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Coronary Artery Disease

Coronary artery disease (CAD; also atherosclerotic heart disease) is the end result of the accumulation of atheromatous plaques within the walls of the coronary arteries that supply the myocardium (the muscle of the heart) with oxygen and nutrients. It is sometimes also called coronary heart disease (CHD). Although CAD is the most common cause of CHD, it is not the only one.

CAD is the leading cause of death worldwide. While the symptoms and signs of coronary artery disease are noted in the advanced state of disease, most individuals with coronary artery disease show no evidence of disease for decades as the disease progresses before the first onset of symptoms, often a "sudden" heart attack, finally arises. After decades of progression, some of these atheromatous plaques may rupture and (along with the activation of the blood clotting system) start limiting blood flow to the heart muscle. The disease is the most common cause of sudden death, and is also the most common reason for death of men and women over 20 years of age. According to present trends in the United States, half of healthy 40-year-old males will develop CAD in the future, and one in three healthy 40-year-old women. According to the Guinness Book of Records, Northern Ireland is the country with the most occurrences of CAD. By contrast, the Maasai of Africa have almost no heart disease.

As the degree of coronary artery disease progresses, there may be near-complete obstruction of the lumen of the coronary artery, severely restricting the flow of oxygen-carrying blood to the myocardium. Individuals with this degree of coronary artery disease typically have suffered from one or more myocardial infarctions (heart attacks), and may have signs and symptoms of chronic coronary ischemia, including symptoms of angina at rest and flash pulmonary edema.

A distinction should be made between myocardial ischemia and myocardial infarction. Ischemia means that the amount of blood supplied to the tissue is inadequate to supply the needs of the tissue. When the myocardium becomes ischemic, it does not function optimally. When large areas of the myocardium becomes ischemic, there can be impairment in the relaxation and contraction of the myocardium. If the blood flow to the tissue is improved, myocardial ischemia can be reversed. Infarction means that the tissue has undergone irreversible death due to lack of sufficient oxygen-rich blood.

An individual may develop a rupture of an atheromatous plaque at any stage of the spectrum of coronary artery disease. The acute rupture of a plaque may lead to an acute myocardial infarction (heart attack).

Top Coronary Artery Disease News Of 2023

***SPOILER ALERT: The following includes some solutions to our 2023 Cardiology Crossword Challenge***

Like years past, 2023 saw no shortage of studies aimed at reducing the burden of coronary artery disease, including research that focused on PCI, surgery, statins, and SGLT2 inhibitors in patients with acute MI.   

Few trials were more anticipated than the placebo-controlled ORBITA-2 trial, a study that confirmed a role for PCI in patients with stable angina (ORBITA; 39 Down). Unlike the first ORBITA study, which suggested PCI was no better than placebo when it came to improving exercise capacity at 6 weeks, ORBITA-2 showed that PCI significantly reduced the anginal symptom score, mostly through a reduction in the number of daily angina episodes, when compared with patients undergoing a placebo procedure.

Sanjit Jolly, MD (McMaster University/Population Health Research Institute, Hamilton, Canada), said that ORBITA-2 is an "important proof of concept" study showing that PCI does improve patient symptoms, something clinicians knew intrinsically. That said, he added, ORBITA-2 is unlikely to change how physicians currently practice.

For Jolly, one of the most important clinical trials presented this year was SELECT (34 Down) with semaglutide (Wegovy/Ozempic; Novo Nordisk). That study, presented at the American Heart Association (AHA) meeting in Philadelphia, PA, showed that the glucagon-like peptide-1 receptor agonist (GLP; 29 Down) reduced cardiovascular events—a composite of CV mortality, nonfatal MI, or nonfatal stroke—in overweight or obese patients with preexisting CVD who are not diabetic.    

"The Ozempic effect is clearly supported by the evidence," Jolly told TCTMD. "This is not just a weight-loss drug. This is cardiovascular risk reduction plus weight loss. It's really, really fascinating, and causing ripples in the stock market, affecting everything from airline stocks to joint replacements. The major challenge is now the availability of Ozempic in different geographies because there are shortages."

