Beta-Blockers Not Beneficial After PCI for Stable Angina

Older patients with stable angina who undergo elective PCI do not appear to benefit from taking beta-blockers after their procedure, according to a new study.

In a large analysis of more than 700,000 patients in the National Cardiovascular Data Registry (NCDR) CathPCI Registry, researchers report that the use of beta-blockers in revascularized stable angina patients without a history of MI, systolic heart failure, or impaired left ventricular function did not result in a reduction cardiovascular events in short- and long-term follow-up.

“I have started seeing my patients differently, started seeing beta-blocker therapy in these patients differently,” said study author Valay Parikh, MD (Staten Island University Hospital, NY). “I no longer just blindly give beta-blockers to everybody. I consider whether another therapy might be beneficial, rather than simply giving beta-blockers as a first choice.”

In an editorial accompanying the study, Anthony Nappi, MD (Albany Medical College, NY) and William Boden, MD (Veterans Affairs New England Healthcare System, Boston, MA), state that this study and others have raised important questions about the continued use of beta-blockers in CAD patients undergoing PCI. While beta-blockers are a class I recommendation for up to 3 years after an acute MI, the evidence supporting their use has been extrapolated to all patients with CAD, and in many instances, without strong data to back it up.

Speaking with TCTMD, Sripal Bangalore, MD (NYU Langone Medical Center, New York, NY), who was not involved in this analysis but who has conducted similar studies on the use of beta-blockers, said that in stable patients without heart failure, the majority are still being treated with beta-blockade. In previous studies, he and others have “shown there is absolutely no evidence that beta-blockers in these patients actually has a prognostic benefit in terms of reducing death or MI,” said Bangalore. “We just don’t have the data from randomized trials.”   

Results of the study, which were published online yesterday ahead of print in JACC: Cardiovascular Interventions, suggest that the use beta-blockers in this specific patient population, should be “individualized” or considered on “case-by-case basis,” according to the study authors and editorialists.

Evidence Supporting Use Is Weak

Speaking with TCTMD, Parikh said beta-blockers have consistently been shown to reduce cardiovascular outcomes, including mortality, in CAD patients with MI and systolic heart failure. Based on the strength of the evidence, use of beta-blockers is a class I recommendation from the American College of Cardiology/American Heart Association in these patients. The drugs are also an important component of optimal medical therapy for patients with stable angina not undergoing coronary revascularization.

“We chose a very specific subset of the population where the evidence is not that strong but still where beta-blocker use is recommended by different groups,” said Parikh. “We looked at patients with stable angina who didn’t have a history of MI or systolic heart failure and who underwent PCI. It’s a very particular subset—the evidence for beta-blocker use is a IIa indication and the level of evidence is weak (C). There is not much available evidence on this topic.”

The study included 755,215 patients undergoing PCI between 2005 and 2013, of whom 71.4% were discharged with a beta-blocker prescription. At 30 days and 3 years, there were no differences in the adjusted mortality, MI, stroke, or coronary revascularization rates among individuals prescribed beta-blockers compared with those not treated with the drugs. There was an increase in the risk of rehospitalization related to heart failure for those treated with beta-blockers at 30 days (adjusted HR 1.70; 95% CI 1.43-2.02) as well as 3 years (adjusted HR 1.18; 95% CI 1.12-1.25).

“You can look at this two ways,” said Parikh. “One, you can say the beta-blockers were really not helpful at all, or two, you could argue that the patients who received beta-blockers were sicker to begin with and beta-blockers provided them some beneficial effect, but not enough to show a difference against the other group. It’s really hard to say, but the bottom line is that if a patient has angina and other indications, such as systolic heart failure or a previous MI, then definitely beta-blockers should be given. But in patients without any indications, physicians should really consider whether or not beta-blockers should be prescribed.”

In their editorial, Nappi and Boden make a similar point, noting that those prescribed beta-blocker therapy had a higher prevalence of cardiovascular risk factors. As a result, it is possible these patients were prescribed beta-blockers after PCI because they had more complex anatomic coronary disease or an incomplete revascularization.

“In those cases, the treating physician also may have been concerned about ongoing ischemia,” write Nappi and Boden. “Considering these possibilities, one may interpret these data from the perspective that the use of beta-blocker therapy was effective therapeutically, because the patients in that group did not have a higher incidence of ischemic events.”

For Bangalore, the evidence supporting the use of beta blockers is most robust in post-MI patients, but even then the data are not particularly relevant to today’s practice. “In the post-MI setting, the majority of the trials were performed before the reperfusion era, before the modern era of medical therapy,” he said. “In a way, you’re using data from the post-MI patients and extrapolating, but you’re also using really older trials which were positive.”

In one recent analysis of the REACH registry, Bangalore and colleagues showed there was no reduction in cardiovascular outcomes among stable patients with CAD risk factors, those with prior MI, or those with CAD but without a prior MI who received beta-blockers. In another study, which was an analysis of beta-blocker use in the contemporary treatment of MI, the drugs were associated with a reduction in MI and angina, but not mortality. “There was some benefit, but also some harm,” he told TCTMD, noting beta-blockers were associated with an increase in heart failure, shock, and drug discontinuation in that analysis.

Heart Failure Finding Might Be Spurious

To TCTMD, Parikh said the reason for the increased risk of heart failure with beta-blocker therapy is not known, and he cautioned against overinterpretation. He stressed the observational nature of the study, noting the heart failure result could be a spurious finding.

Over the study period, the researchers observed a gradual increase in the use of beta-blockers. In clinical practice, Parikh said beta-blockers are routinely prescribed in CAD patients without a prior MI or systolic heart failure.

“It’s commonly believed that all coronary artery disease patients should be on beta-blockers unless they have a contraindication or are unable to tolerate the drugs,” he said. “If they can tolerate the drugs, the ‘common sense’ cardiology practice to date has been to put every patient on them. I can’t blame physicians because all the guidelines recommend giving beta-blockers.”

As for Nappi and Boden, they are not particularly surprised about the increase in beta-blocker prescriptions over time, noting that the registry data analyzed spans 2005 to 2013, a time when trials such as COURAGE, BARI-2D, FAME, and FAME 2 were published. Those studies highlighted the advantages of medical therapy for stable ischemic heart disease and the performance of PCI for flow-limiting lesions assessed by fractional flow reserve.

Parikh noted it’s unlikely a randomized trial testing beta-blockade in stable asymptomatic CAD patients will ever be conducted, mainly because the trial would be enormous and the drugs are currently generic. Boden and Nappi agree, noting this leaves physicians in a bit of a bind. 

“Thus, absent new data to guide current therapy, clinicians will need to decide whether they will continue to extrapolate older scientific evidence of beta-blocker efficacy in selected post-MI populations from an earlier era before the advent of PCI and optimal medical therapy to the current era of contemporary clinical practice, where perhaps such treatment decisions need to be guided more by physician judgment, and hence individualized to the level of patient benefit versus risk, because such definitive evidence is either imperfect or lacking,” they write.

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