Estimated impact of guidelines-based initiation of dual antihypertensive therapy on long-term cardiovascular outcomes in 1.1 million individuals

Abstract

Aims: Guidelines recommend initiation of dual combination antihypertensive therapy, preferably single-pill combination (SPC), in most patients with hypertension. Evidence on narrowing gaps in clinical practice relative to guidelines is limited.

Methods and results: Monte Carlo simulation was applied to 1.1 million patients qualifying for dual combination therapy from a previously conducted retrospective analysis of clinical practice, hospital statistics, and national statistics in the UK. We provide 10-year Kaplan-Meier event rates for the primary endpoint representing a composite of non-fatal myocardial infarction, non-fatal stroke (ischaemic or haemorrhagic), non-fatal heart failure hospitalization, or cardiovascular death. Cox model results from a previously conducted study were utilized to estimate baseline risk, together with evidence on risk reduction from the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) meta-analysis and published evidence on blood pressure-lowering efficacy of antihypertensive therapies. In the overall population, estimated 10-year event rates for the primary endpoint in patients with 100% persistence in monotherapy were 17.0% for irbesartan and 17.6% for ramipril. These rates were only modestly better than those observed in clinical practice (17.8%). In patients with 100% persistence in dual therapy, estimated event rates were 13.6% for combinations of irbesartan + amlodipine [absolute risk reduction (ARR) = 8.7% compared with untreated] and 14.3% for ramipril + amlodipine (ARR = 8.0% compared with untreated). The absolute risk of the primary endpoint was reduced by 15.9% in patients with atherosclerotic cardiovascular disease (ASCVD) and 6.6% in those without ASCVD. Similarly, the absolute risk was reduced by 11.7% in patients with diabetes and 7.8% in those without diabetes.

Conclusions: This study represents the first to investigate guidelines-based treatment in hypertensive patients and demonstrates the opportunity for considerable risk reduction by ensuring recommended dual therapy in clinical practice, particularly in the form of SPC with high persistence, relative to no treatment or monotherapy.

Keywords: Cardiovascular risk; Clinical practice guidelines; Dual therapy; Event rates; Hypertension; Simulation.