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Abstract Objective: To contemplate how initial antihypertensive therapy with fixed-dose combinations (FDC) might be incorporated into clinical practice, based on a compilation of evidence comparing FDCs with monotherapy and loose-dose combinations in varying patient populations. Methods: A non-systematic search of PubMed (from 2007 to 2012) was performed for randomized, controlled trials in order to capture the evidence on FDC versus monotherapy and loose-dose combinations as first-line therapy. The literature search focused on calcium channel blocker (CCB)-renin angiotensin system (RAS) blocker combinations. Additionally, any relevant papers known to the authors were included. International recommendations from published hypertension treatment guidelines were also consulted. Results: The results of this literature review identified two emergent issues. Firstly, there is a discord between antihypertensive use and actual blood pressure (BP) control achieved - despite an increase in the use of antihypertensives over the last 10 years, BP control rates remain low. Secondly, a greater association between BP and cardiovascular risk in Asians may magnify this discrepancy. A number of international guidelines are recommending early combination therapy, such as CCB-RAS blocker combinations in the majority of patients based on the available evidence, with such combinations showing benefits in terms of compliance, BP lowering and control, and safety. Additionally, recent studies have indicated that improved BP control may be achieved with simplified guidelines and the use of FDCs. Overall, these findings indicate that FDC could be used as first-line. Conclusions: The findings from this literature review suggest that physicians may need to readdress their approach to antihypertensive treatment. Earlier use of antihypertensive FDC (including first-line) may help to shrink the current gap between antihypertensive use and BP target control achieved. Most guidelines acknowledge that combination therapy is required in the majority of patients, and FDC are regarded as a suitable alternative, having demonstrated better compliance compared with loose-dose combinations. [ABSTRACT FROM AUTHOR]

A variety of therapeutic agents or chemical substances can induce either a transient or persistent increase in blood pressure or interfere with the blood pressure-lowering effects of antihypertensive drugs. Some agents either cause sodium retention and extracellular volume expansion or directly or indirectly activate the sympathetic nervous system. Other substances act directly on arteriolar smooth muscle or do not have a defined mechanism of action. Some medications that usually lower blood pressure may paradoxically increase blood pressure, and an increase in pressure may be encountered after their discontinuation. In general, these pressure increases are small and transient; however, severe hypertension involving encephalopathy, stroke, and irreversible renal failure have been reported. Careful evaluation of a patient's drug regimen may identify chemically induced hypertension and obviate unnecessary evaluation and direct to the optimal antihypertensive therapy. The present review summarizes the therapeutic agents or chemical substances that elevate blood pressure and their mechanisms of action. [ABSTRACT FROM AUTHOR]

It is well established that elevated blood pressure is a major risk factor for cardiovascular and cerebrovascular events, and that controlling hypertension reduces these risks. Although most classes of antihypertensive agents play a role in risk reduction, none offers blanket reductions for all adverse events. The beta-blockers, while the agents of choice for those with ischemic heart disease and for disease states requiring reducing heart rate, are inappropriate first-line therapies in patients whose primary concern is stroke risk reduction. In patients who require heart rate-lowering therapy but who cannot tolerate beta-blockers, long-acting nondihydropyridine calcium antagonists offer the benefits of heart rate reduction, as well as the vasodilation that is characteristic of the calcium antagonists as a class. This article reviews the data on risk reduction involving the beta-blockers and calcium antagonists, as well as other antihypertensive classes that have been shown to reduce the risk of cerebrovascular and cardiovascular disease. [ABSTRACT FROM AUTHOR]

Context: Despite evidence of efficacy of antihypertensive agents in treating hypertensive patients, safety and efficacy of antihypertensive agents for coronary artery disease (CAD) have been discerned only from subgroup analyses in large trials.Objective: To compare mortality and morbidity outcomes in patients with hypertension and CAD treated with a calcium antagonist strategy (CAS) or a non-calcium antagonist strategy (NCAS).Design, Setting, and Participants: Randomized, open label, blinded end point study of 22 576 hypertensive CAD patients aged 50 years or older, which was conducted September 1997 to February 2003 at 862 sites in 14 countries.Interventions: Patients were randomly assigned to either CAS (verapamil sustained release) or NCAS (atenolol). Strategies specified dose and additional drug regimens. Trandolapril and/or hydrochlorothiazide was administered to achieve blood pressure goals according to guidelines from the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) of less than 140 mm Hg (systolic) and less than 90 mm Hg (diastolic); and less than 130 mm Hg (systolic) and less than 85 mm Hg (diastolic) if diabetes or renal impairment was present. Trandolapril was also recommended for patients with heart failure, diabetes, or renal impairment.Main Outcome Measures: Primary: first occurrence of death (all cause), nonfatal myocardial infarction, or nonfatal stroke; other: cardiovascular death, angina, adverse experiences, hospitalizations, and blood pressure control at 24 months.Results: At 24 months, in the CAS group, 6391 patients (81.5%) were taking verapamil sustained release; 4934 (62.9%) were taking trandolapril; and 3430 (43.7%) were taking hydrochlorothiazide. In the NCAS group, 6083 patients (77.5%) were taking atenolol; 4733 (60.3%) were taking hydrochlorothiazide; and 4113 (52.4%) were taking trandolapril. After a follow-up of 61 835 patient-years (mean, 2.7 years per patient), 2269 patients had a primary outcome event with no statistically significant difference between treatment strategies (9.93% in CAS and 10.17% in NCAS; relative risk [RR], 0.98; 95% confidence interval [CI], 0.90-1.06). Two-year blood pressure control was similar between groups. The JNC VI blood pressure goals were achieved by 65.0% (systolic) and 88.5% (diastolic) of CAS and 64.0% (systolic) and 88.1% (diastolic) of NCAS patients. A total of 71.7% of CAS and 70.7% of NCAS patients achieved a systolic blood pressure of less than 140 mm Hg and diastolic blood pressure of less than 90 mm Hg.Conclusion: The verapamil-trandolapril-based strategy was as clinically effective as the atenolol-hydrochlorothiazide-based strategy in hypertensive CAD patients. [ABSTRACT FROM AUTHOR]

