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CLINICAL STATEMENTS AND GUIDELINES Circulation. 2025;152:e114–e218. DOI: 10.1161/CIR.0000000000001356 September 16, 2025 e153 reasonable treatment strategy for initial pharmaco therapy for stage 1 hypertension.17 This approach remains a reasonable option in older adults and in individuals who have a history of hypotension or multiple drug-associated side effects. 3. High-quality RCT reports demonstrate that simulta neous administration of RAS blockers (ie, an ACEi combined with an ARB or an ACEi or ARB combined with the direct renin inhibitor, aliskiren) increases the risk of CVD, kidney disease, and hyperkalemia.7–9 Additionally, drug combinations with agents that have similar mechanisms of action or clinical effects should be avoided. For example, 2 drugs from the same class should not be administered together (eg, 2 different BB, ACEi, or dihydropyridine CCB). Likewise, 2 drugs from classes that target the same BP control system are less effective and potentially harmful when used together (eg, ACEi and ARB). Exceptions include concomitant use of thiazide-type and potassiumsparing diuretics, and thiazide-type and loop diuret ics. Dihydropyridine and nondihydropyridine CCB can be combined for additional BP-lowering in selected patients. 5.2.5 Antihypertensive Medication Adherence Strategies Recommendations for Antihypertensive Medication Adherence Strategies Referenced studies that support the recommendations are summarized in the Evidence Table. COR LOE Recommendations 1 B-R 1 In adults with hypertension, antihypertensive medication dosing once daily rather than multiple times daily is beneficial to improve medication adherence.1–3 1 B-R 2 In adults with hypertension, the use of a SPC to reduce pill burden rather than taking separate pills is effective to improve medication adherence.4–9 2a B-R 3 In adults with hypertension, use of medication reminder aids and educational or self-management interventions can be useful to improve medication adherence.10–16 Synopsis Studies have documented that up to 50% of patients do not adhere to their antihypertensive medications after 1 year of treatment.17–19 Adherence to medications can be assessed in multiple ways, including self-report, medi cation adherence questionnaires, review of prescription refills, pill counting, electronic pill boxes, and chemical adherence testing of antihypertensive drug levels (Table 15).20–23 Adherence to medication can be divided into 3 phases: 1) initiation; 2) persistence or implementation, consistent with medication taking; and 3) avoiding per manent discontinuation.18,19,21 There are a myriad of factors that contribute to poor adherence, including social determinants of health (SDOH), poor health literacy, stress, anxiety, and depression.21,23–29 Multiple cointerventions are often needed to improve medication adherence. Once nonadherence is identified, clinicians must work with patients to identify barriers to adherence in a nonjudg mental manner and create a plan that includes patient preferences and shared decision-making to overcome obstacles to adherence.30 Patients in whom nonadher ence is identified should be screened for stress, anxi ety, and depression with valid and reliable scales, as studies have found nonadherence rates to be higher in those with these mental health disorders, with referral for appropriate interventions.23–25,27 Screening for low health literacy should also be conducted, and if identi fied, patients can be provided with additional educa tion and resources. Recommendation-Specific Supportive Text 1 Taking medications several times throughout the day requires greater attention to scheduling, trans portation, and storage, which can be challenging for some patients. The impact of once-daily dos ing of antihypertensive medications versus dosing multiple times daily has been evaluated in several meta-analyses.1–3 Medication adherence was great est with once-daily dosing and declined as dosing frequency increased.1–3 Furthermore, a large RCT showed a significantly higher adherence rate among hypertensive adults with morning dosing (6:00 am to 10:00 am) versus evening dosing of once-daily medications.31 2 Assessment and modification of drug therapy regimens can improve suboptimal adherence.1–3,27 Simplifying medication regimens, either by less fre quent dosing (ie, once daily versus multiple times daily) or use of combination drug therapy, improves adherence. Findings from a growing body of sys tematic reviews of nonrandomized controlled trials and observational studies support medication syn chronization (ie, coordinating the refill of medica tions on the same day of each month), especially when dates are appointment-based, as a means to improve adherence.10–12 3 RCTs, systematic reviews, and meta-analyses pro vide evidence that the following interventions can improve adherence: medication reminder aids (eg, text, telephone, smartphone apps); patient education and self-management programs; mindfulness-based stress reduction or counseling for high stress, anxi ety, or depression; simplification of antihypertensive regimen; electronic/home blood pressure monitoring, feedback to clinicians about antihypertensive adher ence via displaying prescription refills or undetected drug levels; and education/coaching by health care professionals.10–15,22,32–34 Downloaded from http://ahajournals.org by on October 7, 2026