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Therapeutics Letter, issue 8, July/August 1995

Drugs of Choice in the Treatment of Hypertension

(Part 2)

After review of the long term hypertension studies, including the epidemiologic and randomized placebo controlled drug trials, certain clinically important facts stand out:

 These facts suggest the following ways to assist in managing your patients with hypertension:

In Part 1 we summarized the published evidence demonstrating that if we want to be certain of reducing morbidity and mortality in our hypertensive patients, a low-dose thiazide diuretic is the best choice. However, we obviously need the use of more than one class of antihypertensive drugs. Beyond the thiazides, we have much less evidence of effectiveness in decreasing cardiovascular events. We cannot assume that drugs which are equivalent in lowering blood pressure will prove to be equally effective in reducing morbidity and mortality.

What is the evidence that beta blockers decrease morbidity and mortality in hypertensive patients?

There are only two trials in which the effectiveness of beta blockers (propranolol(3) and atenolol(7)) can be compared with placebo. When the data from these trials are combined, there is a trend towards a reduction in the incidence of total stroke, log odds ratio, 0.77 (0.59-1.04), but little effect on total coronary events, 0.89 (0.71-1.13). The lack of effectiveness of atenolol based therapy in reducing coronary events corroborates that seen in other studies. (8), (9) It may be that the high cardioselectivity of atenolol is not a desirable pharmacological action.

There are three trials(3), (7), (10) in which the effectiveness of beta blockers can be compared with thiazides. When the results of these trials are combined in a meta-analysis the patients receiving thiazide had a non statistically significant reduction in the incidence of stroke, 0.81 (0.58-1.14)and coronary events, 0.92 (0.74-1.14). In post myocardial infarction trials, non-selective beta blockers and high dose beta-1 selective blockers, but not oxprenolol or pindolol, beta blockers with high partial agonist (increased sympathomimetic) activity, reduce risk of reinfarction and mortality.(11) With the evidence presently available, it is advisable when prescribing beta blockers to use a non-selective beta blocker in the lowest dose required to lower the blood pressure (see Table).

In what hypertensive patient is a beta blocker the drug of first choice?

To lower blood pressure in patients with angina pectoris a beta blocker is the drug of first choice. Although we do not have the evidence, it also seems reasonable to use a beta blocker as first choice in patients where the drug can be used to treat more than the hypertension, eg. patients with frequent recurrent migraine or patients with sympathetic hyperactivity, resting tachycardia, and palpitations. Beta blockers should not be used in patients with asthma or other forms of obstructive airways disease.

Table 1: Beta Blockers

Beta Blockers Trade Name Usual Dosage Range Daily Cost (x)
Propanolol* Inderal®, generic
Inderal® LA
20-120 mg BID
60-240 mg daily
Nadolol* Corgard®, generic 20-160 mg daily $0.15-$0.79
Timolol* Blocadren®, generic 5-20 mg BID $0.36-$1.05
Atenololº Tenormin®, generic 25-100 mg daily $0.20-$0.66
Metoprololº Betaloc®, Lopressor®, generic
Betaloc® SR, Lopressor® SR
25-100 mg BID
100-200 mg daily
Acebutolol^ Sectral®, Monitan®, generic 100-400 mg daily $0.44-$1.32
Oxprenolol^ Trasicor®
Slow Trasicor®
20-160 mg BID
80-320 mg daily
Pindolol*^ Visken®, generic 5-15 mg BID $0.52-$1.31
Labetalol*ª Trandate® 100-400 mg BID $0.52-$1.82

* non-selective || º selective || ^ partial agonist || ª alpha blocker

(x) Average or lowest cost alternative (LCA) price in BC, 1994.

In what hypertensive patient is an ACE inhibitor the drug of first choice?

ACE inhibitors have been clearly shown to prolong survival in patients with congestive heart failure.(12) They are therefore the obvious first choice in patients with hypertension and CHF. It is not established at the present time whether ACE inhibitors have a unique renal protective effect in diabetic nephropathy.(13)

A recent study suggests that ACE inhibitors increase the risk of hypoglycemia in treated diabetic patients.(14) There are no proven therapeutic differences between the ACE inhibitors; drug choice can be made based on convenience and cost. (see Table). The cost can be minimized by prescribing 1/4 or 1/2 tablets whenever possible. (e.g.1/4 of a 20 or 40 mg tablet of quinapril costs $0.23 a day).

