Anglo-Scandinavian Cardiac Outcomes Trial - Blood Pressure Lowering (ASCOT -BPLA)

• the Anglo-Scandinavian Cardiac Outcomes Trial - Blood Pressure Lowering Arm (ASCOT-BPLA) results were published in September 2005 (1)
  • ASCOT-BPLA was a randomised controlled trial that included 19,257 patients aged 40-79 years with hypertension and with at least three additional risk factors for cardiovascular (CV) disease (e.g. age >55 years, male, smoker, microalbuminuria or proteinuria, type 2 diabetes)
  • patients with prior myocardial infarction (MI), recent stroke, or treated angina were excluded
  • management of hypertension was based on stepped regimens of a beta-blocker (atenolol) and a thiazide diuretic, or a calcium channel blocker (CCB) (amlodipine) and an angiotensin-converting enzyme (ACE) inhibitor, with further addition of doxazosin, if necessary, to achieve blood pressure (BP)
  • on termination of the study 78% of patients were taking at least two drugs
  • ASCOT-BPLA was stopped early by the data safety monitoring board after a median of 5.5 years when interim analysis showed higher mortality for patients in the atenolol group
  • Results (1):
    • primary endpoint (nonfatal MI plus fatal coronary heart disease CHD) - the trial did not reveal a statistical significance between treatment groups:
      • amlodipine group 4.5%; atenolol group 4.9% (HR 0.90; 95% CI 0.79-1.02)
    • there were significant differences in favour of the amlodipine group found in most secondary endpoints including CV mortality, strokes, and CV events plus procedures
    • fewer patients developed new-onset diabetes in the amlodipine group than in the atenolol group: 5.9% vs. 8.3% (HR 0.70; 95% CI 0.63 - 0.78)
    • 25% of patients in both groups stopped therapy early because of adverse events (AEs)
      • fewer did so because of serious AEs in the amlodipine group compared with the atenolol group (1.7% vs. 2.6%, P<0.0001)
• it has however been stated in a Lancet editorial that the differences in outcomes between groups may be explained by the difference in BP-lowering effects between the two regimens, which averaged 2.7/1.9mmHg during the study (P<0.0001) (2)

Notes:

• ASCOT-BPLA strengthens the case for a more cautious use of beta-blockers (or at least atenolol) as first-line therapy for hypertension, but there may be occasions when this is appropriate, e.g. a patient has CHD (3)
• ASCOT-BPLA confirms that a treatment strategy based on a beta-blocker and diuretic can increase the risk of new-onset diabetes
• ASCOT-BPLA does not diminish the position of thiazide diuretics a highly appropriate first line therapy for many patients with hypertension (4)

Reference:

1. Dahlöf B et al. for the ASCOT investigators. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial - Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet 2005;366:895?906.
2. Staessen JA, Birkenhäger WH. Evidence that new antihypertensives are superior to older drugs. Lancet 2005;366:869?70
3. MeReC Extra (November 2005); 19.
4. Zarnke KB. Commentary. Evidence Based Medicine 2006;11:42.