Managing Chronic Angina: What Do We Know?

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While there are a multitude of drugs and lifestyle changes that are prescribed for chronic angina, properly managing this patient population continues to challenge cardiologists. However, recent studies have begun to reveal new therapies that might better relieve this chronic pain.

Why COURAGE is so encouraging

Treatment strategies for chronic angina differ depending on the varying underlying causes—atherosclerosis, vascular disease or ischemia. Even between men and women, management of this condition is difficult and multifaceted. The landmark 2007 COURAGE trial, however, suggests that optimal medical therapy (OMT) plus PCI offers no benefit in terms of mortality or subsequent MI compared with OMT alone (New Engl J Med April 2007;356:1503-1316).

"The results of COURAGE indicate that some expensive stenting procedures could be avoided," says principal investigator William E. Boden, MD, clinical chief of cardiovascular medicine at University at Buffalo Schools of Medicine & Public Health in Buffalo, N.Y.

Women present with calcium differently than men, so it’s important to choose the most appropriate diagnostic test. A. Coronary artery calcium scan shows calcium, while coronary CT angiography images (B and C) show normal arteries. Source: Obstet Gynecol 2010;115:156-169

Likewise, the BARI 2D trial, also led by Boden, randomized type 2 diabetic patients and heart failure patients to receive PCI or CABG plus OMT or OMT alone. Patients had a diagnosis of coronary artery disease (CAD) and classic angina. Results showed no difference in terms of mortality between the revascularization approaches and OMT (N Engl J Med 2009;260:2503-2515).

However, both trials showed some relief from angina associated with PCI, suggesting a more personalized approach in treating patients with stable angina with PCI is warranted.

OMT should consist of the maximum tolerated doses of anti-anginal drugs, such as beta-blockers, nitrates and calcium-channel blockers, in addition to aggressive risk-factor modification, such as lipid control with statins, blood pressure control, weight management and smoking cessation, offers Prakash Deedwania, MD, chief of cardiology at the University of California, San Francisco, School of Medicine.

The COURAGE–inspired theory is that OMT prevents widespread atherosclerosis and, when aggressive, potentially stabilizes plaques. However, no anti-anginal drugs are disease modifying, meaning they do not change the risk of MI, sudden cardiac death or all-cause mortality.

The anti-anginal drug ranolazine (Ranexa, Gilead Sciences), approved by the FDA in 2006, could be beneficial to treat chronic angina, particularly in diabetic and heart failure patients, in addition to those with low heart rates and low blood pressure. "It is a needed addition to the armamentarium of clinical cardiologists who manage patients with angina," writes Richard Kones, MD, from the Cardiometabolic Research Institute in Houston (Vascul Health Risk Mangmnt 2010;6:749–774).

Kones notes that ranolazine was not used in the COURAGE trial, but based upon its use in the MERLIN-TIMI 36 trial, "it is likely that ranolazine not only has a place in OMT for stable angina, but also possibly for chest pain associated with ACS as well."

Being a relatively new drug, ranolazine is more expensive than generic beta-blockers and nitrates, but is cheaper than therapies such as enhanced external counterpulsation, and can be helpful in many patients refractory to traditional drugs, Deedwania says.

Battle of the sexes

Women have a higher prevalence of angina than do men; however, the lack of certainty as to why makes treatment difficult, says Kamakki Banks, MD, MPH, leader of the Dallas Heart Study and cardiology research fellow at the University of Texas Southwestern Medical Center in Dallas.

During the epidemiologic Dallas Heart Study, Banks and colleagues assessed 1,480 women to evaluate clinical characteristics of women with angina. The women were between the ages of 30 and 65, and 6.9 percent had angina without the presence of coronary artery calcium (CAC).

In those patients with CAC, the researchers found that angina was not associated with the presence or amount of calcium. However, many women did have increased levels of soluble intercellular adhesion molecule (sICAM-1), soluble vascular cell adhesion molecule (sVCAM-1) and lower aortic compliance, which suggest microvascular dysfunction. Banks says therapies that focus on treating endothelial