Fixed combination of irbesartan and hydrochlorothiazide in the management of hypertension

Approximately 25% of the adult population worldwide is hypertensive and thus at risk of cardiovascular morbidity and mortality. Despite the availability of many antihypertensive drugs, at least 50% of patients do not achieve blood pressure (BP) targets and thus remain at increased cardiovascular risk. Fixed-dose (FD) irbesartan/hydrochlorothiazide (HCTZ) is an antihypertensive combination therapy approved for the treatment of patients whose BP is not adequately controlled on monotherapy and for initial treatment of patients likely to need multiple drugs to achieve their BP goal. The efficacy and tolerability of FD irbesartan/HCTZ has been demonstrated in both patient populations in large multicenter studies. In patients failing antihypertensive monotherapy, FD irbesartan/HCTZ (150/12.5 mg) has been shown to be more effective than FD valsartan/HCTZ (80/12.5 mg) and at least comparable to FD losartan/HCTZ (50/12.5 mg). In patients with moderate or severe hypertension receiving FD irbesartan/HCTZ as initial therapy, this combination achieved more rapid BP reductions compared with irbesartan monotherapy and enabled a greater proportion of patients with severe hypertension to achieve their BP target. FD irbesartan/HCTZ is thus a valuable addition to the clinician’s armamentarium for the management of hypertension and should help more patients achieve their BP target

Treatment of peripheral arterial disease using stem and progenitor cell therapy

Peripheral arterial disease (PAD) is a highly prevalent atherosclerotic syndrome associated with significant morbidity and mortality. PAD is most commonly caused by atherosclerosis obliterans (ASO) and thromboangiitis obliterans (TAO), and can lead to claudication and critical limb ischemia (CLI), often resulting in a need for major amputation and subsequent death. Standard treatment for such severe cases of PAD is surgical or endovascular revascularization. However, up to 30% of patients are not candidates for such interventions, due to high operative risk or unfavorable vascular involvement. Therefore, new strategies are needed to offer these patients a viable therapeutic option. Bone-marrow derived stem and progenitor cells have been identified as a potential new therapeutic option to induce angiogenesis. These findings prompted clinical researchers to explore the feasibility of cell therapies in patients with peripheral and coronary artery disease in several small trials. Clinical benefits were reported from these trials including improvement of ankle-brachial index (ABI), transcutaneous partial pressure of oxygen (TcO2), reduction of pain, and decreased need for amputation. Nonetheless, large randomized, placebo-controlled, double-blind studies are necessary and currently ongoing to provide stronger safety and efficacy data on cell therapy. Current literature is supportive of intramuscular bone marrow cell administration as a relatively safe, feasible, and possibly effective therapy for patients with PAD who are not subjects for conventional revascularization.Clinical RelevanceThis article describes the background and first results of stem and progenitor cell therapy in patients with critical limb ischemia not suitable for revascularization. The principle as far as it is understood and the methods are described. Compelling evidence suggests that progenitor cell therapy might become a useful adjunct to the treatment options at present. Due to poor prognosis and the increasing number of patients, there is a need for new therapeutic methods. The article gives an overview of first encouraging results provided by early-phase clinical trials. Challenges in this new therapeutic option still include open questions such as cell phenotype, processing, dosing, route of optimal delivery, and frequency of application. Validation by more rigorous controlled trials involving homogenous patient populations are required to confirm the first hopeful results

Office and ambulatory blood pressure control with a fixed-dose combination of candesartan and hydrochlorothiazide in previously uncontrolled hypertensive patients: results of CHILI CU Soon

Thomas Mengden1, Reinhold Hübner2, Peter Bramlage31Kerckhoff-Klinik GmbH, Bad Nauheim, 2Takeda Pharma GmbH, Aachen, 3Institut für Kardiovaskuläre Pharmakologie und Epidemiologie, Mahlow, GermanyBackground: Fixed-dose combinations of candesartan 32 mg and hydrochlorothiazide (HCTZ) have been shown to be effective in clinical trials. Upon market entry we conducted a noninterventional study to document the safety and effectiveness of this fixed-dose combination in an unselected population in primary care and to compare blood pressure (BP) values obtained during office measurement (OBPM) with ambulatory blood pressure measurement (ABPM).Methods: CHILI CU Soon was a prospective, noninterventional, noncontrolled, open-label, multicenter study with a follow-up of at least 10 weeks. High-risk patients aged ≥18 years with previously uncontrolled hypertension were started on candesartan 32 mg in a fixed-dose combination with either 12.5 mg or 25 mg HCTZ. OBPM and ABPM reduction and adverse events were documented.Results: A total of 4131 patients (52.8% male) with a mean age of 63.0 ± 11.0 years were included. BP was 162.1 ± 14.8/94.7 ± 9.2 mmHg during office visits at baseline. After 10 weeks of candesartan 32 mg/12.5 mg or 25 mg HCTZ, mean BP had lowered to 131.7 ± 10.5/80.0 ± 6.6 mmHg (P < 0.0001 for both comparisons). BP reduction was comparable irrespective of prior or concomitant medication. In patients for whom physicians regarded an ABPM to be necessary (because of suspected noncontrol over 24 hours), ABP at baseline was 158.2/93.7 mmHg during the day and 141.8/85.2 mmHg during the night. At the last visit, BP had significantly reduced to 133.6/80.0 mmHg and 121.0/72.3 mmHg, respectively, resulting in 20.8% being normotensive over 24 hours (<130/80 mmHg). The correlation between OBPM and ABPM was good (r = 0.589 for systolic BP and r = 0.389 for diastolic BP during the day). Of those who were normotensive upon OBPM, 35.1% had high ABPM during the day, 49.3% were nondippers, and 3.4% were inverted dippers. Forty-nine adverse events (1.19%) were reported, of which seven (0.17%) were regarded as serious.Conclusion: Candesartan 32 mg in a fixed-dose combination with either 12.5 mg or 25 mg HCTZ is safe and effective for further BP lowering irrespective of prior antihypertensive drug class not being able to control BP.Keywords: ambulatory blood pressure, office blood pressure, normalization, respons

