Estimated impact of timely guidelines-based initiation of dual-combination anti-hypertensive therapy on long-term cardiovascular outcomes in a population of 1.4 million individuals

Abstract

Abstract Background In most patients qualifying for anti-hypertensive treatment initiation, guidelines recommend dual-combination therapy. Purpose To estimate cardiovascular (CV) events rate with optimal and suboptimal adoption of guideline-based treatment in comparison with observed risk in a large population representing usual clinical practice. Methods A study population representing real-world clinical practice was developed from the Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics databases in England. Adults qualifying for dual BP-lowering therapy as per the 2018 ESC/ESH guidelines were identified during 15-year period (2005-2019). Primary endpoint was composite of nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, and CV death. A Cox model relating patient characteristics to the risk of primary endpoint was estimated for overall population and subgroups (Atherosclerotic cardiovascular disease [ASCVD] and diabetes). Patients in the real-world cohort entered a Monte-Carlo simulation model which simulated CV events over time consistent with an individual-specific predicted risk from the Cox model based on their characteristics. Following scenarios were investigated: (1) untreated (reference); (2) optimal treatment (full adherence and persistence); (3) suboptimal adherence (50% adherence); (4) suboptimal persistence (50% discontinuation at 1-year). Scenario 5 represented observed clinical practice in databases. Ten-year event rates, ARRs and NNTs were estimated for each scenario with scenario 1. Results The observed 10-year event rate for the primary endpoint representing clinical practice (scenario 5) in the database was 17.8% (Tables 1 and 2). In scenario 2, the simulated 10-year event rates for the primary endpoint were 15.8% (absolute risk reduction [ARR] 6.6%, number needed to treat [NNT] 15) and 15.2% (ARR 7.1%, NNT 14) for Ramipril plus Amlodipine (R+A) and Irbesartan plus Amlodipine (I+A), respectively. In scenario 3, the simulated 10-year event rates for the primary endpoint were 18.8% (ARR 3.6%, NNT 28) and 18.5% (ARR 3.9%, NNT 26), respectively, for R+A and I+A. The most notable risk reductions were seen in ASCVD subgroup for scenario 2; ARR 11.2% and 12.3% for R+A and I+A, respectively. Similarly, in diabetes subgroup scenario 2, resulted in highest ARR (8.2% and 8.7%) and lowest NNT (12 for both), indicating good clinical benefit of treatment. Conclusions These findings indicate substantial opportunity for population-level risk reduction by optimal guidelines-based treatment initiation with dual-combination anti-hypertensive therapy as compared to observed clinical practice. Results suggest substantial population attributable risk for behaviors of suboptimal adherence and persistence. The opportunity for risk reduction by optimal treatment, and attributable risk due to suboptimal treatment, were especially high for individuals with ASCVD or diabetes.Table 1Table 2