Blood pressure reduction

An effective HE or cost-effectiveness analysis is designed to answer certain questions, such as Is the treatment effective What will it cost and How do the gains compare with the costs By combining answers to all of these questions, the technique helps decision makers weigh the factors, compare alternative treatments, and decide which treatments are most appropriate for specific situations. Typically, one chooses the option with the least cost per unit of measure gained the results are represented by the ratio of cost to effectiveness (C E). With this type of analysis, called a cost-effectiveness analysis (CEA), various disease end points that are affected by therapy (risk markers, disease severity, death) can be assessed by corresponding indexes of therapeutic outcome (mmHg blood pressure reduction, hospitalizations averted, life years saved, respectively). It is beyond the scope of this chapter to elaborate further on principles of cost-effectiveness analyses. A number of references are available for this purpose [11-13]. 

Fischberg GM, Lozano E, Rajamani K, Ameriso S, Fisher MJ. Stroke precipitated by moderate blood pressure reduction. J Emerg Med 2000 19 339-346. 

Oliveira-Filho J, Silva SC, Trahuco CC, Pedreira BB, Sousa EU, Bacellar A. Detrimental effect of blood pressure reduction in the first 24 hours of acute stroke onset. Neurology 2003 61(8) 1047-1051. 

Therapeutic lifestyle modifications consisting of nonpharmacologic approaches to blood pressure reduction should be an active part of all treatment plans for patients with hypertension. The most widely studied interventions demonstrating effectiveness include ... 

Exercise facilitates both weight loss and blood pressure reduction. In addition, regular exercise improves functional capacity and symptoms in chronic stable angina.1 Once drug therapy for IHD is instituted, patients should be encouraged... 

Blood pressure reduction may be particularly pronounced after initiation and dose titration of 3-blockers that also possess a-blocking effects (e.g., labetalol and carvedilol). 

The nondihydropyridine calcium channel blockers have been shown to also decrease protein excretion in patients with diabetes,20 but the reduction in proteinuria appears to be related to the reductions in blood pressure. The maximal effect of nondihydropyridine calcium channel blockers on proteinuria is seen with a blood pressure reduction to less than 130/80 mm Hg and no additional benefit is seen with increased doses. Dihydropyridine calcium channel blockers, however, do not have the same effects on protein excretion, and may actually worsen protein excretion.17... 

Because of their reflex cardiac effect, vasodilators, if used alone in the treatment of hypertension, have not been a successful therapeutic tool. However, the reflex tachycardia and increase in cardiac output can be effectively blocked by the therapeutic association with a sympathetic blocker guanethidine, reserpine, methyldopa, or clonidine. More specifically, blockade of the cardiac beta-adrenergic receptors will also prevent the cardiac response to hydralazine. Thus, the therapeutic combination of hydralazine and propranolol can be successfully employed for effective blood pressure reduction(11). 

The blood pressure reduction by the diuretic agents occurs equally in supine, sitting and standing positions, at rest and during exercise. There is no orthostatic hypotension(13,14). 

In CEA, the total cost and the total benefits, measured in terms of an efficacy parameter, associated with two or more treatment pathways are added, and the increment is calculated. The incremental costs are then compared (in a ratio) with incremental outcomes (as measured in physical or natural emits). Physical and natural units can include both intermediate (surrogate) clinical endpoints (e.g. millimetres of mercury blood pressure reduction, changes in FEVi) or final endpoints (e.g. deaths averted or life-years gained). In a study that assessed the cost per deaths due to pulmonary embolism averted, Hull and associates reported that subcutaneous administration of... 

Initial dosage - 100 mg/day in single or divided doses, used alone or added to a diuretic taken with or immediately after meals. The dosage may be increased at weekly (or longer) intervals until optimum blood pressure reduction is achieved. 

Initial dose 40 mg once daily, alone or in addition to diuretic therapy. Gradually increase dosage in 40 to 80 mg increments until optimum blood pressure reduction is achieved. 

For initial therapy, start with the 0.1 mg system. If, after 1 or 2 weeks, desired blood pressure reduction is not achieved, add another 0.1 mg system or use a larger system. Dosage greater than two 0.3 mg systems usually does not improve efficacy. Note that the antihypertensive effect of the system may not commence until 2 to 3 days after application. Therefore, when substituting the transdermal system in patients on prior antihypertensive therapy, a gradual reduction of prior drug dosage is advised. Previous antihypertensive treatment may have to be continued, particularly in patients with severe hypertension. 

Hypertension - Administer with or without food. The usual recommended starting dose is 16 mg once daily when used as monotherapy in patients who are not volume-depleted. Candesartan can be administered once or twice daily with total daily doses ranging from 8 to 32 mg. Most of the antihypertensive effect is present within 2 weeks maximal blood pressure reduction generally is obtained within 4 to 6 weeks of treatment. 

Note Doses greater than 25 mg/day are likely to potentiate potassium excretion but provide no further benefit in sodium excretion or blood pressure reduction. 

The value of diuretics lies in their ability to reverse the Na retention commonly associated with many antihypertensive drugs that probably induce Na retention and fluid volume expansion as a compensatory response to blood pressure reduction. 

C. Ginkgo would be the most likely herbal treatment to benefit this patient, since it would improve cerebrovascular blood flow and cognitive function. Vertigo and tinnitus may also respond, although there is more evidence for the former. GarUc is traditionally used for cardiovascular benefits (Upid, blood pressure reduction), but it would be unlikely to produce immediate results. Peppermint is used as an antispasmodic in irritable bowel syndrome, while ginger tea is a common carminative (gas reducer) and motion sickness treatment. Valerian is useful as a sedative. 

Doses above 250 mg provide no further blood pressure reduction, but are more likely to induce metabolic disturbance (hypokalemia, hyperuricemia, etc.)... 

Most cardiovascular reflexes remain intact after administration of methyldopa, and blood pressure reduction is not markedly dependent on posture. Postural (orthostatic) hypotension sometimes occurs, particularly in volume-depleted patients. One potential advantage of... 

Fenoldopam is rapidly metabolized, primarily by conjugation. Its half-life is 10 minutes. The drug is administered by continuous intravenous infusion. Fenoldopam is initiated at a low dosage (0.1 mcg/kg/min), and the dose is then titrated upward every 15 or 20 minutes to a maximum dose of 1.6 mcg/kg/min or until the desired blood pressure reduction is achieved. 

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