Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echo Study - IV - DECREASE-IV

Description:

The goal of the trial was to evaluate treatment with beta-blockers and statins among intermediate-risk patients undergoing noncardiovascular surgery.

Hypothesis:

Beta-blockers and statins will independently reduce the risk of perioperative cardiovascular events.

Study Design

  • Randomized
  • Placebo Controlled
  • Factorial

Patient Populations:

  • Patients at least 40 years of age undergoing elective noncardiovascular surgery


    Number of screened applicants: 45,000
    Number of enrollees: 1,066
    Duration of follow-up: 30 days
    Mean patient age: 65 years
    Percentage female: 40%

Exclusions:

  • Use of or contraindication to study medication
  • Emergency surgery
  • Inability to provide informed consent
  • Previous participation in another DECREASE trial

Primary Endpoints:

  • Cardiovascular death or nonfatal myocardial infarction within 30 days

Secondary Endpoints:

  • All-cause mortality
  • Cardiac arrhythmias
  • Acute heart failure
  • Coronary revascularization
  • Stroke
  • Clinically significant bradycardia and hypotension
  • Clinically significant liver dysfunction
  • Creatine phosphokinase >10 times the upper limit of normal
  • Rhabdomyolysis

Drug/Procedures Used:

Intermediate-risk patients undergoing noncardiovascular surgery were randomized with a 2 x 2 factorial design to bisoprolol (n = 264), fluvastatin (n = 265), combination therapy (n = 269), or double control (n = 268).

Bisoprolol was started at a dose of 2.5 mg daily and titrated to a maximum of 10 mg daily to target heart rate of 50-70 bpm. The dose of fluvastatin was 80 mg daily.

Principal Findings:

Due to slow enrollment, the trial was terminated early after 1,066 patients were randomized. The mean age was 65 years, 40% were women, 10.8% had diabetes, 5.1% had a prior myocardial infarction, and 4.3% had a prior stroke. General surgery was used in 93.9% with the remainder performed by spinal or local anesthesia. The top five surgical procedures were: general surgery (38.9%), urology (19.3%), orthopedics (16.3%), ear-nose-throat (12.4%), and gynecology (5.0%). Study medication was started a median of 34 days prior to surgery.

The primary outcome of cardiovascular death or nonfatal myocardial infarction occurred in 2.1% of the bisoprolol group versus 6.0% of the bisoprolol-control group (p = 0.002). Cardiovascular death or nonfatal myocardial infarction occurred in 3.2% of the fluvastatin group versus 4.9% of the fluvastatin-control group (p = 0.17).

Interpretation:

Among patients at intermediate risk undergoing noncardiovascular surgery, the preoperative use of bisoprolol for a median of 34 days was beneficial. This therapy reduced the composite outcome of cardiovascular death or nonfatal myocardial infarction. The POISE trial documented a lower frequency of myocardial infarction with beta-blockade; however, this occurred at a cost of increased stroke and overall mortality. The DECREASE-IV trial required initiation of study medication approximately 1 month before surgery with dose titration to a target heart rate, while the POISE trial initiated a large dose of study medication without dose titration immediately before surgery.

Although this trial did not reveal benefit of preoperative statin therapy, meta-analyses have documented a reduction in myocardial infarction, especially after percutaneous coronary intervention from this strategy (see Winchester DE, et al. J Am Coll Cardiol 2010;28:1099-1109, and Patti G, et al. Circulation 2011;123:1622-32). While statin therapy does not require dose titration, the optimum dose and duration of this medication prior to surgery is unknown.

References:

Dunkelgrun M, Boersma E, Schouten O, et al. Bisoprolol and fluvastatin for the reduction of perioperative cardiac mortality and myocardial infarction in intermediate-risk patients undergoing noncardiovascular surgery: a randomized controlled trial (DECREASE-IV). Ann Surg 2009;249:921-6.

Clinical Topics: Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Lipid Metabolism, Nonstatins, Novel Agents, Statins

Keywords: Myocardial Infarction, Stroke, Follow-Up Studies, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Fatty Acids, Monounsaturated, Orthopedics, Heart Rate, Percutaneous Coronary Intervention, Nose, Gynecology, Indoles, Urology, Pharynx, Bisoprolol, Diabetes Mellitus


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