Cardiovascular disease: Deadly for dialysis patients

Current treatment of dialysis patients with cardiovascular disease (CVD) is suboptimal, according to newly published guidelines by a work group of the National Kidney Foundation (NKF). Lack of evidence of treatment efficacy and exclusion of dialysis patients from major CVD clinical trials may have contributed to the problem.

In an effort to improve therapy for dialysis patients, the work group has analyzed and organized existing evidence on CVD diagnosis and treatment in these patients. Based on the data, the group concluded that all dialysis patients should be evaluated for CVD and treated accordingly. Treatment for CVD depends on the type of disease present, drug side effects and interactions, and the type of kidney disease involved. In many cases, said the work group, treatment of CVD in dialysis patients can follow guidelines established for the general population.

There are, however, problems unique to dialysis patients that must be considered when treating CVD. Certain hemodynamic factors must also be maintained. Dosages for drugs that are dialyzed or cleared renally must be carefully adjusted. Dosing intervals of some drugs need to be scheduled in order not to interfere with dialysis. Antihypertensives, for example, should be given at bedtime. "That's to prevent the possibility of a large decrease in blood pressure during dialysis the next day," said George Bailie, Pharm.D., Ph.D., professor of pharmacy at Albany College of Pharmacy.

The NKF guidelines for hypertension stated that patients 20 mm Hg or more over goal would probably need to start with both first- and second-line antihypertensives. Every CKD patient should be on an ACE inhibitor or an angiotensin receptor blocker (ARB), according to Bailie. These two classes of drugs have several benefits, he said. Most important, they decrease the progression of kidney disease.

Dialysis patients who have been diagnosed with coronary artery disease (CAD) should receive similar therapy to other CAD patients, said the work group. Therapy with aspirin, beta-blockers, nitroglycerin, statins, ACE inhibitors or ARBs, and calcium-channel blockers is appropriate for dialysis patients when indicated.

Clinicians may need to make adjustments in dosing or drug selection for CAD patients. Hypotension caused by nitrates, for example, can be potentiated by the hypovolemia that occurs after hemodialysis. Different drugs within the same class may vary greatly in individual hemodynamic and electrophysiological effects. Careful drug selection can minimize adverse reactions.

Because people on dialysis are already at increased risk for bleeding, anticoagulant therapy also needs special attention. The work group recommended following the American Heart Association stroke guidelines, as long as the increased risk for bleeding is taken into account. Careful monitoring and appropriate dose adjustments are required.

Circulating calcium levels may be elevated in people with CKD. Too much calcium can lead to calcium deposits in the soft tissues of the body, including veins and arteries. With an increase in coronary artery calcification, there is a much higher cardiovascular death rate, said Bailie. Therefore, controlling calcium levels and related factors can decrease the risk of cardiovascular death. Previously published NKF guidelines address this therapy in great detail. (See also "Coping with Chronic Kidney Disease" in the Sept. 27, 2004, issue of Drug Topics.)

"Pharmacists should know that CKD patients are at the highest risk for adverse cardiovascular outcomes," Bailie said. The most important points for R.Ph.s to glean from the new guidelines, he added, are that dialysis patients with CVD tend to be on several different medications, some drugs are contraindicated in patients on dialysis, and "tight control of blood pressure, lipids, and blood glucose is highly important."

More dialysis patients die from CVD than from any other complication, according to NKF. For children, the danger is especially grave. Pediatric patients on chronic dialysis are 1,000 times more likely to die from cardiovascular disease than the rest of the pediatric population.