In Stable Heart Disease, Study Finds Stents Might Be No Better Than Drugs

Invasive procedures like stents are often no better than medical therapy and lifestyle changes at preventing a heart attack in patients with stable heart disease, according to a large, $100-million federal study that sought to resolve a debate over which approach is best.

Results from ISCHEMIA, funded by the National Heart, Lung, and Blood Institute, are likely to change practice guidelines, according to commenters who took part in Saturday’s packed presentation at the 2019 American Heart Association Scientific Sessions in Philadelphia, Pennsylvania.

The trial was designed to measure the time to a primary end point, which in this case was cardiovascular death, heart attack, or hospitalization for angina, heart failure, or resuscitated cardiac arrest.

Study cochair Judith Hochman, MD, senior associate dean of Clinical Sciences at NYU Langone Medical Center, presented data that showed that a conservative treatment approach with medication only offered slightly less likelihood of an event (1.9%) within the first 6 months, while an invasive procedure would have the slight edge (by 2.2%) after 4 years.

A substudy, called ISCHEMIA-CKD, found that for a group of patients who also had chronic kidney disease, invasive procedures did not reduce the risk of clinical outcomes. Commentator Glenn Levine, MD, a professor at Baylor College of Medicine, said the data in the trial will allow members of guidelines committees to develop treatment recommendations in this area. Right now, he said, “there simply aren’t any.”

The one caveat to the overall finding: for patients with frequent angina, invasive procedures can offer improvement in quality of life, and this should lead to shared decision-making, said John A. Spertus, MD, MPH, of Saint Luke’s Mid-America Heart Institute, who presented patient-reported outcomes from ISCHEMIA.

A Complex Question, a Complicated Trial

For more than a dozen years, cardiologists have debated the best way to deal with blockages in an artery. In an acute case, such as when a patient has a heart attack, using a catheter to place a stent can be life-saving. But because procedures themselves can be risky—and costly—and because of advances in therapy, there’s been debate whether some stents or bypass procedures could be avoided in favor of medication, along with changes to diet and exercise.

To answer this question, the investigators for ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) enrolled patients with moderate to severe ischemia—but who had not had a heart attack within the past 2 months—to receive either an invasive procedure, such as a stent or coronary bypass, or medical therapy.

Because of exclusion criteria to leave out with patients with the most serious conditions—including left ventricular ejection fraction <35% and low kidney function--the trial was slow to enroll patients. Thus, the original primary end point was expanded from cardiovascular death and non-fatal myocardial infarction (MI) to the current 5-part end point. This generated some controversy, but researchers said it did not affect the study’s outcome. The trial was also unblinded, so there were no “sham” procedures to act as controls.

In the end, ISCHEMIA enrolled 8518 patients and randomized 5179; 73% of these patients had blinded CT angiography to exclude life-threatening conditions, then 2588 received an invasive procedure, and 2591 received therapy. Median follow-up was 3.3 years; the full trial lasted 7 years.

Although the researchers expanded the end point, results for the original components were consistent:

• The adjusted hazard ratio (HR) for the primary outcome, invasive vs conservative, was 0.93 (0.80, 1.08), P = .34.
• The adjusted HR for the major secondary outcome—CV death or MI&mdash;was 0.90 (0.77, 1.06), P = .21.
• Similar results between the 2 arms were seen for net clinical benefit (3-year follow-up, includes stroke), and cardiovascular death.
• The probability of a least a 10% benefit from an invasive procedure on all-cause mortality was <10%, based on a pre-specified Bayesian analysis.

Change in Medical Practice

Both Levine, who commented on ISCHEMIA-CKD, and Alice K. Jacobs, MD, of Boston University School of Medicine, who commented on the main findings, said the results would give comfort to physicians who wanted to manage patients with therapy rather than immediately sending patient to the catherization lab.

Until this trial, Jacobs said, “The data are conflicting, and there is equipoise in the community, but I think there is a nagging undertow of concern about not withholding the invasive strategy in patients with moderate to severe ischemia, because of the fear of exposing them to adverse outcomes.”

Levine remarked, "I will generally not go searching for ischemia and CAD in most severe and end-stage CKD patients, absent marked or unacceptable angina, and will treat them with medical therapy alone.”