BP reduction over dual regimens. Both RCTs and post-marketing observational studies have shown consistent and comparable efficacy in both the general population and high-risk hypertensive subgroups. Triple therapies are generally well tolerated with adverse event profiles similar to dual regimens. In addition, fixed-dose combinations used as single pill improve patient adherence leading to better long-term BP control. Depending on regional circumstances, they may also be cost effective. Thus, single-pill triple combinations of different classes of drugs with complementary mechanisms of action help to treat patients to goal with improved efficacy and better adherence to treatment.

Aims: To compare the effects of losartan and amlodipine on myocardial structure and function in hypertensive patients with Type 2 diabetes and left ventricular hypertrophy., Methods: After a 4-week placebo period, patients were randomized to losartan 50 mg (n = 90) or amlodipine 5 mg (n = 91) for 12 months, with a doubling of the dose in patients who did not respond after 4 weeks. Blood pressure was measured in the clinic every month, while conventional echocardiography and acoustic densitometry (integrated backscatter analysis) were performed at the end of the placebo period and after 12 months of treatment., Results: Both drugs reduced systolic/diastolic blood pressure to a comparable extent. Losartan significantly reduced left ventricular mass index (-19%, P < 0.001), interventricular septal thickness (-16.6%, P < 0.01) and left ventricular posterior wall thickness in diastole (-13.7%, P < 0.01). Amlodipine also decreased such measurements (-10%, P < 0.01 for left ventricular mass index, -9.3%, P < 0.05 for interventricular septal thickness in diastole and -10.1%, P < 0.05 for posterior wall thickness in diastole), but to a lesser extent than losartan. Both drugs significantly increased the ratio of peak filling velocity at early diastole to that at atrial contraction (E/A ratio) and decreased isovolumetric relaxation time: +13.7% and -8.5% with losartan,(both P < 0.01), and +7.9% and -4.9%, with amlopidine (both P < 0.05). Losartan, but not amlodipine, significantly reduced the relative integrated backscatter compared to baseline of the intraventricular septum (-10%, P < 0.01), and of the left ventricular posterior wall (-12%, P < 0.01), while increasing the cyclic variation of integrated backscatter of both the intraventricular septum (+35%, P < 0.001) and the left ventricular posterior wall (+32%, P < 0.001)., Conclusions: Losartan provided a greater attenuation of left ventricular hypertrophy than amlodipine, seemingly as a result of a greater reduction of myocardial fibrosis., (© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.)

Hypertension is one of the major risk factors associated with cardiovascular diseases. A range of blood pressure-lowering agents is available including diuretics, alpha- and beta-blockers, aldosterone antagonists, calcium-channel blockers (CCB), angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB) and direct renin inhibitors (DRI). Most patients require two or more medications to control their blood pressures within normal ranges. When high blood pressure cannot be controlled by low-dose monotherapy, physicians employ either high-dose monotherapy or combination therapy. High-dose ARB monotherapy is more effective for reducing proteinuria against low-dose ARB monotherapy or CCBs. Combination therapy is recommended for hypertension patients to facilitate prompt maintenance of blood pressure. Single-pill combination therapy simplifies treatment and optimizes long-term compliance. Thiazide diuretics such as hydrochlorothiazide (HCTZ), alone or in combination are still widely used as first-line hypertension treatment. Recent studies have shown that double (CCB+ARBs) or triple (CCB+ARBs+HCTZ) combination therapies have a greater lowering efficacy and are better tolerated. Moreover, the use of DRIs has been patented and proven effective in selected categories of hypertensive patients with or without concomitant target organ damage (TOD).

The aim of this study was to compare the effects of telmisartan/hydrochlorothiazide (HCTZ) vs lisinopril/HCTZ combination on ambulatory blood pressure and cognitive function in elderly hypertensive patients. A total of 160 patients, 76 men and 84 women, aged 61-75 years, with sitting diastolic blood pressure (DBP)>90 mmHg and <110 mmHg and systolic blood pressure (SBP)>140 mmHg were randomized to receive temisartan 80 mg/HCTZ 12.5 mg o.d. or lisinopril 20 mg/HCTZ 12.5 mg o.d. for 24 weeks, according to a prospective, open-label, blinded end point, parallel-group design. At the end of a 2-week wash-out period and after 12 and 24 weeks of active treatment, 24-h noninvasive ambulatory BP monitoring (ABPM) was performed and cognitive function was evaluated through six different tests (verbal fluency, Boston naming test, word-list memory, word-list recall, word-list recognition and Trails B). Both treatments significantly reduced ambulatory BP. However, the telmisartan/HCTZ combination produced a greater reduction in 24-h, day-time and night time ABPM values. Lisinopril/HCTZ did not induce significant changes in any of the cognitive function test scores at any time of the study, whereas at both 12 and 24 weeks telmisartan/HCTZ significantly improved the word-list memory score (+17.1 and +15.7%, respectively, P<0.05 vs baseline), the word-list recall score (+13.5 and +16.9%, P<0.05) and the Trails B score (-33 and -30.5%, P<0.05). These results suggest that in elderly hypertensive patients treatment with telmisartan/HCTZ produces a slightly greater reduction in ambulatory BP than lisinopril/HCTZ combination and, unlike this latter, improves some of the components of cognitive function, particularly episodic memory and visuospatial abilities.

Abstract Background Inadequate blood pressure control and poor adherence to treatment remain among the major limitations in the management of hypertensive patients, particularly of those at high risk of cardiovascular events. Preliminary evidence suggests that home blood pressure telemonitoring (HBPT) might help increasing the chance of achieving blood pressure targets and improve patient’s therapeutic adherence. However, all these potential advantages of HBPT have not yet been fully investigated. Methods/design The purpose of this open label, parallel group, randomized, controlled study is to assess whether, in patients with high cardiovascular risk (treated or untreated essential arterial hypertension - both in the office and in ambulatory conditions over 24 h - and metabolic syndrome), long-term (48 weeks) blood pressure control is more effective when based on HBPT and on the feedback to patients by their doctor between visits, or when based exclusively on blood pressure determination during quarterly office visits (conventional management (CM)). A total of 252 patients will be enrolled and randomized to usual care (n=84) or HBPT (n=168). The primary study endpoint will be the rate of subjects achieving normal daytime ambulatory blood pressure targets ( Discussion The TELEBPMET Study will show whether HBPT is effective in improving blood pressure control and related medical and economic outcomes in hypertensive patients with metabolic syndrome. It will also provide a comprehensive understanding of the psychological determinants of medication adherence and blood pressure control of these patients. Trial registration Clinical Trials.gov: NCT01541566