DIAMOND-CHF

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Torp-Pedersen C, et al. "Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group". New England Journal of Medicine. 1999. 341(12):857-865.
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Clinical Question

In patients with congestive heart failure with reduced left ventricular function, does Dofetilide affect mortality or morbidity?

Bottom Line

In patients with HFrEF, Dofetilide was effective in cardioverting atrial fibrillation, decreasing its recurrence, as well as decreasing hospitalization for worsening heart failure without increasing mortality when compared to placebo.

Major Points

Guidelines

Design

Population

Inclusion Criteria

  • Hospitalization for new or worsening CHF
  • PND and/or SOB with rest or exertion within 30 days of randomization
  • At least 18 years of age
  • postmenopausal or on oral contraception
  • Wall motion index less than or equal to 1.2
  • EF less than or equal to 35%.
  • Provided signed consent

Exclusion Criteria

  • MI within 7 days of randomization
  • Heart rate less than 50 beats per minute during awake hours
  • Sinoatrial block
  • 2nd degree or 3rd degree av block not treated with pacemaker
  • CrCl less than 20 cc per minute
  • Any history of drug induced arrythmia
  • QTc greater than 460 or greater than 500 if LBBB
  • Diastolic BP greater than 115 mmhg
  • Systolic BP less than 80 mmhg
  • Potassium less than 3.6 m Mol per liter or higher than 5.5 m Mol per liter
  • Cardiothoracic surgery in the preceding 4 weeks
  • Aortic stenosis
  • Any planned cardiac surgery or planned angioplasty
  • Myocarditis
  • Any Significant liver dysfunction
  • Recent Class I or Class III arrhythmia drug use
  • History of AICD placement

Baseline Characteristics

  • DOFETILIDE (N=762) vs PLACEBO (N=756)
  • Median duration of heart failure (months) 12 vs 12
  • Age Mean (Yrs): 70 vs 70
  • Age Range (Yrs) 26–94 vs 32–92
  • Male sex no: (%) 546 (72) vs 568 (75)
  • Current smoker no: (%) 254 (33) vs 268 (35)

Medical history no. (%)

  • Myocardial infarction 389 (51) vs 509 (67)
  • Ischemic heart disease 152 (20) vs 111 (15)
  • Diabetes 390 (52) vs 508 (67)
  • Hypertension 140 (19) vs 115 (15)
  • Creatinine clearance ml/min 57±23 vs 57±25
  • Atrial fibrillation no. (%) 190 (25) vs 201 (27)
  • Wall-motion index Median (Range) 0.9 vs 0.9
  • Wall-motion index Range 0.3–1.2 vs 0.3–1.2

Medications at randomization no. (%)

  • Beta-blocker 72 (9) vs 80 (11)
  • ACE inhibitor 571 (76) vs 552 (72)
  • Calcium-channel blocker 153 (20) vs 170 (22)

NYHA functional class no. (%)

  • I 16 (2) vs 17 (2 )
  • II 268 (35) vs 297 (39)
  • III 423 (56) vs 385 (51)
  • IV 49 (6) vs 52 (7)
  • Not available: 5 (<1) vs 6 (<1)

Interventions

  • Screened 5548 CHF admissions for inclusion and exclusion.
  • 4% of patient received multiple screenings resulting in 5812 screenings.
  • 2531 completed an 2D motion echo
  • 1518 patients underwent randomization
    • 762 received Dofetilide
    • 756 received placebo

Follow-Up

  • 1 months after initiation of therapy
  • 3 months after initiation of therapy
  • Then every 3 months until the 12 months after last patient enrollment.

Median follow-up

  • 18 months

Outcomes

Comparisons are INTERVENTION 1 vs. INTERVENTION 2.

Primary Outcomes

PRIMARY OUTCOME
##% vs. ##% (HR ##; 95% CI ##-##; P=##)

Secondary Outcomes

Subgroup Analysis

Adverse Events

Criticisms

Funding

Further Reading