Discussion
This is the first large, randomized, double-blind, multicenter study to assess the efficacy and safety of triple therapy for the treatment of moderate or severe hypertension. Triple therapy with Aml/Val/HCTZ produced robust reductions in both MSSBP and MSDBP that were statistically superior to all of the component dual therapies. The observed 3.3- to 5.3- mmHg decreases in MSDBP in favor of triple therapy are clinically significant, because even small reductions in DBP are associated with substantial decreases in cardiovascular risk. For example, a 2-mmHg decrease in DBP has been estimated to reduce the risk of coronary heart disease by 6% and stroke and transient ischemic attack by 15%. In the Valsartan Antihypertensive Long-term Use Evaluation Trial, a small difference in BP reduction (≈4/2 mmHg) between active treatments was associated with a significant difference in the incidences of stroke and all-cause mortality and time to first cardiac evevt.