Fixed low-dose triple combination antihypertensive medication vs usual care for blood pressure control in patients with mild to moderate hypertension in Sri Lanka a randomized clinical trial

IMPORTANCE Poorly controlled hypertension is a leading global public health problem requiring new treatment strategies. OBJECTIVE To assess whether a low-dose triple combination antihypertensive medication would achieve better blood pressure (BP) control vs usual care. DESIGN, SETTING, AND PARTICIPANTS Randomized, open-label trial of a low-dose triple BP therapy vs usual care for adults with hypertension (systolic BP >140mmHg and/or diastolic BP >90mmHg; or in patients with diabetes or chronic kidney disease: >130mmHg and/or >80mmHg) requiring initiation (untreated patients) or escalation (patients receiving monotherapy) of antihypertensive therapy. Patients were enrolled from 11 urban hospital clinics in Sri Lanka from February 2016 toMay 2017; follow-up ended in October 2017. INTERVENTIONS A once-daily fixed-dose triple combination pill (20mg of telmisartan, 2.5mg of amlodipine, and 12.5mg of chlorthalidone) therapy (n = 349) or usual care (n = 351). MAIN OUTCOMES AND MEASURES The primary outcomewas the proportion achieving target systolic/diastolic BP (<140/90mmHg or <130/80mmHg in patients with diabetes or chronic kidney disease) at 6 months. Secondary outcomes included mean systolic/diastolic BP difference during follow-up and withdrawal of BP medications due to an adverse event. RESULTS Among 700 randomized patients (mean age, 56 years; 58%women; 29% had diabetes; mean baseline systolic/diastolic BP, 154/90mmHg), 675 (96%) completed the trial. The triple combination pill increased the proportion achieving target BP vs usual care at 6 months (70% vs 55%, respectively; risk difference, 12.7%[95%CI, 3.2%to 22.0%]; P < .001). Mean systolic/diastolic BP at 6 months was 125/76mmHg for the triple combination pill vs 134/81mmHg for usual care (adjusted difference in postrandomization BP over the entire follow-up: Systolic BP, -9.8 [95%CI, -7.9 to -11.6]mmHg; diastolic BP, -5.0 [95%CI, -3.9 to -6.1] mmHg; P < .001 for both comparisons). Overall, 419 adverse events were reported in 255 patients (38.1%for triple combination pill vs 34.8%for usual care) with the most common being musculoskeletal pain (6.0%and 8.0%, respectively) and dizziness, presyncope, or syncope (5.2%and 2.8%). There were no significant between-group differences in the proportion of patient withdrawal from BP-lowering therapy due to adverse events (6.6%for triple combination pill vs 6.8%for usual care). CONCLUSIONS AND RELEVANCE Among patients with mild to moderate hypertension, treatment with a pill containing low doses of 3 antihypertensive drugs led to an increased proportion of patients achieving their target BP goal vs usual care. Use of such medication as initial therapy or to replace monotherapymay be an effective way to improve BP control.