Published in the July 2007 issue of Today’s Hospitalist.
It’s a frightening reality, according to cardiologist Prediman K. Shah, MD: In close to 50% of all cases, the first time patients learn that they have coronary artery disease is when they suffer an acute coronary syndrome (ACS). That’s why, Dr. Shah explained, treatment of the acute condition must be closely tied to management of the patient’s underlying atherosclerosis.
At ACP’s annual meeting this spring, Dr. Shah, who is professor of medicine at UCLA as well as chair of cardiology and director of the Atherosclerosis Research Center at Cedars-Sinai Medical Center in Los Angeles, acknowledged that the immediate goal is to stabilize the patient. But he also said that physicians need to "focus on the donut, and not just on the hole."
While removing blockages is key to fixing problems in "the hole," he said, treating "the donut" will address the underlying atherosclerosis. That strategy, he said, is key to preventing other lesions from rupturing.
High-risk patients with unstable angina
To guide treatment of patients with unstable angina, Dr. Shah said that it is helpful to be able to predict which patients are at the highest risk for something going seriously wrong. He recommended using the seven-point TIMI risk score for unstable angina. (See "TIMI risk score for unstable angina," right.)
The most worrisome patients, Dr. Shah explained, are those who exhibit an EKG abnormality, including ST and T wave abnormalities; those with elevated enzyme levels; and those with persistent C-reactive protein elevation, a sign of persistent inflammation. Older patients are "much worse off than younger patients," as are diabetic patients. Hemodynamic compromise “evidence of hypotension or associated heart failure “also puts patients in a very high-risk category.
Other high-risk patients are those with unstable angina after an MI, angina patients who have failed aspirin therapy, and those with multi-vessel or left main coronary disease as seen angiographically.
Acute medical management
In terms of medical management, anti-thrombotics are the first line of defense.
Anti-ischemics are the other class of drugs commonly used to treat unstable angina. But according to Dr. Shah, they generally provide only symptomatic relief and do not reduce the risk of MI or death. That is particularly true of nitrates and calcium channel blockers, he said, although beta-blockers do have some "modest favorable effect."
With anti-thrombotics, the most important therapy, low-dose aspirin should be your "cornerstone" intervention, Dr. Shah said. (The exception is patients who receive a stent. For them, he recommended full-dose aspirin for about six months.)
Adding clopidogrel to aspirin does increase the benefit, but only modestly, he pointed out. Because adding clopidogrel to aspirin substantially increases costs without adding much benefit, he urged physicians to hold off on giving patients clopidogrel on admission, except for very high-risk patients. Instead, he recommended waiting to order the drug until after angiography, to make sure you can rule out the need for bypass surgery.
On the other hand, adding heparin to aspirin in the acute phase of unstable angina appears to work better than using either drug alone. Another advantage of using the combination therapy is that when heparin is eventually withdrawn, the patient is already benefiting from aspirin and has less risk of ischemic rebound.
"You have fewer recurrences or reactivation after withdrawal of heparin if you had aspirin on board than if you used only heparin and withdrew it after 48 hours," Dr. Shah explained. Moreover, he said, the main advantage to using low molecular weight heparin over unfractionated heparin is convenience. Studies, he said, have found neither an overwhelming efficacy nor a safety advantage.
"IIb or not IIb"
Studies have also found no reason to routinely use the newer GP IIb-IIIa receptor agonist antiplatelet medications, including abciximab, tirofiban and eptifibatide, when managing unstable angina.
These agents, which are relatively expensive and can increase bleeding risks, are best used periprocedurally, in combination with a percutaneous coronary intervention (PCI).
"In the cath lab, physicians have the opportunity to use an infusion acutely and for up to 12 hours when they see a lot of thrombotic burden in the culprit vessel," he said. Another indication for a GP IIb-IIIa receptor agonist, he pointed out, is when physicians put in a stent and see a residual thrombus creating sluggish flow.
There is seldom a need to start IIb-IIIa therapy before a cath procedure, he added, because it offers no major benefit compared to aspirin and heparin.
Routine or selective catheterization?
Once a patient is stabilized and no longer in acute distress, the question for physicians is whether the patient needs to go to the cath lab right away “or at all “for cardiac catheterization.
Patients with acute coronary syndrome are highly likely to have a major lesion that is as much as 80% obstructed in at least one coronary vessel. About two-thirds of these patients will have multi-vessel disease, while 5% will have a particularly dangerous left mainstem obstruction.
Should all these patients receive immediate catheterization? Or can you wait and recommend angiography, then move to catheterization only if patients have recurrent ischemia or a markedly abnormal stress test after being stabilized?
Over the years, Dr. Shah said, the evidence has swung both ways. The latest studies show that waiting and using an invasive strategy selectively results in "no difference in mortality or recurrent myocardial infarction" compared to a routine approach where everyone goes to the cath lab right away.
"If anything, the only advantage for early invasive treatment was fewer recurrent hospitalizations for recurrent ischemia," Dr. Shah said. He cited one study that could not demonstrate the superiority of an early invasive strategy over a selective one in patients without ST-segment elevation and with an elevated cardiac troponinT level who were given optimized medical therapy.
On the other hand, he pointed out, the study, which was published in the Sept. 15, 2005, New England Journal of Medicine, also found that most patients “70% of those selectively managed “end up being catheterized within a year anyway.
"You can get away with delaying catheterization," said Dr. Shah, "but a large proportion of patients will land in the cath lab because the recurrence rate of ischemia is quite high in conservatively managed patients."
When every second counts
One instance where you don’t wait is for patients who are suffering an ST elevation myocardial infarction. For these patients, he stressed, "every minute that goes by, more and more muscle is irreversibly dying." Without catheterization, these patients can suffer almost complete damage to the ischemic zone in as few as four hours. "The key is timely perfusion."
