Three post-hoc analyses were performed to determine whether the difference in achieved blood pressure in the main VALUE trial, reported 1 year ago, affected outcomes or whether there are pharmacologic differences between the study drugs valsartan and amlodipine in this patient population. The analyses evaluated outcomes in the 7080 patients in VALUE who were on monotherapy at 6 months; the mean duration of monotherapy was 3.06 years.°Prof. Stevo Julius°(University of Michigan, USA) reported the monotherapy results at the 15th European Meeting on Hypertension held in Milan, June 17-21.
Blood pressure reduction was the same with both drugs in monotherapy. The effect on outcomes seen in the monotherapy analyses were similar to those in the main study, yet the absolute risk in the monotherapy group was lower.
To determine if outcomes were different with the two study drugs, a censored analysis was performed of the events that occurred during the time period the patient was receiving only monotherapy. This censored analysis showed that valsartan monotherapy, compared to amlodipine monotherapy, produced a significant 37% reduction in heart failure, with only 1.78% of valsartan patients developing heart failure compared to 3.17% of amlodipine patients(p=0.004); a 12% reduction in the composite primary endpoint (p=0.206); and a 23% reduction in new onset diabetes, with 7.78% of valsartan and 9.86% of amlodipine patients developing diabetes (p=0.012). With amlodipine monotherapy, the occurrence of MI, stroke, and all-cause mortality, but these did not reach statistical significance.
An intention-to-treat sensitivity analysis, performed to determine if drug differences affected outcomes, also showed less development of heart failure (p=0.045) and diabetes (p=0.034) with valsartan monotherapy compared to amlodipine monotherapy. The other outcomes were similar to those in the censored analysis.
Another intention-to-treat analysis looked at whether the duration of treatment affected outcomes, and showed that, indeed, there was a greater effect on heart failure with a longer duration of valsartan monotherapy; the difference in effect was seen at 12 months and continued to increase thereafter. Monotherapy with valsartan and amlodipine had a similar effect on MI in this duration analysis.
The combined primary endpoint in VALUE was the time to the first cardiac mortality or morbidity event, defined as sudden cardiac death, fatal myocardial infarction (MI) or evidence of MI on autopsy, death during emergency cardiac revascularization procedures, death from heart failure, non-fatal MI, heart failure hospitalization, emergency cardiac revascularization procedure.