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Beta-blockers for hypertension at noncardiac surgery can raise the risk major adverse cardiac events

Continued use of beta-blockers for hypertension during noncardiac surgery can raise the risk of major adverse cardiac events (MACE) and all-cause mortality within 30 days in a relatively low-risk population, suggests new research that is in line with earlier studies that generally included higher-risk patients.

A Danish cohort of more than 55,000 low-risk hypertension patients showed that those who were taking a beta-blocker plus another type of antihypertensive medication before noncardiac surgery had significantly increased 30-day postoperative risk of MACE and all-cause mortality compared with those who took non–beta-blocker antihypertensive drugs.

“The use of a large, real-world population for this study enhances the generalizability of these findings, and the consistency . . . with recent research enhances their plausibility,” write the investigators, led by Mads E Jørgensen (Gentofte Hospital, University of Copenhagen, Denmark).

Jørgensen said that the researchers also “did a number of subgroup analyses” that all pointed toward increased CV risks. “So for this type of patient, clinicians should keep these findings in mind.”

That said, he noted that this is an observational study. And although there was an associative risk with the beta-blocker treatment, “whether changing it out would translate into reduced risk and lower incidence of events we cannot say. We’d need randomized trials to answer that question.”

The findings were published online October 5, 2015 in JAMA Internal Medicine.

“A Hot Topic”

Thee European Society of Cardiology (ESC) and AHA/ACC released guidelines in 2014 downgrading from a class I recommendation to a class IIb for initiating beta-blockers in high-risk patients undergoing noncardiac surgery in the wake of controversy over the DECREASE series of trials.

Findings from the DECREASE group led to 2009 guidelines supporting the use of beta-blockers for this patient population. However, the series of trials has since been found to be “unreliable” and includes “fictitious data,” write authors of an analysis published in BMJ a month after the newer guidelines were released last year. In that analysis, the authors called for even stronger guideline revisions from the ESC, including a recommended reduction to class III (“not recommended”).

“After some trials were brought into question, it opened up the field to new research in this area. We went from a state where we thought that beta-blockers were always protective in noncardiac surgery to not being so sure who should actually receive or continue to receive this treatment,” said Jørgensen.

“This is a really hot topic, and it’s important to look at the clinical situation right now.”

MACE and Mortality

The investigators note that Danish guidelines were changed in 2009 “to remove beta-blockers from the first-line therapies for hypertension, but [they] are still used in antihypertensive polypharmacy.” Therefore, they wanted to assess patients who used at least two antihypertensives as long-term treatment.

In the analysis, they evaluated Danish health records for 55,320 hypertension patients without cardiac, renal, and liver disease who underwent noncardiac surgery between 2005 and 2011. A beta-blocker was part of the two-drug regime for 14,644 of these patients. Other antihypertensives used by the participants included renin-angiotensin system (RAS) inhibitors, thiazides, and calcium antagonists.

The primary outcomes were 30-day all-cause mortality and incidence of MACE, which was defined as a combination of CV death, nonfatal ischemic stroke, and nonfatal MI.

In the patients who included a beta-blocker in their treatment, 1.32% had MACE 30-day postsurgery vs 0.84% of the non–beta-blocker group (P <0.001). When researchers examined the MACE components individually, CV death was also significantly higher in the beta-blocker–treated group (0.90% vs 0.45%, respectively, P<0.001.)

All-cause mortality was 1.93% vs 1.32% in the beta-blocker vs non–beta-blocker groups, respectively (P<0.001).

In addition, all treatment combinations that included a beta-blocker had significantly increased risk of both MACE and all-cause mortality compared with the reference treatment of RASIs and thiazides.

Odds Ratio (OR) for 30-Day MACE* for Two-Drug Regimens

Group OR (95% CI)
Beta-blocker + RAS inhibitors 2.16 (1.54–3.04)
Beta-blocker + thiazide 1.56 (1.10–2.22)
Beta-blocker + calcium antagonists 2.17 (1.48–3.17)
*Compared with renin-angiotensin system (RAS) inhibitors plus thiazides

OR for All-Cause Mortality* for Two-Drug Regimens

Group OR (95% CI)
Beta-blocker + RASIs 1.79 (1.33–2.42)
Beta-blocker + thiazide 1.65 (1.24–2.18)
Beta-blocker + calcium antagonists 1.68 (1.20–2.35)
*Compared with RAS inhibitors plus thiazides

“Patients treated with any combination of other antihypertensive drugs only were not at increased risk of MACE or mortality, compared with the reference,” report the investigators.

The greatest associations between beta-blocker use and increased risk of MACE were for the men (number needed to harm [NNH] 140), those who were 70 years of age or older (NNH 142), and for those undergoing acute rather than elective surgery (NNH 97).

The findings “may suggest that perioperative management of patients with hypertension should receive specific attention in clinical practice and future guidelines, but additional randomized clinical trials on this question may be warranted,” write the researchers.

Still, Jørgensen noted that “it’s important to assess the individual patient and the interdisciplinary team taking care of the patient prior to surgery and to keep these findings as one of many important factors to consider when doing the preoperative evaluation.”

Reference:

  1. Jørgensen ME, Hlatky MA, Køber L, et al. B-blocker-associated risks in patients with uncomplicated hypertension undergoing noncardiac surgery. JAMA Intern Med 2015; DOI:10.1001/jamainternmed.2015.5346. Abstract

 

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