Multiple weekend sessions
Getting Patients to BP Goals:
More Combo Therapy

R.E. Schmieder, Germany

Despite the well established link between hypertension and mortality, more than two-thirds of Europeans with high blood pressure (BP) receive no antihypertensive therapy and no more than 10% of patients reach goal BP values (<140 mm Hg SBP and <90 mm Hg DBP). Several weekend symposia looked at how to improve patient care by better managing patient therapy.

In reviewing the unmet needs of hypertension, Prof. Roland E. Schmieder, Friedrich-Alexander Universitat, Erlangen (Germany), said the poor control of BP is partly attributable to the lack of therapeutic escalation, since less than one-third of patients receive any increase in medication. In a satellite symposium on sunday, Dr. Schmieder noted that current guidelines recommend combination therapy in two settings: for patients who fail to achieve BP goals on single agents and as initial therapy in patients at higher cardiovascular risk.

H. Schunkert, Germany

In another symposium, co-chair Dr. Heribert Schunkert, Lübeck (Germany), noted (like many other symposium presenters across the weekend) that guidelines agree that most patients will require combination therapy. In addition, he said, low dose combination is superior to doubling the dose of an individual agent from both the efficacy and tolerability perspectives. The question of which combination to choose is a difficult one. As inconsistent as guidelines are with regard to optimal first-line agents, they are even less consistent regarding optimal combinations of therapies. In another session, Prof. Neil R.

N.R. Poulter, UK

Dr. Poulter was one of four executive committee members overseeing the large ASCOT primary prevention study. After a median follow-up of 5.4 years, the trial of more than 19,000 patients was halted due to superior efficacy of amlodipine/perindopril compared to an atenolol/thiazide combination. For the primary endpoint of non-fatal MI and fatal CHD, there was a non-significant reduction of about 10%, but there were highly significant differences seen for other endpoints (Figure 1). Benefits were apparent and significant for total cardiovascular events and procedures in all 18 pre-specified subgroups (Figure 2).

Figure 1

Figure 2

In his saturday symposium session, Dr. Schunkert noted recent studies of an ARB/hydrochlorothiazide (HCTZ) combination suggest particular efficacy in lowering blood pressure in difficult to treat patients, including those with severe hypertension, left ventricular hypertrophy, isolated systolic hypertension, and obesity. The long term beneficial effects of this therapeutic strategy have been documented in the LIFE trial.

Fixed-Dose Combinations

M. Burnier, Switzerland

Fixed-dose combinations have advantages over separate-dose combinations since nonadherence is a major factor in the clinical effectiveness of prescribed antihypertensive therapy. In a satellite symposium, Prof. Michel Burnier of University Hospital, Lausanne (Switzerland), cited the ACCOMPLISH trial, the first to show that a fixed-dose combination of the ACE-inhibitor benazepril with the CCB amlodipine provided extra benefits in reducing hypertension-related mortality. In addition, this combination was particularly effective in controlling BP in high-risk patients.

Dr. Burnier reviewed two other trials. The INCLUSIVE study demonstrated that the ARB irbesartan/HCTZ combination was effective and well-tolerated in a diverse group of patients uncontrolled on monotherapy and in whom goal attainment was particularly challenging, including the elderly or those with diabetes or metabolic syndrome. And in the RAPiHD trial, initial treatment of patients with moderate or severe hypertension, irbesartan/HCTZ produced significantly greater and more rapid reduction in systolic BP compared with either component alone. Also, a greater proportion of patients with severe hypertension achieved their target BP level compared to irbesartan monotherapy. The combination was well-tolerated by patients of all ages and had a safety profile similar to monotherapy.

R. Kreutz, Germany

The U.S. Food and Drug Administration recently approved a fixed-dose combination of olmesartan and amlodipine for treating hypertension. (This combination has been filed with the European regulatory authorities.) Dr. Reinhold Kreutz, Charite – University Medicine, Berlin (Germany), speaking in satellite symposium, said the FDA approval was granted based on a U.S. study demonstrating that this combination was superior in terms of better BP lowering effects compared to either monotherapy (p < 0.001) after 8 weeks. Moreover, marked reductions in BP were seen even with low doses of combination therapy compared to higher doses of monotherapy. No increase in adverse events was observed with combination therapy, relative to monotherapy groups, indeed there was evidence that adding olmesartan to amlodipine 10 mg reduced the incidence of ankle oedema relative to amlodipine monotherapy.

A. de la Sierra, Spain

In the same symposium, Dr. Alejandro de la Sierra, Barcelona (Spain), added that the combination of olmesartan with amlodipine allows patients to benefit not only from increased BP-lowering efficacy, but also from the additional cardiovascular and renal effects associated with olmesartan and amlodipine. Important ancillary actions have been demonstrated, he said, in studies that assessed olmesartan-mediated reduction of endothelial inflammation as well as reversal of both vascular remodeling and carotid atherosclerosis. Evaluation of olmesartan in primary prevention of microalbuminuria is underway.

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