Key Points:
The global burden of hypertension (HTN) with high globally at 1.3 billion people and locally in India with 300 million affected
Despite making up 25% of the global population, there has never been a randomized controlled trial to investigate the optimal initial guideline-recommended combination therapy to treat HTN in those of Indian ancestry
Nearly 2000 patients were randomized to one of the three recommended initial HTN combination therapies to determine the mean change in 24-hour ambulatory systolic blood pressure (SBP) as well as other secondary outcomes
All three groups demonstrated a 14mmHg reduction in ambulatory SBP, suggesting that any of the three recommended combination therapies is reasonable for initial HTN treatment in patients of Indian ancestry
Hypertension (HTN) is a leading preventable cause of cardiovascular morbidity and mortality, affecting 1.3 billion people and responsible for one in five deaths. In India, 300 million individuals are affected by HTN. Disparities exist between rural and urban centers regarding blood pressure (BP) control: only 7-11% of rural populations experience BP control compared to 11-20% of urban populations.
Current HTN guidelines recommend combination therapy with anti-hypertensives from two different classes, specifically renin-angiotensin-aldosterone (RAAS) inhibitors, calcium channel blockers (CCB), or diuretics, particularly as a single-pill combination. Though studies have previously been conducted on other demographics to determine the optimal initial combination therapy, there has been no such randomized controlled trial on South Asian patients, despite making up about 25% of the global population. Therefore, the TOPSPIN study investigated which of the three first-line combination therapies (angiotensin-converted enzyme [ACE] inhibitors plus either CCB or thiazide-like diuretic and CCB plus thiazide-like diuretic) most effectively lowered ambulatory systolic blood pressure (SBP) in Indian patients with uncontrolled HTN.
The TOPSPIN trial was a randomized, single-blind, parallel-group, three arm trial conducted among 35 secondary and tertiary clinics across India with primary care feeder clinics. Study participants ultimately included 1981 Indian adults aged 30-79 with office-based SBP of 140-159mmHg on one anti-hypertensive or SBP of 150-179 on no medical therapy. Patients with coronary artery disease (CAD), stroke, heart failure (HF), secondary HTN, or pregnancy were excluded. The trial randomized participants to one of three groups: amlodipine plus peridopril, amlodipine plus indapamide, or perindopril plus indapamide at initial doses. After two months, therapy was increased to full doses unless SBP was < 120 mmHg. The primary outcome of interest was difference in mean change in 24-hour ambulatory SBP after six months, while secondary outcomes included ambulatory daytime, nighttime, and diastolic BP, office BP, laboratory parameters, and adverse effects leading to termination of medical therapy.
The trial found that all three groups demonstrated a 14mmHg reduction in ambulatory SBP with no significant differences between groups. Office SBP reduced by about 30mmHg and DBP by about 14mmHg, also with no significant differences between groups. In addition, among all three groups, over 40% of participants achieved BP < 130/80, and over 70% achieved BP < 140/90. Regarding adverse effects, 51 participants reported termination of medical treatment due to unusual adverse effects associated with the individual drug classes.
The study investigators concluded that all three guideline-recommended initial HTN combination therapies (ACE-inhibitor plus CCB, ACE-inhibitor plus thiazide-like diuretics, and CCB plus thiazide-like diuretic) all demonstrated equal efficacy among Indian patients with HTN with minimal adverse effects. As such, any of these combination therapies is a reasonable recommendation for initial ambulatory care of a patient of Indian ancestry with HTN and few comorbidities.