Indirect treatment comparison between fixed-dose-combinations of amlodipine/losartan and amlodipine/valsartan in blood pressure control

Abstract

This study compared blood pressure (BP) changes after 8 weeks of therapy between a fixed-dose combination (FDC) of amlodipine/losartan and amlodipine/valsartan using a network meta-analysis because no trials directly compared amlodipine/losartan with other FDCs. A systematic search identified six randomised controlled trials (amlodipine/losartan-3, amlodipine/valsartan-3) of FDCs and their component monotherapies. Conventional fixed-effects methods were used to conduct the comparisons. The primary and secondary effect measures were the changes in sitting diastolic and systolic blood pressure (sitDBP, sitSBP) at 8 weeks post-randomisation. The estimated amlodipine/valsartan - amlodipine/losartan difference (95% confidence interval) in sitDBP reduction was -1.27 mmHg, (-5.7, 2.2) for lower dosages and -0.45 mmHg, (-3.7, 2.7) for higher dosages; for sitSBP, the values were -3.74 mmHg, (-9.0, 2.9) for lower dosages and 0.2 mmHg, (-6.2, 6.0) for higher dosages. The confidence of a greater reduction in BP (fixed difference = 0) on amlodipine/losartan 5/50 than on amlodipine/valsartan 5/80 was 77% for sitDBP and 89% for sitSBP. The corresponding confidence for the higher doses was 61% for sitDBP and 48% for sitSBP. The findings support asserting with (fixed) 95% confidence that the BP reduction on amlodipine/valsartan 5/80 exceeds the amlodipine/losartan 5/50 reduction by at most 1.6 mmHg for sitDBP, and at most 1.26 mmHg for sitSBP. The corresponding upper bounds for the higher dosages were 2.31 mmHg (sitDBP) and 5.38 mmHg (sitSBP). The BP lowering effect with amlodipine/losartan and amlodipine/valsartan was comparable. Potential superiority of the reductions realised with amlodipine/valsartan relative to amlodipine/losartan, are unlikely to be clinically material.