Single pill regimen improves persistence and leads lo better clinical outcome compared to identical multi pill combination. Results of START, a German claims data analysis
Authors: Predel H.G , Weisser B , Schmieder R.E , Wassmann S , Blettenberg J , Gillessen A , Fournier V , Noetel A , Randerath O , Boehm M 
Published: November 2020

Abstract

Background/Introduction
The current ESC/ESH-Guidelines for the treatment of arterial hypertension (AH) recommend initiation and escalation of medical treatment using renin–angiotensin–aldosterone system (RAAS) blocker, diuretics (D) and/or calcium channel blockers (CCB). They also recommend a single pill (SP) regimen to improve persistence, to increase blood pressure control and to reduce cardiovascular events.

Purpose
Data showing an advantage for a SP regimen compared to the identical loose combination (LC) regarding all these parameters in a single study are missing. We report now the results comparing SP with identical LC regarding persistence and cardiovascular outcomes in daily practice.

Methods
This was a retrospective, non-interventional analysis of an anonymized claims dataset covering patients suffering from cardiovascular diseases insured by the German AOK PLUS public health insurance in the years 2012–2017. Patients at age ≥18 years with an indication for the use of a combination of RAAS-blockers, D and/or CCB as SP or identical LC were followed up for 1 year. After 1:1-Propensity Score Matching (PSM) persistence (defined as redemption of prescription with a lack &gt;60 days) and clinical outcomes were compared using non-parametric tests.

Results
After PSM, baseline characteristics were comparable between SP and LC groups. Each group included 10,801 patients with valsartan/amlodipine, 1,026 with candesartan/amlodipine, 1,823 with amlodipine/valsartan/hydrochlorothiazide (HCT), and 15,349 with ramipril/amlodipine as SP or identical LC. 8 clinical outcomes were compared for each combination. Persistence to treatment was significant higher in the SP group. In 27 of 32 comparisons a significantly lower Incidence Rate Ratio (IRR) was identified for SP. This was confirmed by time-to-event-analysis. The largest patient group (ramipril/amlodipine) showed a significant lower risk for SP observed for stroke (IRR=0.746; 95% CI 0.627–0.886; p&lt;0.001), transitory ischemic attack (IRR=0.693; 95% CI 0.496–0.963; p=0.023), myocardial infarction (IRR=0.623; 95% CI 0.493–0.784; p&lt;0.001), coronary artery disease (IRR=0.579; 95% CI 0.462–0.723; p&lt;0.001), heart failure (IRR=0.468; 95% CI 0.409–0.534; p&lt;0.001), all cause hospitalization (IRR=0.670; 95% CI 0.652–0.687; p&lt;0.001), cardiovascular hospitalization (IRR=0.596; 95% CI 0.519–0.685; p&lt;0.001), and all cause mortality (IRR=0.526; 95% CI 0.463–0.596; p&lt;0.001) compared to LC.

Conclusion
A SP regimen improves persistence to medication, reduces cardiovascular events and total mortality compared to identical LC. The results of the START study strongly support the use of a SP concept in the AH medication treatment as recommended by the current ESH/ESC-Guidelines for the treatment of AH.

Funding Acknowledgement
Type of funding source: None