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Feature Article

Study strengthens case against ACE inhibitors for certain heart patients

According to the Centers for Disease Control, coronary heart disease is the leading cause of death in the United States for both men and women. i A new study by VA researchers and researchers with the Baylor College of Medicine, St. Luke's Episcopal Hospital, and the Texas Heart Institute has called into question a therapy that's often used to treat patients with this illness: the use of angiotensin-converting enzyme (ACE) inhibitors in those about to undergo bypass surgery.

ACE inhibitors treat congestive heart failure and high blood pressure. They are also prescribed for certain kinds of kidney problems, especially for those with diabetes. These medications work by blocking an enzyme in the body that is responsible for causing blood vessels to narrow. If the blood vessels are relaxed, blood pressure is lowered, and more oxygen-rich blood can reach the heart. They also lower the amount of salt and water in the body, which also helps to lower blood pressure.

Some patients take ACE inhibitors over many years. The medication is also sometimes prescribed for patients who are about to undergo a procedure called coronary artery bypass grafting (CABG), a type of surgery that improves blood flow to the heart in patients with severe coronary heart disease. In coronary heart disease, a waxy substance called plaque builds up inside of the coronary arteries, which supply oxygen-rich blood to the heart. In CABG surgery, a healthy artery or vein is taken from the body and grafted to the coronary artery in order to bypass a blocked portion of the artery.

Many studies have shown that the long-term use of ACE inhibitors can help reduce illness and death in patients with coronary artery disease. Some patients, however, still require bypass surgery—and for them, use of the medication at the time of bypass surgery may cause problems.

"The role of ACE inhibitors in the preoperative setting and their effects on postoperative outcome is controversial," said Salim S. Virani, MD, PhD, a staff cardiologist and investigator at the Michael E. DeBakey VA Medical Center in Houston, Texas, and an assistant professor at Baylor College of Medicine. "We wanted to find out if patients on ACE inhibitors had more major adverse events immediately after CABG surgery."

The study team looked at the health records of nearly 9,000 patients who underwent isolated coronary artery bypass grafting (CABG without any additional procedures taking place at the same time) at Houston's St. Luke's Episcopal Hospital from Jan. 1, 2000, through July 31, 2011. They found that 45 percent of those patients had been on ACE inhibitors before surgery and 55 percent had not.

The team reviewed these records to determine the percentage of patients who had major adverse events immediately following surgery. These events included death, renal dysfunction (kidney problems), heart attacks, strokes, and atrial fibrillation (an irregular and often rapid heart rate.)

Their results were published in the June 20, 2012, edition of the American Journal of Cardiology. ii The researchers found that patients who had used ACE inhibitors before surgery were more likely than those who had not to have had problems following surgery. While heart attacks and strokes occurred in the same percentages for both groups, those taking ACE inhibitors had a significantly higher risk of problems involving renal dysfunction and atrial fibrillation after bypass surgery.

In all, 38.1 percent of patients who had used ACE inhibitors had some level of adverse event or events immediately following surgery, compared to 33.6 percent of those who did not use this type of medication. The study did not show any statistically significant difference in the levels of death following the surgery among the patients whose records were reviewed.

"We conclude that preoperative ACE inhibitor use is associated with an increased risk of major adverse events after coronary artery bypass grafting—in particular post-operative renal dysfunction and atrial fibrillation," said Salman J. Bandeali, MD, the first author of the study.

"It is important to note," Virani added, "that this study did not evaluate patients with congestive heart failure, who have been shown to benefit from ACE inhibitors in multiple studies."

Among the brand names for ACE Inhibitors in the United States are Accupril (quinapril), Aceon (perindopril), Altace (ramipril), Capoten (captopril), Lotensin (benazepril), Mavik (trandolapril), Monopril (fosinopril), Prinivil (lisinopril), Prinzide (lisinopril with a diuretic), Univasc (moexipril), Vaseretic (enalapril with a diuretic), Vasotec (enalaprilat, enalapril), Zestoretic (lisinopril with a diuretic), and Zestril (lisinopril).

Heart failure is a common chronic disease marked by frequent exacerbations often resulting in hospitalization and death. VA research's goal is to improve survival and quality of life for all VA patients with heart failure and those at risk for heart failure by decreasing hospitalization rates; improving the use of life-prolonging therapies; improving the use of therapies that improve the quality of life for Veterans with heart disease; empowering patients and caregivers to self-manage their condition; and improving the appropriateness of heart failure treatments and tests.

i AM Mini�o, SL Murphy, J Xu, KD Kochanek. Deaths: Final data for 2008. National Vital Statistics Reports; vol. 59 no 10. Hyattsville, MD: National Center for Health Statistics. 2011.

ii SJ Bandeali, WT Kayani, VV Lee, W Pan, MA Elayda, V Nambi, HM Jneid, M Alam, JM Wilson, Y Birnbaum, CM Ballantyne, SS Virani. "Outcomes of Preoperative Angiotensin-Converting Enzyme Inhibitor Therapy in Patients Undergoing Isolated Coronary Artery Bypass Grafting." Am J Cardiol, 2012 Jun 20. (Epub ahead of print.)

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