Heart failure The national burden

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Heart failure: The national burden

    • Affects 1 million Americans
    • >550,000 new cases annually
    • >53,000 deaths in 2002
    • Leading Medicare hospital diagnosis
    • >1 million hospitalizations annually
    • Direct and indirect costs: $27.9 billion

                          AHA. Heart disease and stroke statistics–2005 update.
                                 Koelling TM et al. Am Heart J. 2004;147:74-8.
ACC/AHA: Heart failure stages A and B
                        Stage A                           Stage B
Definition              No structural heart               Structural heart
                        disease/asymptomatic              disease/asymptomatic

Patients                Hypertension                      Previous MI
                        CAD                               LV remodeling
                        Diabetes                          LV hypertrophy
                        Obesity                           Low EF
                        Metabolic syndrome

Goals                   Treat BP, lipids                  All measures under
                        Smoking cessation                 stage A
                         Regular exercise
                         Alcohol/drug use

Therapy                 ACEI or ARB for vascular          ACEI or ARB*
                        disease/diabetes*                 -Blockers*
*Appropriate patients                              Hunt SA et al. J Am Coll Cardiol. 2005;46:1-82.
ACC/AHA: Heart failure stages C and D
                 Stage C                        Stage D

Definition       Structural heart disease        Refractory HF
                 Prior/current symptoms
Patients         Shortness of breath             Marked symptoms at rest despite
                 Fatigue                         maximal therapy
                 Exercise capacity
Goals            All Stage A and B               All Stage A, B, and C
                 Dietary salt restriction        Decision re: appropriate level of care
Drug             Routine drugs                   Options
therapy           Diuretics                       Compassionate care/hospice
                  ACEI                           Extraordinary measures
                  -Blockers                      Heart transplant
                 Selected patients                Chronic inotropes
                  Aldosterone antagonist          Permanent mechanical support
                  ARBs                            Experimental surgery/drugs
Devices*         Biventricular pacing
                 Implantable defibrillators
*Selected patients                            Hunt SA et al. J Am Coll Cardiol. 2005;46:1-82.
CHARM: HF patients with LV dysfunction

                  CHARM-Alternative           CHARM-Added

   Patients        N = 2028                   N = 2548
                   LVEF ≤40%                  LVEF ≤40%
                   Intolerant to ACEI         Treated with ACEI

   Therapy        Candesartan 32 mg/d         Candesartan 32 mg/d vs placebo
                  vs placebo                  + ACEI and other HF therapy

   Follow-up      41 months                   33.7 months

   Primary         23% RRR (P < 0.001)        15% RRR (P < 0.011)
   outcome*        7% absolute               4% absolute 

*CV mortality/HF hospitalization           Granger CB et al. Lancet. 2003;362:772-6.
RRR = relative risk reduction            McMurray JJV et al. Lancet. 2003;362:767-71.
VALIANT: Study design

 Patients            N = 14,703 with MI within ≤10 days
                     HF and/or LVEF <35%*

 Therapy             Valsartan 160 mg 2/d (n = 4909)
                     Captopril 50 mg 3/d (n = 4909)
                     Captopril 50 mg 3/d + valsartan 80 mg 2/d (n = 4885)

 Follow-up           24.7 months

*<40% by radionuclide ventriculography (RVG)   Pfeffer MA et al. N Engl J Med. 2003;349:1893-906.
VALIANT: Primary outcome—
Death from any cause
                                       Valsartan plus captopril†
                         0.3           Captopril

              of event


                               0   6   12 18 24 30 36
*P = 0.98 vs captopril
†P = 0.73 vs captopril                    Pfeffer MA et al. N Engl J Med. 2003;349:1893-906.
ACC/AHA recommendations:
ARBs in patients with LV dysfunction
                                                    Class             Level of evidence
Alternative therapy:
Use ARBs approved for the treatment
of HF in patients witih current or prior HF               I                      A
symptoms who are ACEI intolerant

ARBs are reasonable alternatives to ACEI as
first-line therapy for patients with mild to
moderate HF, especially those already taking             IIa                     A
ARBs for other indications
ARBs should be administered to post-MI
patients without HF symptoms who are
intolerant of ACEIs and have a low LVEF                   I                      B
Added therapy:
Consider adding ARBs in persistently
symptomatic patients with reduced LVEF who               IIb                     B
are already treated with conventional therapy
                                                Hunt SA et al. J Am Coll Cardiol. 2005;46:1-82.
CHARM-Added: Effects of adding
candesartan to -blocker and ACEI

                             Candesartan   Placebo                                      P*
                                                       Candesartan       Placebo
      -Blocker                                           better          better
               Yes            223/702      274/711
                No            260/574      264/561                                     0.14
      Recommended dose
      of ACE inhibitor
               Yes     232/643             275/648
               No      251/633             263/624                                     0.26

      All patients            483/1276     538/1272

                                                 0.6 0.7 0.8 0.9 1.0 1.1 1.2

                                                             Hazard ratio

*For treatment interaction                            McMurray JVV et al. Lancet. 2003;362:767-71.
HF with LV dysfunction:
Patients, efficacy, and dosing considerations

                                                        Initial          Maximum
ARB           Patients        Efficacy                 dose(s)            dose(s)

Candesartan   HF         CV mortality                 4–8 mg               32 mg
                          HF hospitalizations         1/d                 1/d

Valsartan     HF          CV mortality                20–40 mg             160 mg
              Post-MI                                  2/d                 2/d

                              Adapted from Hunt SA et al. J Am Coll Cardiol. 2005;46:1-82.
CHARM: Prevention of diabetes
with candesartan


                       8        RRR = 22%                       Placebo               n = 202 (7.4%)
    Proportion                  HR = 0.78 (0.64–0.96)
    of patients        6        P = 0.020                                             n = 163 (6.0%)

                           0            1.0              2.0            3.0     3.5

RRR = relative risk reduction                                    Yusuf S et al. Circulation. 2005;112:48-53.