Thiazides are considered to be appropriate initial treatment for most people with hypertension. Choice of other antihypertensives, including calcium channel blockers, is decided on an individual basis.
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Key points
- Thiazides are appropriate initial therapy for most people with hypertension.
- Choice of other antihypertensives is decided by individual patient factors.
- Factors which potentially favour use of calcium channel blockers include arrhythmia (verapamil only), angina, older
age and high risk of stroke.
- Factors which may weigh against the use of calcium channel blockers include potential drug interactions, and diltiazem
and verapamil are contraindicated in heart block and heart failure.
- Choice between the different calcium channel blockers depends on patient tolerability, co-morbidity and drug interactions.
Factors favouring use of calcium channel blockers:
- Hypertension with co-morbid angina
- Hypertension with co-morbid arrhythmia (verapamil only)
- Elderly people
- People with an increased risk of stroke
- Verapamil and diltiazem may be alternatives to beta blockers for secondary prevention post myocardial
infarction if beta blockers are contraindicated or not tolerated.2
|
Thiazides are appropriate initial therapy for most people with hypertension
There is limited evidence of superiority of one antihypertensive over another but evidence suggests that for most patients,
diuretics can be considered first, based on their effectiveness, safety and low cost.
Choice of additional antihypertensives is decided by individual patient factors
Other agents may be chosen for individual patients based on concurrent medical conditions, patient tolerability and
drug interactions. Indications for treatment with different antihypertensive agents are discussed in BPJ
6 (June 2007).
Factors for and against the use of calcium channel blockers
Factors that potentially favour the use of calcium channel blockers include arrhythmia (verapamil only), angina, or
high risk of stroke. Verapamil can also be used post myocardial infarction if beta blockers are contraindicated or not
tolerated. In addition, calcium channel blockers may be more suitable than other agents for elderly people and those of
African descent.1
There is some evidence of a superior protective effect of calcium channel blockers in people with a high risk of stroke
when compared with other antihypertensives.2
Calcium channel blockers have a favourable effect for treating hypertension with co-existing angina. Verapamil may have
a favourable effect when co-existing arrhythmia is present.
Age and ethnicity have less influence on the antihypertensive effect of calcium channel blockers compared with other
agents (e.g. ACE inhibitors) and this may present a benefit for calcium channel blocker use in elderly patients.2 The
National Institute for Health and Clinical Excellence (NICE) issued an updated hypertension guideline in June 2006 which
states that calcium channel blockers are a first line alternative to thiazide diuretics in hypertensive patients over
55 years.3
Factors, which may weigh against the use of calcium channel blockers include potential drug interactions, and diltiazem
and verapamil are contraindicated in heart block and heart failure.
Choice between calcium channel blockers
Few studies have directly compared calcium channel blockers and choice may be largely based on patient tolerability,
co-morbidity and interaction profile.
| Isradipine and MIDAS study concerns.
The MIDAS study published in 1996 was designed to compare the effects of normal release (short acting) isradipine
with hydrochlorothiazide on atherosclerosis progression in patients with hypertension. An incidental finding was the
higher rate of major cardiovascular events in the isradipine group compared with the hydrochlorothiazide group (25/442
vs 14/441; P= 0.07). Apart from not reaching statistical significance other factors mitigate against concerns about
the use of Dynacirc SRO for hypertension. Firstly, MIDAS was not designed to detect differences in clinical events
or outcomes and these findings were incidental. Secondly in MIDAS, normal release isradipine (short acting) was given
twice daily and in general short acting dihydropyridines (including nifedipine) have been associated with increased
cardiovascular events in several trials and meta-analyses. Dynacirc SRO is formulated to provide a long duration of
action similar to felodipine. Subsequent studies using longer-acting calcium channel blockers have shown better cardiovascular
outcomes compared with shorter-acting agents. |
Calcium channel blockers vary in their site of action and therapeutic effect
All calcium channel blockers block the inward flow of calcium ions into cells in vascular smooth muscle, myocardial
cells, and cells within the sino-atrial (SA) and atrioventricular (AV) nodes.
Dihydropyridines (amlodipine, felodipine, isradipine, and nifedipine) act mainly on vascular smooth muscle and have
minimal effect on normal myocardial cells; therefore their main effect is vasodilation. Their minimal effect on the SA
or AV nodes means they are not rate-limiting agents.
