Beta-Blockers Reduce Long-term Mortality in High-Risk STEMI Patients

Yasuhiko Sakata, MD, PhD, of Osaka University Graduate School of Medicine (Suita, Japan), and colleagues analyzed 5,628 consecutive patients enrolled in the Osaka Acute Coronary Insufficiency Study (OACIS). The patients were admitted to 25 hospitals within 24 hours of STEMI and treated with PCI from April 1998 to April 2011.

Overall, slightly more than half of the patients (n = 2,880) were prescribed oral beta-blockers at discharge, including:

• Carvedilol (n = 2,075)
• Metoprolol (n = 559)
• Bisoprolol (n = 135)
• Atenolol (n = 33)
• Other beta-blockers (n = 78)

Effect Only Seen in Those at High Risk

After a median follow-up of 1,430 days, there was no difference in the rate of all-cause and cardiac death between those treated with vs. without beta-blockers (table 1).

Table 1. Incidence of Death

Propensity matching confirmed these results. Multivariate analysis revealed that beta-blocker treatment was not associated with a reduced risk for mortality (HR 0.935; 95% CI 0.711-1.230; P = 0.534).

However, subgroup analyses among the propensity-matched population showed that beta-blockers reduced the mortality risk for higher-risk patients, defined as those having Global Registry of Acute Coronary Events (GRACE) risk scores ≥ 121 (HR 0.596; 95% CI 0.416-0.854; P = 0.005) or those administered diuretics (HR 0.602; 95% CI 0.398-0.910; P = 0.016) but not for lower risk patients.

Potential for Guideline Changes?

“These results indicate that in high-risk patients, the beneficial effects of [beta-blocker] therapy may outweigh the risks, even in the contemporary PCI era,” Dr. Sakata and colleagues write, adding that further randomized controlled studies are warranted. Nevertheless, “our findings may suggest reevaluation of the current guidelines, which generally recommend implementing [beta-blocker] therapy for all post-STEMI patients.”

The authors note that beta-blockers may not have decreased mortality risk in the overall post-STEMI population due to the substantial decrease in mortality already associated with contemporary treatment strategies.

“It is likely that the recent decrease in long-term mortality may have masked the beneficial effects of [beta-blocker] therapy rather than indicating a change in the efficacy of [beta-blocker] therapy,” Dr. Sakata and colleagues acknowledge.

Harder Evidence Needed

In a telephone interview with TCTMD, Deepak L. Bhatt, MD, MPH, of Brigham and Women’s Hospital (Boston, MA), said the “results are probably true,” but pending a large, randomized clinical trial, changes to current guidelines are not warranted.

“I think their core finding is that in the primary PCI era the value of beta-blockers in STEMI is likely different from the thrombolytic era, which in turn is different from the pre-lytic era,” he said. “Primary PCI may have really changed the incremental value of routine beta blockade.”

With that said, Dr. Bhatt referenced the 2-part COMMIT trial (COMMIT [ClOpidogrel and Metoprolol in Myocardial Infarction Trial] collaborative group; Lancet. 2005;366:1607-1621), best known for showing a mortality benefit in STEMI patients with clopidogrel. “That study actually did not find a benefit of beta-blockers for the primary endpoint in STEMI patients. . . . I think sometimes doctors like to dismiss data that don’t fit their preconceived notions. That part of the study never really got as much attention as I think it deserved,” he argued.

The key to seeing a benefit from beta blockade is the presence of left ventricular dysfunction, Dr. Bhatt noted, adding that heart failure studies have shown a clear advantage compared with placebo. But “what is not so clear is the value of beta blockade in stable patients. [This study] raises the possibility that maybe everybody shouldn’t be on a beta–blocker, and maybe it should be used more judiciously than in current practice.”

Study Details

After 2009, approximately 80% of patients in the study received beta-blockers. Patients treated with beta-blockers were more often male, had higher BMIs, TIMI, and GRACE risk scores, and more often had hypertension, dyslipidemia, and cardiopulmonary arrest on arrival.

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