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


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


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%


  • 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).


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.


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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