Prevalence and Incidence of Dyskalemia in Hypertensive Patients Initiating a Fixed Dose Combination Pill of Telmisartan and Amlodipine

Hypertension affects an estimated 1.04 billion people in low- and middle-income countries, with an estimated increase in prevalence of 7.7% between 2000 and 2010.1 Hypertension treatment and control may lower the risk of cardiovascular disease and mortality by 20-40%.2 However, less than 10% of individuals with hypertension are under control in low- and middle-income countries, contributing to substantial morbidity and mortality.1 The low prevalence of controlled hypertension may be partly because the vast majority (85.5%) of hypertensive individuals in low- and middle-income countries receive a monotherapy,3 although two or more medications are often needed to achieve a target blood pressure.4 Fixed dose combination (FDC) pills, combining 2 or more classes of antihypertensive medications have considerable appeal because these may reduce blood pressure (BP) more effectively and efficiently compared to monotherapy by blocking two pathways contributing to hypertension.5 Systematic reviews and meta-analyses have shown that FDC pills decreased the risk of non-compliance by 26% compared with free-drug component regimen, while keeping the same rate of reduction in the risk of cardiovascular events.6,7 However, many effective FDC antihypertensive medications include either or both thiazide/thiazide-like diuretic and a renin-angiotensin system inhibitor (RASI) and use of these medications alone, or in combination, generally require laboratory tests to monitor serum potassium. The principal metabolic concern is a risk of incident 'dyskalemia', the occurrence of either hypo- or hyper-kalemia: diuretic-induced hypokalemia and RASI-induced hyperkalemia. Practice guidelines commonly recommend laboratory testing prior to initiation of these drugs, alone or as part of FDC, and periodic monitoring during medication treatment, but guidelines are extremely inconsistent8,9 and are not routinely implemented.10,11 The requirement for laboratory testing is an impediment to implementing FDC in low- and middle-income countries. Therefore, this study will quantify the risk (i.e., prevalence and incidence) of dyskalemia in the context of FDC medication as initial therapy. The study is designed to implement a promising FDC antihypertensive medication of angiotensin receptor blocker (ARB, telmisartan) and calcium channel blocker (CCB, amlodipine) in Bangladesh clinics in collaboration among the National Heart Foundation of Bangladesh, Resolve to Save Lives, and Johns Hopkins University.

Objectives:

• To estimate the prevalence of dyskalemia in hypertensive patients who are candidates for pharmacotherapy.
• Of those patients initiating antihypertensive medication, estimate the incidence of dyskalemia at two months after initiating an FDC combining telmisartan 40 mg/amlodipine 5 mg.

Study Design:

This study will be pre-post study design. This design is chosen because the incidence of dyskalemia is reasonably considered attributable to the initiation of FDC medication, given the short follow-up period (i.e., the only change is the initiation of FDC medication in the exposure status, and it is unlikely that other significant changes in medical and health conditions occur and subsequently impact the incidence of dyskalemia). Because each individual can serve as both control and treatment (i.e., the prevalence of dyskalemia will serve as the control), the pre-post design will be efficient to address this research question while reserving the scientific rigor, compared to randomized control trials, which would require a much larger sample size.