Drug Update: Calcium Channel Blockers for Hypertension - Brief Article

0 Comments | Family Practice News, April 1, 2000 | by Mitchel L. Zoler

After a rocky stretch 5 years ago, calcium channel blockers have regained their role as an important option for treating hypertension.

In the mid-1990s, the results from a few epidemiologic studies raised questions about the safety of calcium channel blockers (CCBs) in patients with coronary artery disease. Today most experts agree that treatment with a short-acting calcium channel blocker does pose a risk of adverse cardiovascular effects, and therefore short-acting formulations have largely been abandoned. But extended-release formulations and the CCBs that are naturally long acting are generally considered safe. Fears of an increased risk of cancer or of bleeding with CCB use have largely fallen by the wayside.

Expert opinion differs regarding the role of CCBs for treating hypertension. The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (the most recent version of the official U.S. hypertension treatment recommendations) puts [beta]-blockers and diuretics first among the blood pressure-lowering drugs. The other classes, including CCBs, are recommended as first-line agents when there is a compelling medical reason to use them. For hypertensive patients with the most common comorbidities, this strategy usually means using an angiotensin-converting enzyme (ACE) inhibitor.

The biggest role for CCBs is for salt-sensitive, low-renin hypertensive patients, which usually means elderly and African American patients. Some experts prefer to start with a diuretic in these patients; others pick a CCB because, they say, it has a better safety profile. Others who might start on a CCB include those with isolated systolic hypertension and a contraindication for a diuretic; angina or another manifestation of ischemic heart disease; hypertrophic cardiomyopathy; or diastolic dysfunction.

CCBs pair well with several other drug classes. The most popular partner is an ACE inhibitor, which can reduce the pedal edema often caused by CCBs. Another useful pairing is a dihydropyridine CCB with a [beta]-blocker. Pairing a CCB with a diuretic is possible, but they must be combined cautiously since using a CCB in a dehydrated patient may increase the risk of a cardiovascular event triggered by elevated sympathetic tone.

When using CCBs, the recommended dosage scheme is "start low and go slow" especially in the elderly. Experts advise against increasing the starting dose by much for any patient. If the CCB is unable to fully control blood pressure at a moderate dose, add a new agent rather than increasing the CCB dose. CCBs are metabolized by the liver; in patients with moderate to severe hepatic insufficiency, keep the dose low The dihydropyridine CCBs can be used during pregnancy, but verapamil and diltiazem should be avoided because they slow fetal heart rates. The CCBs pass into breast milk and so should be avoided in breast-feeding women.

DIHYDROPYRIDINES

These drugs are free of negative chronotropic effects, so they can be used in patients with left ventricular dysfunction or electrical heart disturbances. These medications pair better with [beta]-blockers than do the nondihydropyridines. All drugs in this subclass cause pedal edema, which is generally harmless but may be a cosmetic concern. They also can cause palpitations, flushing, and tachycardia, but these effects are minimized by using long-acting formulations. Use a nondihydropyridine for patients with ischemic disease or angina. When CCBs are used as monotherapy, some also think that nondihydropyridines have an edge. For patients already on an ACE inhibitor or a [beta]-blocker, a dihydropyridine is a good second-line drug. These drugs have no positive effect on proteinuria, unlike the nondihydropyridines. The dihydropyridines increase sympathetic neural tone. Be alert for patients who drink a relatively large amount of grapefruit juice, which will increase the bioavailability of dihydorpyridines and t herefore enhance their effect. Many experts see little basis for choosing among the drugs in this subclass.

A seventh dihydropyridine, nimodipine, is licensed for use in the United States, but it is labeled for subarachnoid hemorrhage only, not for hypertension.

DRUG                      DOSAGE              COST/DAY [*]
amlodipine besylate       2.5-10 mg once      $1.32 (5 mg)
 (Norvasc)                daily
felodipine                2.5-10 mg once      $0.96 (5 mg)
 (Plendil)                daily
isradipine                5-20 mg once daily  $1.22 (5 mg)
 (DynaCirc CR)
nicardipine hydrochloride 30-60 mg twice      $1.40 (30 mg
(Cardene SR)              daily               twice daily)
nifedipine                30-120 mg once      $1.38 (30 mg)
 (Procardia XL)           daily
nisoldipine               20-40 mg once daily $0.93 (20 mg)
 (Sular)
DRUG                      COMMENT [ ]
amlodipine besylate       Has specifically been shown to cut mortality due
 (Norvasc)                to nonischemic causes in patients with heart
                          failure when used with an ACE inhibitor. Some
                          experts prefer amlodipine because they believe
                          that its naturally long half-life produces the
                          smoothest effect over 24 hours, but others say
                          that any dihydropyridine in an extended-release
                          formulation has similar effects. Usual starting
                          dosage is 5 mg once daily. Also labeled for
                          treating angina.
felodipine                Labeled for hypertension only. Usual starting
 (Plendil)                dosage is 5 mg once daily.
isradipine                Labeled for hypertension only.
 (DynaCirc CR)
nicardipine hydrochloride Only sustained-release CCB that requires twice-
(Cardene SR)              daily dosing. Labeled  for hypertension only.
nifedipine                Also labeled for treating angina.
 (Procardia XL)
nisoldipine               Labeled for hypertension only.
 (Sular)