The year also brought some resolution to the debate around revascularization for left main coronary artery disease, an area of controversy since the 5-year EXCEL results led European surgeons to pull their support for the myocardial revascularization guidelines. A task force from the European Society of Cardiology and European Association for Cardio-Thoracic Surgery (ESC/EACTS) recommended that PCI (37 Across) for the treatment of left main CAD in patients at low surgical risk no longer carry a class I recommendation. Instead, PCI should be downgraded to a class IIa recommendation in those with a low-to-intermediate SYTAX score, according to the ESC/EACTS task force.   

Earlier this year, investigators announced the launch of ROMA-Women—a first-of-its-kind "sibling" study to the ongoing ROMA (12 Down) trial looking at multiarterial CABG grafting. Later, at the EACTS annual meeting in Vienna, Austria, an all-female panel of cardiac surgeons reminded their colleagues that women fare much worse than men after CABG surgery and emphasized the pressing need to study ways of closing this gap.

Earlier this summer, the American College of Cardiology (ACC) and AHA, along with several other professional bodies, released new guidelines for the management of patients with chronic coronary disease (CHRONIC; 61 Across). The new document provides ample recommendations for treatment, including directions on the use of SGLT2 inhibitors and GLP-1 receptor agonists in select patients, lipid-lowering therapy, antiplatelet therapy, and hypertensive medications, among other recommendations. 

When it comes to the benefits of lowering LDL cholesterol, the large, randomized, controlled REPRIEVE (1 Down) trial showed that these benefits also extend to patients with HIV treated with antiretroviral therapy. That National Institutes of Health-funded study, published in the New England Journal of Medicine, showed that pitavastatin cut the risk of major adverse cardiovascular events by 35% in this high-risk but often undertreated population.

Amid the ongoing push to understand the best timing and "completeness" of revascularization, the BIOVASC (42 Across) trial, presented at the ACC 2023 meeting in New Orleans, LA, gave operators some direction in ACS patients. Published simultaneously in the Lancet, the paper showed that an immediate procedure was just as safe as a staged procedures performed over the next few days or weeks.

Also under the revascularization umbrella, Jolly cited two important imaging trials to help inform clinical practice: ILLUMIEN IV and RENOVATE-COMPLEX-PCI. In the former, PCI guided by optical coherence tomography (OCT) was compared with angiography alone in high-risk patients with high-risk lesions. While stent placement was better with OCT, and there was a lower risk of stent thrombosis, its use did not lower the risk of target lesion failure at 2 years. Better results were seen in RENOVATE-COMPLEX-PCI, which included patients with true bifurcations, chronic total occlusions, and unprotected left main coronary artery disease. In this study, use of IVUS or OCT did lower the risk of target vessel failure at 2 years compared with angiography alone.

As of December 2023, said Jolly, the messaging around intravascular imaging usage is much more nuanced as a result of the two trials. "In anatomically complex patients, imaging is beneficial, but in fairly straightforward lesions you probably don't need it," Jolly summarized. "That's fairly valuable because there were really two camps—those who didn't believe in imaging and the others who believed in it like a religion where they considered it unethical not to do a case without it. Really, the evidence would suggest it's somewhere in the middle in terms of case selection and complexity, which I think makes sense clinically."

Like years past, 2023 also brought several studies looking to find the "sweet spot" (SWEET; 35 Across) when it came to the ideal duration for dual antiplatelet therapy (DAPT). In February, a meta-analysis showed that dropping aspirin after 1-3 months of DAPT was associated with no increase in fatal and ischemic events, but was linked to less bleeding, when compared with continuing standard DAPT. Less is more also appeared to be beneficial in patients with ACS undergoing PCI, although the updated European guidelines only support a short course of DAPT in ACS patients at high bleeding risk.

