CAMELOT - Amlodipine, enalapril or placebo in CAD

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Nissen SE, et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial. JAMA 2004;292:2217-25.

Bottom line: In patients with symptomatic, angiographically-confirmed CAD without heart failure symptoms or LV dysfunction, amlodipine, but not enalapril, reduced the risk of ischemia-driven outcomes, including coronary revascularization (NNT 26) and hospitalization for angina (NNT 20), consistent with its anti-anginal mechanism.

Notably, neither amlodipine or enalapril reduced "hard" clinical outcomes, including death, MI or stroke, compared to placebo over the duration of this trial. This likely reflects a low/intermediate-risk population (e.g. risk of MI ~1.5%/year in placebo group) due to high use of other interventions that reduce CV risk, and short study duration.

 

 

Patients

  • Inclusion:
    • Adults aged 30-79 requiring coronary angiography for evaluation for chest pain or PCI
    • 1 or more lesions in native coronary artery with >20% stenosis
    • Diastolic BP <100 mm Hg by manual BP measurement (could be taking antihypertensives at time of measurement)
  • Exclusion:
    • Moderate-severe HF
    • LVEF <40%
    • Left main coronary artery stenosis >50%
  • 2865 screened -> 1997 randomized -> 1991 analyzed
  • "Average" patient:
    • 58 y
    • Male 75%
    • White 89%
    • Number of coronary arteries with stenosis >20% - 1 (~30%), 2 (~33%), 3 (~35%)
    • BP 129/77
    • PMHx
      • MI 37-40%
      • PCI 26-30%
      • Angina CCS class 4 - 8-9%
      • HTN 60%
      • Diabetes 17-19%
    • Concomitant meds
      • ASA 95%
      • Statin 83%
      • Beta-blocker ~75%
      • Diuretic 26-33%

Generalizability: Who do these results apply to?

  • These results apply to patients with angina and angiographically-confirmed CAD without hypertension, most of whom did not have a previous MI, with no/minimal HF symptoms & normal LVEF
  • These results do not apply to patients who:
    • Qualify for the HOPE or EUROPA trials
    • Have HFrEF, or who are post-MI with LV dysfunction

Interventions

  • Intervention 1: Amlodipine
    • Initial dose: 5 mg PO daily
    • If initial dose tolerated, doubled to 10 mg PO daily at end of week 2
    • If intolerable adverse effect, dose halved & uptitration tried at a later point
    • Titrated to full target dose: 86.7%
    • BP reduced by ~5/2 mm Hg
  • Intervention 2: Enalapril
    • Initial dose: 10 mg PO daily
    • If initial dose tolerated, doubled to 20 mg PO daily at end of week 2
    • If intolerable adverse effect, dose halved & uptitration tried at a later point
    • Titrated to full target dose: 84.3%
    • BP reduced by ~5/2 mm Hg
  • Control: Placebo
  • Co-interventions:
    • Diuretics, alpha-1 blockers, & beta-blockers were permitted
    • Non-study ACEI, ARB & CCBs were not permitted (discontinued over 2-6-week period before study initiation)

Results @ 2 years

  • Statistically significant reduction in the primary outcome with amlodipine, but not enalapril, versus placebo
    • Amlodipine vs placebo: Hazard ratio 0.69 (0.54-0.88)
    • Enalapril vs placebo: HR 0.85 (0.67-1.07)
    • Amlodipine 16.6%, enalapril 20.2%, placebo 23.1%
  • Beneficial effects of amlodipine versus placebo on primary outcome driven by softer, "ischemic" outcomes
    • Coronary revascularization: 11.8% vs 15.7% (NNT 26, p=0.03)
    • Hospitalization for angina: 7.7% vs 12.8% (NNT 20, p=0.002)
  • No statistically significant difference between groups in "hard" clinical outcomes (listed as amlodipine, enalapril, placebo):
    • All-cause mortality, MI or stroke: 3.3%, 3.4%, 4.7%
      • All-cause mortality: 1.1%, 1.2%, 0.9%
      • Non-fatal MI: 2.1%, 1.6%, 2.9%
      • Stroke or TIA: 0.9%, 1.2%, 1.8%
    • Hospitalization for HF: 0.5%, 0.6%, 0.8%
  • Safety:
    • Discontinued study medication: 29.3%, 35.1%, 31.1% (differences between groups not statistically significant, p=0.07)
    • Hypotension: 3.3%, 9.5%, 3.2% (NNH 16 for enalapril vs placebo)
    • Cough: 5.1%, 12.5%, 5.8% (NNH 15 for enalapril vs placebo)
    • Peripheral edema: 32.4%, 9.5%, 9.6% (NNH 5 for amlodipine vs placebo)

Issues with internal validity?

  • No: Randomized, allocation-concealed, blinded (patients, clinicians & outcome adjudicators) trial with low loss-to-follow-up (<0.5%) analyzed using the intent-to-treat population.
  • Notes:
    • Minor baseline imbalances in baseline characteristics, e.g. age (amlodipine 57.3 y vs enalapril 58.5 y) & history of MI (amlodipine 37.4% versus enalapril 40.3%) do not suggest compromised allocation concealment or impact results
    • 2-week placebo run-in period to exclude non-adherent patients (took <80% of doses).