Single pill treatment in daily practice is associated with improved clinical outcomes and all-cause mortality in cardiovascular diseases: results from the START project
Authors: Weisser B , Wilke T , Predel H G , Schmieder R E , Wassmann S , Gillessen A , Blettenberg J , Maywald U , Randerath O , Mevius A , Boehm M 
Published: October 2022

Abstract

Objective
Current guidelines for the management of arterial hypertension, dyslipidemia, or secondary cardiovascular (CV) prevention recommend combination drug treatments with single pill combinations (SPC). This concept is expected to improve adherence to treatment and, as a consequence, to reduce the risk of adverse CV outcomes associated with these clinical conditions. Aim of our study was to assess whether SPC are clinically superior to multi pill combination (MPC) with identical drugs in reducing CV events and al-cause mortality in a huge population under real world conditions in daily practice.

Methods
We analyzed an anonymized claims dataset (AOK PLUS, a statutory German sickness fund) including patients with hypertension and other CV diseases in the years 2012–2017; minimum follow-up was 1 year or until date of death, After 1:1-Propensity Score Matching (PSM), selected CV outcomes (myocardial infarction, stroke, transitory ischemic attack, coronary artery disease, heart failure, acute renal failure, cardiovascular hospitalization, all cause hospitalization) as well as all-cause mortality were compared using Incidence Rate Ratios (IRRs) and non-parametric tests.

Results
50,622 patients (25,311 patients in SPC versus MPC group) aged ≥18 years treated with SPC or identical MPC were followed up for at least 1 year or until death. No significant differences in baseline characteristics were observed after PSM. Nine different clinical outcomes were compared for each group. In all comparisons, significantly lower incidence rate ratios (IRR) were identified for SPC, confirmed by comparison of Kaplan-Meier estimates: stroke (IRR=0.77; 95% CI 0.67–0.88; p&lt;0.001), transitory ischemic attack (IRR=0.61; 95% CI 0.48–0.78; p&lt;0.001), myocardial infarction (IRR=0.76; 95% CI 0.63–0.90; p=0.0016), coronary artery disease (IRR=0.66; 95% CI 0.57–0.77; p&lt;0.001), heart failure (IRR=0.59; 95% CI 0.54–0.64; p&lt;0.001), acute renal failure (IRR=0.54; 95% CI 0.56–0.64; p&lt;0.001) all cause hospitalization (IRR=0.72; 95% CI 0.71–0.74; p&lt;0.001), cardiovascular hospitalization (IRR=0.63; 95% CI 0.57–0.69; p&lt;0.001), and all-cause mortality (IRR=0.62; 95% CI 0.57–0.68; p&lt;0.001). The mean time to first events and time to death were also in favor to SPC (any event: SPC 966.052 days/median 873; MPC 846.936 days/median 647; death: SPC 1,719.424 days; MPC 1,657.248 days; log rank for both comparisons: p&lt;0.001).

Conclusion
In clinical practice, the SPC regimen is associated with a lower incidence of CV events and lower all-cause mortality. Time to the event is also significantly longer in the SPC group compared to MPC. These results strongly support the concept of SPC and the implementation into daily practice to improve patient's prognosis.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): APONTIS PHARMA GmbH & Co. KG