Improving hypertension control with a strategy of early use of lowdose combination of blood pressure lowering drugs

Abstract

Hypertension is a leading public health problem globally, particularly in low- and middle-income countries. The current approach to pharmacological management of hypertension has limitations and may contribute to poor hypertension control. A strategy of early use of lowdose combination therapy may improve outcomes but there is uncertainty about its potential effects. Methods Epidemiology of hypertension in India and Sri Lanka was described. Systematic reviews and meta-analyses were conducted to quantify the dose-related efficacy and safety of combination BP lowering drugs. Data from qualitative interviews of providers and patients were analysed to explore barriers to use of preventive drugs for CVD and acceptability of combination therapy as a solution to key barriers. Data from a large study in rural India were analysed to model the potential benefits of early use of low-dose triple combination therapy at a population level. Results The prevalence of uncontrolled hypertension among adults in India and Sri Lanka is currently estimated to be >70%. Meta-analyses of RCTs showed that compared to placebo, initial therapy with low-dose dual combination reduced BP by 10.1/5.9 mm Hg, whereas low-dose triple combination, tested as replacement therapy in only one trial, reduced BP by 17.9/9.8 mm Hg. Low-dose triple combination therapy vs. one std. dose monotherapy reduced BP by about 10/4 mm Hg. While there was no clear difference in tolerability between low-dose dual or triple combination therapies compared to placebo, data were sparse. From a patient and provider perspective, complex regimens and cost of drugs are major barriers to use of prescribed drugs. The use of combination therapy to simplify drug regimens and reduce cost was highly acceptable. The protocol for a new trial to address relevant evidence gaps is described. If the anticipated effects of this trial were applied at a population level the strategy of early use of low-dose combination therapy compared to the stepped care therapy can reduce BP by 7.8/3.5 mm Hg and improve BP control by 11%. Conclusion A strategy of early use of low-dose triple combination therapy has large potential to improve hypertension control safely and effectively, and is likely to be cost-effective whilst being acceptable to patients and providers. However, current data are insufficient and the ongoing TRIUMPH study will provide more definitive evidence.