The best way to accomplish perfusion, said Dr. Shah, is PCI or angioplasty. More than 20 trials have confirmed that PCI works better than lytic therapy for treating an ST elevation MI in terms of just about every marker, from mortality, shock and recurrent infarction to stroke and intracranial hemorrhage.
The same studies have also shown that it is better to transfer a patient to a PCI facility than to give that patient lytic therapy. For these patients, he said, "PCI wins over lytic therapy, even when there is a delay in transferring the patient to a PCI facility."
A hybrid approach, in which lytic therapy is initiated while the patient is en route to a PCI facility, may be a reasonable compromise for some patients.
Long-term management: stents and more
After acute treatment, the next step is long-term management. ACS patients need both immediate follow-up based on the care they received during their acute phase and preventive care to stave off recurrence.
In terms of immediate follow-up care, understanding the implications of long-term antiplatelet therapy for all patients is key. That applies whether patients received a stent along with their angioplasty or they had conventional balloon angioplasty. Patients receiving only balloon angioplasty need "aspirin forever,"
Dr. Shah said, while high-risk patients should take clopidogrel for four to six weeks.
Because the risk of a lethal stent thrombosis is so high in the first six weeks with a bare-metal stent, Dr. Shah said that hospitalists must stress to patients that they need to take clopidogrel everyday for that period of time. (They likewise will need to take aspirin for the rest of their lives.)
Plavix, he pointed out, "is so unforgiving that skipping it for one or two doses can land the patient with a 10-fold higher risk of stent thrombosis."
The big problem with drug-eluting stents, on the other hand, has more to do with long-term elevated risks of thrombosis, even up to a year or two or more after implantation. The "monster problem" created by drug-eluting stents is that patients need combination antiplatelet therapy "for a year and possibly indefinitely if there are not specific contraindications," Dr. Shah said. While this may not be the recommendation on the package insert, he said it is "our experience."
With growing awareness of the increased risk of late stent thrombosis, Dr. Shah said he was gratified to see the proportion of patients getting bare-metal stents going up and the popularity of drug-eluting stents going down. (Drug-eluting stents are best used, he noted, for smaller, discreet lesions where the risk of stent thrombosis is less and the benefit of restenosis is great.) "Restenosis is almost never lethal," he explained, "but a thrombosis is a potentially lethal complication."
For a patient with a six-month-old drug-eluting stent and atrial fibrillation who now has a GI bleed, Dr. Shah said that he tells physicians to stop only the patient’s aspirin, not clopidogrel. Stent thrombosis invariably will lead to a massive myocardial infarction and a risk of death as high as 40%, he said. "You have to accept the risk of bleeding rather than the risk of thrombosis," he said.
Treating underlying disease
While opening an artery can be an immediate lifesaver, it’s only a stopgap measure, Dr. Shah stressed, because the real disease remains.
As many as one in five ACS patients risk having a recurrent ischemic event within a year, either in the same artery or a neighboring one, due to diffuse coronary artery disease. That means that physicians’ key responsibility after an acute event is to do whatever possible to prevent the predictable.
To prevent more lesions from rupturing, physicians’ goals should be to reduce lipids and plaque inflammation.
To do so, start ACS patients on statin therapy to lower LDL before they are discharged. Statins, said Dr. Shah, are a key way to address underlying disease because they reduce lipid content and plaque inflammation, stabilizing atherosclerotic lesions. As far as reducing the number of clinical events, using high doses rather than a lower-dose statin results in only a modest incremental benefit.
Coming down the pike, he said, there may be therapeutic agents that raise HDL levels to affect lipid content and inflammation. Studies are now looking at whether these drugs are safe.
One way to raise HDL right now, he added, is by using niacin. A drug currently in clinical trials combines niacin with a flush blocker that may make niacin more palatable to the many patients who can’t tolerate it.
Other therapies that help prevent future acute coronary events are ACE inhibitors, beta-blockers and lifestyle changes, particularly a routine low-fat or Mediterranean diet that is low in trans fats and rich in omega-3 fatty acids.
"The Mediterranean diet seems to work better than even statins to reduce recurrent events," Dr. Shah said. "Remind your patients that diet can be as powerful or more powerful than drugs."
Deborah Gesensway is a freelance writer who reports on U.S. health care from Toronto, Canada.
The role of angiography
According to cardiologist Prediman K. Shah, MD, from Cedars-Sinai Medical Center in Los Angeles, angiography plays an important role in managing patients with acute coronary syndrome (ACS). Physicians should rely on angiography before ordering clopidogrel, for instance.
"If a patient needs bypass surgery acutely," said Dr. Shah, who gave an update on ACS at the American College of Physicians’ annual meeting earlier this year, "it becomes a real hassle to have clopidogrel on board."
Angiography can also help with diagnosis, particularly for rare conditions that can cause ACS symptoms. Several uncommon conditions that mimic acute coronary syndrome with chest pain and enzyme abnormalities, as well as ST and T wave abnormalities, include acute viral myopericarditis, spontaneous coronary artery dissection, acute vasculitis, Takotsubo syndrome, and endocarditis with coronary embolism.
"Sometimes you have zebras," Dr. Shah explained. "Be aware that zebras can look like horses until you do an angiogram."
A polypill strategy to reduce cardiovascular disease
“¢ Aspirin (75 mg)
“¢ Beta-blocker, diuretic, ACE inhibitor
“¢ Cholesterol lowering agent (statin, 40 mg)
“¢ Folic acid (0.8 mg)
Source: British Medical Journal