VOLUME 33 : NUMBER 4 : August 2010
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The decision on when to start drugs for the treatment of elevated blood pressure should be determined by an individual's absolute risk of having an adverse cardiovascular event. The choice of drug depends on its safety and effectiveness and its indications and contraindications for individual patients. Most patients will require two or more drugs to reach their target blood pressure.The main classes of antihypertensive drugs are equally effective at reducing blood pressure, but beta blockers are no longer recommended as first-line treatment for most patients.
Key words: antihypertensives, cardiovascular disease, hypertension.
Aust Prescr 2010;33:108-12
All patients with elevated blood pressure should be encouraged to have a healthy lifestyle.1 Although there are benefits from weight loss, salt and alcohol reduction and exercise, these lifestyle changes may be insufficient to control a patient's blood pressure. This leaves them at risk of coronary heart disease, stroke and renal failure. If the high blood pressure is confirmed by accurate measurements on several occasions, drug treatment should be considered.
Who should receive drug therapy?
Drug treatment for elevated blood pressure should not be based solely on accurate blood pressure readings. It should also consider an individual's absolute cardiovascular risk – their risk of having a stroke or myocardial infarction over a specified period of time, usually five years.2 An absolute risk calculator can be used to identify who is most likely to benefit from treatment.3 The previous underestimation of risk in Aboriginal and Torres Strait Islander people by such calculators has been addressed in the recently published Australian risk calculator.4–6
Immediate treatment to lower blood pressure is recommended for patients with confirmed hypertension (multiple measures on at least two separate occasions):
Patients with associated conditions (for example, stroke or myocardial infarction) or evidence of end-organ damage (for example, microalbuminuria, left ventricular hypertrophy) also need urgent treatment (Fig. 1).
Starting drug therapy
Once the decision has been made to start drug therapy, the choice of antihypertensive drug should be based on the patient's age and the presence of associated clinical conditions or end-organ damage. The presence of other diseases may favour or limit the use of particular drug classes and there may be potential interactions with other drugs (Table 1). Cost and the ease of adhering to treatment should also be considered. Antihypertensive drugs in different classes have similar efficacy. In uncomplicated cases the recommendation is to start with an angiotensin-converting enzyme (ACE) inhibitor, angiotensin receptor antagonist, calcium channel blocker or diuretic (in the aged).2 Beta blockers are no longer recommended as first-line treatment for uncomplicated high blood pressure as meta-analyses show they have an adverse relative risk of stroke and new onset diabetes compared to other drugs.78
Target blood pressure
A patient's comorbidity helps to determine which blood pressure to aim for. In uncomplicated hypertension the target should be 140/90 mmHg or lower if tolerated. The target is under 130/80 mmHg in patients with end-organ damage or conditions such as diabetes, and under 125/75 mmHg in patients with proteinuria (>1 g/day).
It is important that patients be treated to reach their recommended blood pressure. Failure to do so leaves patients at significant residual adverse risk.
Start with the lowest recommended dose of the selected drug and review the patient after six weeks. If the drug is not well tolerated or is ineffective, change to a drug of a different class. If the target blood pressure is still not reached, add a further drug from a different pharmacological class at a low dose, rather than increasing to the maximum dose of the first drug.
This treatment approach maximises efficacy while minimising adverse effects. Titrate the dose of one drug then the other until the target blood pressure is reached. Additional drugs may be required.
Attaining and maintaining the target blood pressure may be assisted by:
Recommended and discouraged drug combinations for hypertension 2
or angiotensin receptor antagonist
|plus||calcium channel blocker||Diabetes or dyslipidaemia|
|plus||thiazide diuretic||Heart failure or post stroke|
|plus||beta blocker||Post myocardial infarction or heart failure|
|Beta blocker||plus||dihydropyridine calcium channel blocker||Coronary heart disease|
|Thiazide diuretic||plus||calcium channel blocker|
|plus||beta blocker||Not with glucose intolerance, metabolic syndrome or diabetes|
|Combinations to avoid||Recommendation|
or angiotensin receptor antagonist
|plus||potassium-sparing diuretic||Avoid because of risk of hyperkalaemia|
|Verapamil||plus||beta blocker||Avoid because of risk of heart block|
|ACE inhibitor||plus||angiotensin receptor antagonist||In a large trial, combination therapy did not reduce cardiovascular death or morbidity in patients with vascular disease or diabetes while increasing the risk of hypotensive symptoms, syncope and renal dysfunction|
ACE angiotensin-converting enzyme
Approximately 60% of patients with elevated blood pressure will not achieve their blood pressure targets with monotherapy. Most patients will require a combination of two or more drugs to achieve adequate blood pressure control. There are several effective combinations (Table 2). In the ACCOMPLISH trial an ACE inhibitor and calcium channel blocker combination reduced cardiovascular events more than a combination of the ACE inhibitor with a diuretic.9
Long-term drug treatment
Drug treatment is usually lifelong, as age is the most important determinant of adverse risk, unless the blood pressure is well controlled by profound lifestyle changes.10 If blood pressure is normal and stable, the interval between visits can be lengthened, for example, review every three months for the next 12 months and six-monthly thereafter.
If treatment is stopped, the patient's blood pressure should be checked regularly. Patients should continue the lifestyle changes and agree to resume drug treatment if their blood pressure rises again.
Resistant blood pressure
Failure to control blood pressure can be due to a wide range of prescriber, patient, healthcare system and drug related factors. If blood pressure remains above the target despite maximal doses of at least two appropriate drugs after a reasonable period, consider the following potential explanations:
Drug treatment in older people
In the elderly, isolated elevated systolic blood pressure is more prevalent due to large vessel stiffness associated with ageing. Calcium channel blocker- or diuretic-based drug treatment is recommended.
In the very elderly, the recommended blood pressure targets may be difficult to achieve due to comorbidity, reduced physiological function and polypharmacy. However, the elderly are most at risk of adverse cardiovascular events and trials have shown that drug therapy is just as effective in advanced age. The HYpertension in the Very Elderly Trial (HYVET) studied patients aged 80 years or more (mean age 83.6 years). It showed a 39% relative reduction in the rate of death from stroke, a 21% reduction in the rate of death from any cause, a 23% reduction in the rate of death from cardiovascular causes and a 64% reduction in the rate of heart failure for those on active treatment versus placebo. Fewer serious adverse events were reported in the active treatment group so concerns about causing more harm than good are allayed.11
Drug therapy is warranted in individuals with a high risk of adverse cardiovascular events. It does not obviate the need for behavioural modification. All classes of antihypertensive drugs have similar efficacy, but specific recommendations are made according to the patient's characteristics. Whichever drug is started, it is important to treat until the target blood pressure is reached. Usually more than one drug is required to reach the target.
Professor Nelson has participated in trials that have received funding from SmithKline Beecham, AstraZeneca, Bayer, Sanofi-Aventis, Merck Sharpe and Dohme, Pfizer, Servier Laboratories and Bristol-Myers Squibb. He has served on advisory boards for Sanofi-Aventis, Novartis, Schering-Plough and Solvay Pharmaceuticals, prepared educational material for Servier Laboratories, AstraZeneca and Bristol-Myers Squibb and received conference and travel support from Bayer HealthCare AG, Novartis and Sanofi-Aventis.
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