Management of hypertension with fixed dose combinations of candesartan cilexetil and hydrochlorothiazide: patient perspectives and clinical utility

Hypertension treatment and control is largely unsatisfactory when guideline-defined blood pressure goal achievement and maintenance are considered. Patient- and physician-related factors leading to non-adherence interfere in this respect with the efficacy, tolerability, and convenient use of pharmacological treatment options. Blockers of the renin–angiotensin system (RAS) are an important component of antihypertensive combination therapy. Thiazide-type diuretics are usually added to increase the blood pressure lowering efficacy. Fixed drug–drug combinations of both principles like candesartan/hydrochlorothiazide (HCTZ) are highly effective in lowering blood pressure while providing improved compliance, a good tolerability, and largely neutral metabolic profile. Comparative studies with losartan/HCTZ have consistently shown a higher clinical efficacy with the candesartan/HCTZ combination. Data on the reduction of cardiovascular endpoints with fixed dose combinations of antihypertensive drugs are however scarce, as are the data for candesartan/HCTZ. But many trials have tested candesartan versus a non-RAS blocking comparator based on a standard therapy including thiazide diuretics. The indications tested were heart failure and stroke and particular emphasis was put on elderly patients or those with diabetes. In patients with heart failure, for example, the fixed dose combination might be applied in patients in whom individual titration resulted in a dose of 32 mg candesartan and 25 mg HCTZ which can then be combined into one tablet to increase compliance with treatment. Also in patients with stroke the fixed dose combination might be used in patients in whom maintenance therapy with both components is considered. Taken together candesartan/HCTZ assist both physicians and patients in achieving long-term blood pressure goal achievement and maintenance

Significance of initial blood pressure and comorbidity for the efficacy of a fixed combination of an angiotensin receptor blocker and hydrochlorothiazide in clinical practice

Roland E Schmieder1, Markus Schwertfeger2, Peter Bramlage31Department of Nephrology and Hypertension, University Hospital of Erlangen; Germany; 2Sanofi-Aventis Deutschland GmbH, Berlin, Germany; 3Institute of Cardiovascular Pharmacology and Epidemiology, Mahlow, GermanyBackground: Two-thirds of all patients with arterial hypertension need drug combinations to achieve blood pressure (BP) goals. Fixed combinations have high efficacy and result in high patient compliance. 300 mg irbesartan plus 25 mg hydrochlorothiazide (HCTZ) has been investigated only in clinical trials but not in daily practice.Methods: A multicenter, noninterventional, noncontrolled observational study with 8123 patients seen by 1604 physicians in daily practice. BP reduction (office measurements), co-morbid disease and tolerability were documented over a 6-month observational period.Results: At mean baseline BP of 161 ± 15/94 ± 10 mmHg, administering of fixed combination resulted in a substantial BP reduction averaging 28 ± 15/14 ± 10 mmHg (P < 0.001). Decrease of systolic BP ran parallel with increasing systolic baseline BP (Spearman’s Rho –0.731; P < 0.0001; diastolic BP vs diastolic baseline BP Rho 0.740; P < 0.0001), independent from patient characteristics (age, obesity, diabetes or nephropathy) but enhanced with short history of hypertension (P < 0.0001 vs long history), prior beta blockers (P = 0.001 vs prior angiotensin receptor blockers [ARBs]), prior calcium channel blockers (P = 0.046 vs prior ARBs) and no prior medication (P = 0.012 vs prior ARBs). High compliance (>98%) and low incidence of adverse events (0.66%) were documented.Conclusions: The fixed combination of 300 mg irbesartan with 25 mg HCTZ was efficacious and tolerable in an unselected patient population in primary care.Keywords: hypertension, combination therapy, obesity, irbesartan, noninterventional study, diuretic