The dihydropyridines are mainly used for hypertension and angina and common side effects are associated with vasodilatation,
such as flushing, headache, and ankle swelling.
Benzothiazepines (diltiazem) and phenylalkylamines (verapamil) have less selective effect on vascular smooth muscle
and have greater cardiac effects. They act on the myocardium to reduce contractility and heart rate and are used in angina
and hypertension, but should not be used in heart failure. Verapamil has greater selectivity for cardiac tissue than diltiazem
and therefore has more cardiac effects and is also used for arrhythmias.4, 5, 6
Choice of dihydropyridine may depend on patient preference
The dihydropyridines are similar in therapeutic effect and the choice between them may depend on patient preference.
Long-acting preparations are preferred to short-acting agents which can cause reflex tachycardia and are not suitable
for long term treatment of hypertension. Dihydropyridines are either formulated as long-acting preparations such as felodipine,
isradipine or nifedipine or inherently long acting such as amlodipine.
Rate-limiting calcium channel blockers may be chosen based on co-morbid conditions
Verapamil and diltiazem are also indicated for use in hypertension and can be considered in patients who have co-existing
conditions that would benefit from these agents such as verapamil in patients with co-existing arrhythmias. They are not
appropriate in heart failure or heart block, although dihydropyridines can be used with these conditions.
Verapamil and diltiazem are also associated with a number of drug interactions. Co-administration with simvastatin may
significantly increase the plasma concentration of simvastatin and potentiate the risk of statin-induced myopathy. Verapamil
also significantly increases the plasma concentration of atorvastatin when used in combination. These reactions are less
likely with the dihydropyridine group of calcium channel blockers and this should be considered when selecting a calcium
channel blocker.
Review concurrent drug therapy when implementing any of the calcium channel blockers.
COMPARISON OF CALCIUM CHANNEL BLOCKERS
Adapted from Lusher7 and Thomas.8
| Drugs |
Group |
Indications |
Special considerations |
Major adverse effects |
Comments |
Amlodipine
Felodipine
Isradipine
Nifedipine
|
Dihydropyridines
Greater vascular than cardiac tissue selectivity |
Hypertension
Angina (except isradipine which is only indicated for hypertension)
|
Less drug interactions with this group but some are significant including the interaction
with grapefruit juice |
Flushing
Oedema
Postural hypotension
Headache
|
Similar efficacy to thiazides
Recent studies suggest favourable effect in reducing stroke
May be beneficial for elderly |
| Diltiazem |
Benzothiazepine
Equal vascular and cardiac tissue selectivity |
Angina
Hypertension
|
Contraindicated in heart block & heart failure |
Bradycardia
Heart block
|
Caution required when used in combination with beta-blocker
|
| Verapamil |
Phenylalkylamine
Vascular tissue selectivity less or equal to cardiac |
Angina
Hypertension
Arrhythmias
Post MI if beta-blockers are unsuitable
|
Contraindicated in combination with a beta-blocker and in heart block & heart failure
|
Bradycardia
Heart block
Constipation
|
May be suitable for patients with ischaemic heart disease who are unable to tolerate
beta-blockers
|
References
- Grossman E, Messerli F. Calcium Antagonists. Prog Cardiovasc Dis 2004; 47 (1): 34-47
- Epstein B, Vogel K, Palmer B. Dihydropyridine Calcium Channel Antagonists in the Management of Hypertension. Drugs
2007; 67 (9): 1309-1327
- National Institute for Health and Clinical Excellence. Clinical Guideline: Hypertension: Management of hypertension
in adults in primary care. June 2006. http://www.nice.org.uk/nicemedia/pdf/HypertensionGuide.pdf Accessed
October 2007.
- Australian Medicines Handbook. Australian Medicines Handbook Pty Ltd. July 2006
- British National Formulary (BNF). BMJ Publishing Group and Royal Pharmaceutical Society of Great Britain. September
2007
- Sweetman SC (Ed), Martindale: The Complete Drug Reference. London: Pharmaceutical Press. Electronic version, (Edition
2007).
- Luscher T, Cosentino F. The Classification of Calcium Antagonists and their Selection in the Treatment of Hypertension.
Drugs 2006; 55 (4): 509-517
- Thomas S. Hypertension. In: Walker R, Whittlesea C, editors. Clinical Pharmacy and Therapeutics (4th Ed.) Edinburgh:
Churchill Livingstone Elsevier, 2007: 265-279