Table 2: ACE Inhibitors

ACE Inhibitors Trade Name Usual Dosage Range Daily Cost (x)
Capoten®, generic
5-40 mg daily
1.25-10 mg daily
12.5-50 mg daily
$0.92 all tablets
2-8 mg daily
5-40 mg daily
1-10 mg daily
Prinivil®, Zestril
5-40 mg daily
10-40 mg daily
5-40 mg daily

(x) Average or lowest cost alternative (LCA) price in BC, 1994.

In what hypertensive patient is a calcium antagonist the drug of first choice?

At the present time there are no outcome studies which identify a group of patients who would specifically benefit from a calcium antagonist. It is clear that post MI patients with left ventricular dysfunction do worse with diltiazem than with placebo.(15) An overview of 31 placebo controlled trials submitted to the United States Food and Drug Administration (16) reported that patients receiving calcium antagonists had a 63% excess of cardiac events, as compared to placebo.

A recent unpublished but highly publicized study also suggests that patients receiving a calcium antagonist for hypertension have a significantly increased risk of myocardial infarction compared with patients receiving diuretics or beta blockers. Neither of these studies are definitive. They do, however, reinforce the message in this and the previous letter, and emphasize the need for prospective randomized controlled studies measuring morbidity and mortality. These trials are under way, but we cannot expect any results for 4 - 5 years.

Table 3: Calcium Antagonists

Calcium Antagonists Trade Name Usual Dosage Range Daily Cost (x)
Diltiazem Cardizem®, generic
Cardizem SR®
Cardizem CD®
60-120 mg BID, TID
60-180 mg BID
120-300 mg daily
Verapamil Isoptin®, generic
Isoptin SR®
80-160 mg BID, TID
120-240 mg BID
120-480 mg daily
Nifedipine Adalat®, generic
Adalat PA®
Adalat XL®
5-30 mg BID, TID
10-30 mg BID
30-90 mg daily
Felodipine Plendil®, Renedil® 2.5-20 mg daily $0.54-$2.12
Amlodipine Norvasc® 5-10 mg daily $1.33-$1.94
Nicardipine Cardene® 20-40 mg TID $1.85-$3.70

(x) Average or lowest cost alternative (LCA) price in BC, 1994.

In what hypertensive patients are second drugs useful?

From the large controlled studies of the treatment of mild hypertension it is clear that in at least 50% of patients the BP can be controlled with a thiazide alone. The additional drugs used in these studies, for patients not controlled with a thiazide include reserpine in three studies, methyldopa in two studies, hydralazine in two studies, and beta blockers in two studies. We thus can have some confidence in the effectiveness of these drugs used in combination with a thiazide. In patients with moderate to severe hypertension 3 to 4 drugs are often required to adequately control the blood pressure. We, therefore, are fortunate to have a wide armamentarium of drugs to choose from (see Tables).


It is up to the clinician, through systematic therapeutic trials, to identify the drug(s) which are efficacious, well tolerated in low doses, convenient, and affordable to the patient and society. We should use the drugs proven to reduce morbidity and mortality as much as possible, but occasionally we are forced to individualize and choose based on other factors.

Table 4: Alpha 1 Blockers

Alpha 1 Blockers Trade Name Usual Dosage range Daily Cost (x)
Prazosin Minipress®, generic 1-10 mg BID $0.34-$1.32
Terazosin Hytrin® 1-20 mg daily $0.64-$2.94
Doxazosin Cardura® 1-16 mg daily $0.58-$3.60

(x) Average or lowest cost alternative (LCA) price in BC, 1994.

Table 5: Central and Peripheral Sympatholytics

Central and Peripheral Sympatholytics Trade Name Usual Dosage Range Daily Cost (x)
Reserpine Serpasil®, generic 0.0625-0.25 mg daily <<$0.01
Methyldopa Aldomet®, generic 125 mg - 1 g daily $0.08-$0.50
Clonidine Catapres®, generic 0.05-0.3 mg BID $0.20-$1.06

(x) Average or lowest cost alternative (LCA) price in BC, 1994.

Table 6: Direct Vasodilators

Direct Vasodilators Trade Name Usual Dosage Range Daily Cost (x)
Hydralazine Apresoline®, generic 25-100 mg BID $0.35-$1.08
Minoxidil Loniten® 2.5-40 mg daily $0.34-$2.96

  * Average or lowest cost alternative (LCA) price in BC, 1994.


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  13. Bauer JH. Diabetic Nephropathy: Can it be prevented? Are there renal protective antihypertensive drugs of choice? South Med. J. 1994; 87:1043-1052.

  14. Herings RMC, de Boer A, Stricker BHCh, et al. Hypoglycaemia associated with use of inhibitors of angiotensin converting enzyme inhibitors. Lancet 1995;345:1195-98.

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