A multivariable algorithm for perindopril-indapamide in type 2 diabetes found 43% of patients had a predicted 5-year absolute risk reduction of ≥1% (NNT ≤100) for major cardiovascular events.
RCT (n=11,140)
Does a multivariable treatment algorithm predicting absolute risk reduction from perindopril-indapamide improve treatment selection for major adverse cardiovascular events in patients with type 2 diabetes mellitus?
A multivariable treatment algorithm can identify individual patients with type 2 diabetes who benefit most from blood pressure-lowering therapy, optimizing net benefit compared to treat-all or threshold-based strategies.
UNLABELLED: Blood pressure-lowering treatment reduces cardiovascular risk in patients with diabetes mellitus, but the effect varies between individuals. We sought to identify which patients benefit most from such treatment in a large clinical trial in type 2 diabetes mellitus. In Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) participants (n=11 140), we estimated the individual patient 5-year absolute risk of major adverse cardiovascular events with and without treatment by perindopril-indapamide (4/1.25 mg). The difference between treated and untreated risk is the estimated individual patient's absolute risk reduction (ARR). Predictions were based on a Cox proportional hazards model inclusive of demographic and clinical characteristics together with the observed relative treatment effect. The group-level effect of selectively treating patients with an estimated ARR above a range of decision thresholds was compared with treating everyone or those with a blood pressure >140/90 mm Hg using net benefit analysis. In ADVANCE, there was wide variation in treatment effects across individual patients. According to the algorithm, 43% of patients had a large predicted 5-year ARR of ≥1% (number-needed-to-treat NNT5 ≤100) and 40% had an intermediate predicted ARR of 0.5% to 1% (NNT5=100-`200). The proportion of patients with a small ARR of ≤0.5% (NNT5≥200) was 17%. Provided that one is prepared to treat at most 200 patients for 5 years to prevent 1 adverse outcome, prediction-based treatment yielded the highest net benefit. In conclusion, a multivariable treatment algorithm can identify those individuals who benefit most from blood pressure-lowering therapy in terms of ARR of major adverse cardiovascular events and may be used to guide treatment decisions in individual patients with diabetes. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00145925.
Leeuw et al. (Tue,) conducted a rct in Type 2 diabetes mellitus (n=11,140). perindopril-indapamide vs. without treatment was evaluated on Major adverse cardiovascular events. A multivariable algorithm for perindopril-indapamide in type 2 diabetes found 43% of patients had a predicted 5-year absolute risk reduction of ≥1% (NNT ≤100) for major cardiovascular events.