The Single Pill Concept Leads To Improved Persistence Of Medication, Clinical Outcomes And Reduced All-Cause Mortality In Hypertensive Patients - Results From The Start Project

Objective: ESC/ESH guidelines for the treatment of arterial hypertension recommend to start treatment with a single pill combination (SP) of a renin–angiotensin–system (RAS) blocker with a diuretic or a calcium channel blocker to improve drug persistence, blood pressure (BP) control and to reduce cardiovascular events. Escalation should be a SP triple combination. We aimed to assess whether the SP concept is superior to identical free combinations (FC) in terms of clinical outcomes, including all-cause mortality. Design and method: This exploratory analysis of an anonymized claims dataset from patients with hypertension and cardiovascular disease captured in the database of the governmental health insurance company (German AOK PLUS) in the years 2012–2017. 57,998 Patients aged 18 years and older treated with SP or identical FC were followed up for at least 1 year. After 1:1-Propensity Score Matching (PSM) persistence (redemption of prescription with a lack > 60 days) and clinical outcomes were compared using non-parametric tests. Results: No significant differences in baseline characteristics were observed after PSM. 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 FC. Eight different clinical outcomes were compared for each combination. In 27 of 32 comparisons, significantly lower incidence rate ratios (IRR) were identified for SP, confirmed by time-to-event-analyses. In the largest group (ramipril/amlodipine, n = 15,349), a significantly lower risk for stroke (IRR = 0.75; 95% CI 0.627–0.886; p < 0.001), transitory ischemic attack (IRR = 0.69; 95% CI 0.496–0.963; p = 0.023), myocardial infarction (IRR = 0.62; 95% CI 0.493–0.784; p < 0.001), coronary artery disease (IRR = 0.58; 95% CI 0.462–0.723; p < 0.001), heart failure (IRR = 0.47; 95% CI 0.409–0.534; p < 0.001), all cause hospitalization (IRR = 0.67; 0.652–0.687; p < 0.001), cardiovascular hospitalization (IRR = 0.60; 95% CI 0.519–0.685; p < 0.001), and all-cause mortality (IRR = 0.53; 95% CI 0.463–0.596; p < 0.001) was observed for SP versus FC. Conclusions: These results strongly support the ESC/ESH guidelines recommending the use of a SP in favor of FC to improve cardiovascular outcomes including all-cause mortality.