DAPA-MI (DAPAMI; 47 Across) was another anticipated trial of 2023, but the results were a bit mixed, with the study considered a "soft win" for dapagliflozin (Farxiga; AstraZeneca) when given to acute MI patients with either impaired LV function or Q-wave MI. Cardiometabolic outcomes were improved with treatment, but dapagliflozin did not reduce the risk of cardiovascular death/heart failure hospitalizations, which was the trial's original primary endpoint.

Investigators also took aim at the optimal transfusion strategy in MINT (59 Across), focused on acute MI patients with anemia. For the primary endpoint, there was only a trend toward reduced MI or mortality at 30 days with the liberal approach, where transfusions were given as needed to maintain hemoglobin 10 mg/dL until discharge, compared with a more restrictive strategy, although this and other endpoints moved in the right direction. Investigators led by Jeffrey Carson, MD (Rutgers Biomedical Health Sciences, New Brunswick, NJ), concluded that, at the very least, there was no harm associated with the liberal strategy.

Finally, Jolly cited the possible emergence of an oral PCSK9 inhibitor as one of the year's big stories. It's still early days for the investigational agent, MK-0616, but the introduction of an oral PCSK9 inhibitor that could lower LDL cholesterol would be a big deal—something that could one day be used safely alongside statins to reduce the global burden of cardiovascular disease.

Dear Doctor: Why Aren't Angioplasties, Stents Used More Often In Patients With Coronary Artery Disease?

DEAR DR. ROACH: I am 68 and in good shape; I work out daily. I had a few episodes of angina two to three years ago and started going to a cardiologist as a result. I have had quite a few tests done, but the one that was really concerning was my coronary artery calcium score, which is over 4,800 (not a misprint).

He put me on 80 mg of atorvastatin, 10 mg of ezetimibe and 40 mg of valsartan. My blood pressure is good (generally around 110 over 65 mm Hg), and other than some shortness of breath, I feel fine. I'm wondering if my doctor should be more aggressive due to the extremely high CAC score (i.E., a stent). I would really like to hear your thoughts about this. -- C.B.

ANSWER: Your extremely high calcium score means you are at a very high risk for, and probably have, blockages in the arteries that provide blood to the heart muscle. This condition is called coronary artery disease (CAD).

There are several medications that have been proven to reduce the risk of heart attack and death in people with coronary artery disease: statins (80 mg of atorvastatin is the highest dose of one of the most effective statins); ezetimibe (which works along with the statin to stabilize blockages); and ACE inhibitors and angiotensin blockers (valsartan probably has benefits beyond lowering blood pressure to prevent heart disease), all of which you are on. If your doctor was sure that you really have CAD, you should probably be on aspirin and a beta blocker as well, unless there is an underlying reason not to be.

Although stents are commonly placed after cholesterol plaque blockages are opened through a balloon procedure, they have not been proven, despite many studies, to reduce the risk of heart attack and death in people who have stable coronary artery disease. (The story is different for people who experience an emergency like a heart attack.)

Angioplasties and stents are normally reserved for people who have symptoms of heart blockages that have not been treated successfully with medications. A recent and still controversial study cast doubt on how effective stents are at relieving symptoms.

I can't tell if your shortness of breath is a symptom due to blockages of the heart. A cardiologist's clinical judgment is necessary to determine whether a test, such as an angiogram, is appropriate to see how many blockages there are and their severity. Although a CT scan with dye can give excellent information, an angioplasty and stent placement can only be done during a cardiac angiogram.

In a few cases, the blockages are so severe that a decision is made to go directly into surgery, where one or more grafts can be placed to bypass the blockages found on the angiogram. There are specific indications for cardiac surgery. Medications are much more effective than they used to be, so there are far fewer coronary artery bypass graft surgeries (CABG, always pronounced "cabbage") performed now than in decades prior.

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Dr. Roach regrets that he is unable to answer individual letters, but will incorporate them in the column whenever possible. Readers may email questions to ToYourGoodHealth@med.Cornell.Edu or send mail to 628 Virginia Dr., Orlando, FL 32803.

(c) 2022 North America Syndicate Inc.

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