Association of Low-Dose Triple Combination Therapy vs Usual Care With Time at Target Blood Pressure
Authors: Sonali R. Gnanenthiran, Nelson Wang, Gian Luca Di Tanna, Abdul Salam, Ruth Webster, H. Asita de Silva, Rama Guggilla, Stephen Jan, Pallab K. Maulik, Nitish Naik, Vanessa Selak, Simon Thom, Dorairaj Prabhakaran, Aletta E. Schutte, Anushka Patel, Anthony Rodgers, Keshinie Samarasekara, Chiranthi Kongala Liyanage, Verni Sopan, Wasantha Kumara, Hansika Pathirana, Lumbini Perera, Manisha Somasiri, Aruna Wijesinghe, Jayamini Jayantha, Sonali Liyanagamage, Muditha de Silva, Chandika Jayawardena, Dilini Karunarathna, Mitrakrishnan Rayno Navinan, Zumra Shukri, Charitha Herath, Nadeeja Seneviratne, Amila Isurangana, Zulaiha Liyakath, Thamal Dasitha, Gerald Rajakulenthiran, Aaisha Azam, Manori Jayawardena, Vinodhan Sunderalingam, Milinda Withana, Anushiya Annaraja, Keshini Soza, Dulani Dasanayake, Dhanushka de Silva, Shakoor Niyasdeen, Uthpala Chandradeva, Safiya Fathima, Aruna Jayawardana, Ranasinghe Chathurika, Manik de Mel, Tharini Mendis, Saumya Withanage, Kandula Pieris, Gayathri Fernando, Chamila Mettanda, Eshani de Silva, Imali Wijerathna, Jeevaraj Thanushanthan, Devaki Dharmawardena, Shehan Gnanapragasam, Shalomi Weerawardena, Matheesha Suduwelikandage, Ingrid de Silva, Sachini Wathsala, Ruchiranga Ekanayaka, Anuradha Dahanayaka, Vindhya Fernando, Lakmal Jayaweera, Namal Wijesinghe, Murali Dhakshinamurthy, Ullas Arabhavi, Harish Sankarankutty, Mohammed Muddaseer, Sarath Gudivada, Aditi Moitra, Ayesha Tazeen, Karuna Acharya, Prakash Velappan, Ambika Yoganathan, Vipin Jose
Journal: JAMA Cardiology (2022)

Cumulative exposure to high blood pressure (BP) is an adverse prognostic marker. Assessments of BP control over time, such as time at target, have been developed but assessments of the effects of BP-lowering interventions on such measures are lacking.To evaluate whether low-dose triple combination antihypertensive therapy was associated with greater rates of time at target compared with usual care.The Triple Pill vs Usual Care Management for Patients With Mild-to-Moderate Hypertension (TRIUMPH) trial was a open-label randomized clinical trial of low-dose triple BP therapy vs usual care conducted in urban hospital clinics in Sri Lanka from February 2016 to May 2017. Adults with hypertension (systolic BP >140 mm Hg and/or diastolic BP >90 mm Hg or in patients with diabetes or chronic kidney disease, systolic BP >130 mm Hg and/or diastolic BP >80 mm Hg) requiring initiation (untreated patients) or escalation (patients receiving monotherapy) of antihypertensive therapy were included. Patients were excluded if they were currently taking 2 or more blood pressure-lowering drugs or had severe or uncontrolled blood pressure, accelerated hypertension or physician-determined need for slower titration of treatment, a contraindication to the triple combination pill therapy, an unstable medical condition, or clinically significant laboratory values deemed by researchers to be unsuitable for the study. All 700 individuals in the original trial were included in the secondary analysis. This post hoc analysis was conducted from December 2020 to December 2021.Once-daily fixed-dose triple combination pill (telmisartan 20 mg, amlodipine 2.5 mg, and chlorthalidone 12.5 mg) therapy vs usual care.Between-group differences in time at target were compared over 24 weeks of follow-up, with time at target defined as percentage of time at target BP.There were a total of 700 randomized patients (mean [SD] age, 56 [11] years; 403 [57.6%] women). Patients allocated to the triple pill group (n = 349) had higher time at target compared with those in the usual care group (n = 351) over 24 weeks' follow-up (64% vs 43%; risk difference, 21%; 95% CI, 16-26; P < .001). Almost twice as many patients receiving triple pill therapy achieved more than 50% time at target during follow-up (64% vs 37%; P < .001). The association of the triple pill with an increase in time at target was seen early, with most patients achieving more than 50% time at target by 12 weeks. Those receiving the triple pill achieved a consistently higher time at target at all follow-up periods compared with those receiving usual care (mean [SD]: 0-6 weeks, 36.3% [30.9%] vs 21.7% [28.9%]; P < .001; 6-12 weeks, 55.2% [31.9%] vs 33.7% [33.0%]; P < .001; 12-24 weeks, 66.0% [31.1%] vs 43.5% [34.3%]; P < .001).To our knowledge, this analysis provides the first estimate of time at target as an outcome assessing longitudinal BP control in a randomized clinical trial. Among patients with mild to moderate hypertension, treatment with a low-dose triple combination pill was associated with substantially higher time at target compared with usual care.