The present 2 multicenter studies were designed to evaluate whether patients with essential hypertension derived equal benefits from use of combination therapy with a calcium antagonist and angiotensin-converting enzyme (ACE) inhibitor as from doubling the dose of the calcium antagonist. After a 2-week washout and a 2-week single-blind placebo run-in period, a total of 1,390 patients were treated with either nifedipine 30 mg (study 1) or amlodipine 5 mg (study 2) once daily for 4 weeks. The 1,079 patients whose diastolic blood pressure remained between 95 and 115 mm Hg were randomized to 8 weeks of double-blind therapy with amlodipine 5 mg/benazepril 10 mg, amlodipine 5 mg/ benazepril 20 mg, nifedipine 30 mg or nifedipine 60 mg (study 1), and amlodipine 5 mg/benazepril 10 mg, amlodipine 5 mg/benazepril 20 mg, amlodipine 5 mg or amlodipine 10 mg (study 2). Both doses of the calcium antagonist/ACE inhibitor combination therapy lowered diastolic pressure as much as the high dose and significantly better than the lower dose of calcium antagonist monotherapy (with either nifedipine or amlodipine). However, 15% of patients in the nifedipine high-dose monotherapy group and 24% in the amlodipine high-dose monotherapy group presented with some form of edema. In contrast, the incidence of edema was similar for patients treated with both combination therapy and low-dose calcium antagonists. Thus, combination therapy with a calcium antagonist and an ACE inhibitor provides blood pressure control equal to that of high-dose calcium antagonist monotherapy but with significantly fewer dose-dependent adverse experiences such as vasodilatory edema. Inc. [ABSTRACT FROM AUTHOR]

Objective: To assess antihypertensive efficacy of beta-blockers and their effects on cardiovascular morbidity and mortality and all-cause morbidity compared with diuretics in elderly patients with hypertension.Data Source: A MEDLINE search of English-language articles published between January 1966 and January 1998 using the terms hypertension (drug therapy) and elderly or aged or geriatric, and cerebrovascular or cardiovascular diseases, and morbidity or mortality. References from identified articles were also reviewed.Data Selection: Randomized trials lasting at least 1 year, which used as first-line agents diuretics and/or beta-blockers, and reported morbidity and mortality outcomes in elderly patients with hypertension. DATA SYNTHESIS AND RESULTS: Ten trials involving a total of 16164 elderly patients (> or =60 years) were included. Two thirds of the patients assigned to diuretics were well controlled on monotherapy, whereas less than a third of the patients assigned to beta-blockers were well controlled on monotherapy. Diuretic therapy was superior to beta-blockade with regard to all end points and was effective in preventing cerebrovascular events (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.51-0.72), fatal stroke (OR, 0.67; 95% CI, 0.49-0.90), coronary heart disease (OR, 0.74; 95% CI, 0.64-0.85), cardiovascular mortality (OR, 0.75; 95% CI, 0.64-0.87), and all-cause mortality (OR, 0.86; 95% CI, 0.77-0.96). In contrast, beta-blocker therapy only reduced the odds for cerebrovascular events (OR, 0.75; 95% CI, 0.57-0.98) but was ineffective in preventing coronary heart disease, cardiovascular mortality, and all-cause mortality (ORs, 1.01, 0.98, and 1.05, respectively).Conclusions: In contrast to diuretics, which remain the standard first-line therapy, beta-blockers, until proven otherwise, should no longer be considered appropriate first-line therapy of uncomplicated hypertension in the elderly hypertensive patient. [ABSTRACT FROM AUTHOR]