In the second half of the double-blind phase, patients who had not achieved BP control had their treatment uptitrated and showed further significant increases in BP reduction by the end of this second 8-week treatment phase

In the second half of the double-blind phase, patients who had not achieved BP control had their treatment uptitrated and showed further significant increases in BP reduction by the end of this second 8-week treatment phase. eight weeks of treatment with olmesartan/amlodipine, compared with equivalent doses of olmesartan or amolodipine monotherapy ( 0.001), in the factorial Combination of Olmesartan Medoxomil and Amlodipine Besylate in Controlling High Blood Pressure (COACH) trial. About 85% of the maximal BP reductions after the 8-week treatment period were already observed after two weeks. Uptitration as necessary, with or without hydrochlorothiazide, allowed the majority of patients to achieve BP control in a 44-week open-label extension treatment period to the COACH trial. The use of olmesartan/amlodipine allowed up to 54% of patients, with previously inadequate responses to amlodipine or olmesartan monotherapy, to achieve their BP goals. Data from post-registration studies using tight BP control and forced titration regimens have further demonstrated the high efficacy of olmesartan/amlodipine in achieving BP goal rates. Moreover, consistent reductions in BP were observed over the 24-hour dosing interval using ambulatory measurements. Olmesartan/amlodipine was generally well tolerated over the short- and long-term, with a lower frequency of peripheral edema with olmesartan/amlodipine 40/10 mg than with amlodipine 10 mg monotherapy. 0.001) reduced by approximately 20% in the benazepril/amlodipine arm compared with the benazepril/HCTZ arm. However, these results should not be extrapolated to the general hypertensive population in regard to assuming that a RAS blocker/CCB combination is per se superior to a RAS blocker/thiazide diuretic combination since the patient population in ACCOMPLISH was not typical of the general hypertensive population: there was a high level of obesity and approximately 60% of patients were diabetic. Nonetheless, the combination of a RAS blocker plus a CCB was undoubtedly an effective combination in these patients, and supports the use of combination therapy comprising a RAS blocker and CCB to control BP and reduce CV risk in patients with hypertension, especially those with features of the metabolic syndrome such as obesity and diabetes. Another randomized trial, ONTARGET (Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial), demonstrated that the ARB telmisartan was equally as effective as the ACEI ramipril in reducing the incidence of CV events in high-risk patients.34 Importantly, there was a lower incidence of cough and angio-edema in patients who received telmisartan compared with those who received ramipril. This result is consistent with a large-scale observational study of more than 195,000 patients in the US Veterans Affairs Health Care System who initiated ACE therapy. The study found an increase in the incidence of angioedema associated with the use of ACEIs (1.97 cases/1000 person years) compared with other antihypertensive medications (0.51 cases/1000 person years), and that the risk of angioedema remained elevated with longer-term use, even beyond one year. 35 Taken together these findings support the rationale for combining an ARB and a CCB as an antihypertensive strategy. This notion is reflected by the recent European hypertension treatment guidelines in which combination therapy with an ARB or ACEI plus a CCB is indeed a recommended strategy.9,36 Olmesartan/amlodipine combination therapy Since ARBs inhibit the activity CBL2 of the RAS by blocking the angiotensin II type 1 (AT1) receptor, the efficacy of the ARBs depend upon their ability to inhibit AT1 receptor activation by angiotensin II. Pharmacodynamic studies have shown that ARBs, when given in their Gentamycin sulfate (Gentacycol) recommended doses, differ in their ability to block the AT1 receptor. These differences in AT1 receptor blockade may translate into differences between ARBs in their ability to control BP over 24 hours. This is in line with an independent meta-analysis of studies which used ambulatory BP monitoring (ABPM) to measure 24-hour BP control with ARBs. This meta-analysis found that the size of reduction in ambulatory SBP depended upon the drug used, and that the dose used affected the duration of the antihypertensive activity for both systolic and diastolic BP.37 Gentamycin sulfate (Gentacycol) In this regard, the ARB olmesartan medoxomil (hereafter referred to as olmesartan) is of interest since it has been shown in pharmacodynamic studies to produce a strong level of AT1 receptor blockade in relation to dose.38C40 Furthermore, direct comparison with several other ARBs has shown that olmesartan produces robust antihypertensive efficacy over 24 hours, the daytime, night-time, and end-of-dosing interval periods relative to losartan, candesartan or valsartan monotherapy, and Gentamycin sulfate (Gentacycol) was at least as efficacious as irbesartan.41C43 Clinical data suggest that olmesartan may protect against end-organ damage and, in this regard, renoprotective and anti-atherosclerotic.

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