ARBs vs ACEIs patients post-MI or at high risk of CVD

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Dickstein K, et al. Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Lancet 2002;360:752-60.

The ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008;358:1547-59.

VALIANT: Pfeffer MA, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003;349:1893-906.

Bottom line:

  • In patients post-MI or at high risk of CVD, telmisartan & valsartan generally prevent CV events as well as ACE inhibitors with similar safety;

  • The combination of ACEI+ARB is no better than monotherapy & increases the risk of adverse events (e.g. hypotension, hyperkalemia & renal impairment);

  • Losartan is inferior to captopril for prevention of CV events.

 

Patients

Interventions

  • OPTIMAAL: ARB vs ACEI
    • ARB: Losartan started at 12.5 mg PO daily; increased to target 50 mg PO daily
      • 83% achieved target dose
    • ACEI: Captopril started at 12.5 mg PO TID; increased to target 50 mg PO TID
      • 81% achieved target dose
  • ONTARGET: ARB, ACEI or combination of both
    • ARB: Telmisartan started at 20 mg PO daily; increased to target 80 mg PO daily
      • 87% achieved target dose
    • ACEI: Ramipril started at 2.5 mg PO daily; increased to target 10 mg PO daily (HOPE dose)
      • 82% achieved target dose
  • VALIANT: ARB, ACEI or combination of both
    • ARB: Valsartan started at 20 mg PO BID; increased to target 160 mg PO BID
    • ACEI: Captopril started at 6.25 mg PO TID; increased to target 50 mg PO TID
    • 56% in each monotherapy group achieved target dose, 47% in combination group achieved target doses

Results @ 2-4.7 years

Generalizability & internal validity

  • Design of these trials essentially identical to the original 'ACEI vs placebo' trials that they mimic
    • I.e. high-quality allocation-concealed double-blind RCTs
  • All 3 trials are non-inferiority trials with fair non-inferiority margins and analyses
    • Note: OPTIMAAL is the only of the 3 that does not demonstrate of the ARB (losartan) & in fact points towards significant inferiority to an ACEI
  • As with the 'ACEI vs placebo' RCTs, results of these trials apply to patients that are post-MI, especially those with clinical HF & LV dysfunction, and those at high risk of CVD