Calcium Channel Blockers Can Trigger, Aggravate GERD

NEW YORK -- A diagnosis of hypertension is hard enough for many patients to swallow. But a lifetime of calcium channel blocker therapy can be difficult to stomach-literally.

Calcium channel blockers appear to trigger or aggravate gastroesophageal reflux disorder (GERD) and can be problematic for a significant minority of hypertensive patients, Aileen Luzier, Pharm.d., said at the annual meeting of the American Society of Hypertension. Other antihypertensive classes, including the [beta]-blockers, [alpha]-adrenergic agents, and angiotension II receptor blockers can also aggravate GERD, but this phenomenon is most strongly associated with the calcium channel blockers.

Dr. Luzier of the School of Pharmacy at the State University of New York at Buffalo based her conclusions on a study of the use of acid-suppressing drugs during 1 year in a cohort of 20,615 hypertensive patients, all of whom were members of a Buffalo-area managed care organization. All of these subjects, who had a mean age of 65 years, were taking at least one antihypertensive drug. All major classes of antihpertensives were represented.

Diuretics were the most commonly used agents, taken by 39% of the patients. These were followed by ACE inhibitors (31%), [beta]-blockers (29%), and calcium channel blockers (CCBs) (24%). Only 9% of patients took [alpha]-agonists, and 3% took angiotensin II receptor blockers. Less than 1% were using vasodilators, Dr. Luzier reported in a poster.

Overall, 16% of the 8,841 men and 19% of the 11,774 women were using some form of acid-suppression therapy Dr. Luzier and her associates calculated the odds ratios of acid-suppressant use for various classes of antihypertensives.

The diuretics and ACE inhibitors were essentially neutral, with an odds ratio of 1 for the use of acid suppressants. The [beta]-blockers had an odds ratio of 1.13; slightly higher were the angiotensin II receptor blockers, with an odds ratio of 1.19. The two classes most associated with the use of acid suppressants were the [alpha]-blockers, with an odds ratio of 1.24, and the CCBs, at 1.48. Dr. Luzier said that 26% of patients on CCBs were also on acid-suppressing drugs, compared with an average of 17% for the other antihypertensive categories. She added that the investigators controlled for the use of a wide range of other drugs for noncardiovascular indications.

Looking more closely at the CCBs as a class, the investigators found that diltiazem had the highest odds ratio (1.74) for concurrent use of acid suppressants. This was followed by amlodipine (1.64), nifedipine (1.32), and verpamil (1.29).

These findings are not entirely surprising, Dr. Luzier said. From a physiologic viewpoint, the association makes sense. "Calcium channel blockers are excellent smooth muscle relaxers. They relax the smooth muscle of the vasculature, which accounts for their vasodilatory effects. But this action is nonspecific; the drug does not know which muscles it is acting on. So, in addition to relaxing vascular smooth muscle, CCBs also relax the lower esophageal sphincter, which can precipitate or aggravate GERD."

The [alpha]-blockers, [beta]-blockers, and angiotensin II receptor blockers also relax smooth muscle but do not seem to affect esophageal sphincter tone to the same degree as the CCBs.

This is not the first time an association between CCBs and GERD has been reported. In an interview, Dr. Luzier said she and her colleagues were motivated to look into this issue after a study of 150 normal volunteers showed a 50% increase in esophageal symptoms following initiation of CCBs. Nifedipine has been previously reported to reduce the lower esophageal sphincter tone by 24%-30%, in a dose-dependent manner. Verapamil has also been shown to reduce esophageal sphincter tone by about one-third in healthy volunteers.

Dr. Luzier estimated that in practice about 10% of patients taking CCBs have a noticeable onset of reflux symptoms or an increase in such symptoms; it is probably more common in those who already have histories of reflux.

But she believes it is an important issue to consider when planning treatment. Combining antihypertensive classes could have an additive effect, refluxwise, if the combination regimen includes a CCB along with another sphincter-relaxing agent such as an [alpha]-adrenergic agent. And it may be more of an issue if a patient has preexisting asthma, which is associated with an increase in GERD.

Dr. luzier estimated that a patient with asthma who is on a combination of a CCB and [alpha]-adrenergic antihypertensives has an odds ratio of 3.25 for needing an acid suppressant as well.

Reflux may reduce compliance and defeat the purpose of hypertensive therapy. And "if you use CCBs and you end up having to add a proton pump inhibitor or an [H.sub.2] antagonist, you really increase the overall cost," he said.