Persistence to antihypertensive drug classes in uncomplicated hypertension: a nationwide Swedish cohort study

Background: Only half of patients appear adherent to antihypertensive treatment. If so, the effectiveness in prevention against adverse cardiovascular outcomes may depend more on a drugs' side effects than its blood pressure effects. We hypothesized that initiating treatment with a particular antihypertensive drug class will determine later persistence. Methods: We applied a new-user trial emulation approach to multiple mandatory health-care registers in Sweden. All individuals starting antihypertensive treatment with an angiotensin receptor blocker (ARB), angiotensin converting enzyme inhibitor (ACEi), calcium channel blocker (CCB), thiazide/thiazide-like diuretic (TD), or single-pill combination of two drugs (SPC) in 2011-2018 were assessed for inclusion. Patients with prior cardiovascular disease or diabetes were excluded. Persistence was defined using dispensed prescription refills with at least 80% adherence. We applied multistate Poisson regression models adjusting for age, sex, obesity, birth country, education, income, marital status and year of initiation. The study period was January 1st 2011-December 31st 2019. Findings: A total of 341,182 patients were included. Initiating antihypertensive treatment with an ARB was associated with a larger proportion continuing their original drug class, or indeed any antihypertensive drug class, at any time during the five years of follow-up. At three years, 44.7% (CI 43.7-45.7) of the ARB initiators were continuously persistent to their original drug class. The corresponding number if intermittent discontinuations were allowed was 81.8% (CI 80.9-82.8). Overall, if intermittent discontinuations and changes between classes were allowed, about 80% of all new users of antihypertensive drugs (regardless of class at initiation) were persistent to at least one antihypertensive drug class over 5 years. Interpretation: Initiating treatment with an ARB is associated with the best long-term class persistence and least treatment changes. The "rule of halves" should be replaced with the insight that, after the first year, at least 4 out of 5 patients take their antihypertensive drug at least 4 out of 5 days. Funding: The study was funded by Anders Wiklöf, Region Uppsala Primary Health and Care, and the Geriatric Foundation, Uppsala Sweden. The computations were enabled by resources in project sens2020005 and sens2020598 provided by the Swedish National Infrastructure for Computing (SNIC) at UPPMAX, partially funded by the Swedish Research Council through grant agreement no. 2018-05973.