Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item Efficacy and safety of low-dose triple and quadruple combination pills vs monotherapy, usual care, or placebo for the initial management of hypertension: A systematic review and meta-analysis(American Medical Association, 2023) Wang, N.; Rueter, P.; Atkins, E.; Webster, R.; Huffman, M.; de Silva, A.; Chow, C.; Patel, A.; Rodgers, A.IMPORTANCE: Low-dose combination (LDC) antihypertensives consisting of 3 or 4 blood pressure (BP)-lowering drugs have emerged as a potentially important therapy for the initial management of hypertension. OBJECTIVE: To assess the efficacy and safety of LDC therapies for the management of hypertension. DATA SOURCES: PubMed and Medline were searched from date of inception until September 2022. STUDY SELECTION: Randomized clinical trials comparing LDC consisting of 3 or 4 BP-lowering drugs compared to either monotherapy, usual care, or placebo. DATA EXTRACTION AND SYNTHESIS: Data were extracted by 2 independent authors and synthesized using both random and fixed-effects models using risk ratios (RR) for binary outcomes and mean differences for continuous outcomes. MAIN OUTCOMES AND MEASURES: The primary outcome was mean reduction in systolic BP (SBP) between LDC and monotherapy, usual care, or placebo. Other outcomes of interest included the proportion of patients achieving BP less than 140/90 mm Hg, rates of adverse effects, and treatment withdrawal. RESULTS: Seven trials with a total of 1918 patients (mean [mean range] age, 59 [50-70] years; 739 [38%] female) were included. Four trials involved triple-component LDC and 3 involved quadruple-component LDC. At 4 to 12 weeks follow-up, LDC was associated with a greater mean reduction in SBP than initial monotherapy or usual care (mean reduction, 7.4 mm Hg; 95% CI, 4.3-10.5) and placebo (mean reduction, 18.0 mm Hg; 95% CI, 15.1-20.8). LDC was associated with a higher proportion of participants achieving BP less than 140/90 mm Hg at 4 to 12 weeks compared to both monotherapy or usual care (66% vs 46%; RR, 1.40; 95% CI, 1.27-1.52) and placebo (54% vs 18%; RR, 3.03; 95% CI, 1.93-4.77). There was no significant heterogeneity between trials enrolling patients with and without baseline BP-lowering therapy. Results from 2 trials indicated LDC remained superior to monotherapy or usual care at 6 to 12 months. LDC was associated with more dizziness (14% vs 11%; RR 1.28, 95% CI 1.00-1.63) but no other adverse effects nor treatment withdrawal. CONCLUSIONS AND RELEVANCE: The findings in the study showed that LDCs with 3 or 4 antihypertensives were an effective and well-tolerated BP-lowering treatment option for the initial or early management of hypertension.Item Reduced efficacy of blood pressure lowering drugs in the presence of diabetes mellitus-results from the TRIUMPH randomised controlled trial(Nature Publishing Group, 2023) Gnanenthiran, S.R.; Webster, R.; de Silva, A.; Maulik, P.K.; Salam, A.; Selak, V.; Guggilla, R.K.; Schutte, A.E.; Patel, A.; Rodgers, A.; TRIUMPH Study GroupWe investigated whether diabetes mellitus (DM) affects the efficacy of a low-dose triple combination pill and usual care among people with mild-moderate hypertension. TRIUMPH (TRIple pill vs Usual care Management for Patients with mild-to-moderate Hypertension) was a randomised controlled open-label trial of patients requiring initiation or escalation of antihypertensive therapy. Patients were randomised to a once-daily low-dose triple combination polypill (telmisartan-20mg/amlodipine-2.5 mg/chlorthalidone-12.5 mg) or usual care. This analysis compared BP reduction in people with and without DM, both in the intervention and control groups over 24-week follow-up. Predicted efficacy of prescribed therapy was calculated (estimation methods of Law et al.). The trial randomised 700 patients (56 ± 11 yrs, 31% DM). There was no difference in the number of drugs prescribed or predicted efficacy of therapy between people with DM and without DM. However, the observed BP reduction from baseline to week 24 was lower in those with DM compared to non-diabetics in both the triple pill (25/11 vs 31/15 mmHg, p ≤ 0.01) and usual care (17/7 vs 22/11 mmHg, p ≤ 0.01) groups, and these differences remained after multivariable adjustment. DM was a negative predictor of change in BP (β-coefficient -0.08, p = 0.02). In conclusion, patients with DM experienced reduced efficacy of BP lowering therapies as compared to patients without DM, irrespective of the type of BP lowering therapy received.Item Association of low-dose triple combination therapy with therapeutic inertia and prescribing patterns in patients with hypertension: A Secondary analysis of the TRIUMPH trial(American Medical Association., 2020) Wang, N.; Salam, A.; Webster, R.; de Silva, A.; Guggilla, R.; Stepien, S.; Mysore, J.; Billot, L.; Jan, S.; Maulik, P. K.; Naik, N.; Selak, V.; Thom, S.; Prabhakaran, D.; Patel, A.; Rodgers, A.; TRIUMPH Study GroupIMPORTANCE: Fixed-dose combination (FDC) therapies are being increasingly recommended for initial or early management of patients with hypertension, as they reduce treatment complexity and potentially reduce therapeutic inertia. OBJECTIVE: To investigate the association of antihypertensive triple drug FDC therapy with therapeutic inertia and prescribing patterns compared with usual care. DESIGN, SETTING, AND PARTICIPANTS: A post hoc analysis of the Triple Pill vs Usual Care Management for Patients With Mild-to-Moderate Hypertension (TRIUMPH) study, a randomized clinical trial of 700 patients with hypertension, was conducted. Patients were enrolled from 11 urban hospital clinics in Sri Lanka from February 2016 to May 2017; follow-up ended in October 2017. Data were analyzed from September to November 2019. INTERVENTIONS: Once-daily FDC antihypertensive pill (telmisartan, 20 mg; amlodipine, 2.5 mg; and chlorthalidone, 12.5 mg) or usual care. MAIN OUTCOMES AND MEASURES: Therapeutic inertia, defined as not intensifying therapy in those with blood pressure (BP) above target, was assessed at baseline and during follow-up visits. Prescribing patterns were characterized by BP-lowering drug class and treatment regimen potency. Predictors of therapeutic inertia were assessed with binomial logistic regression. RESULTS: Of the 700 included patients, 403 (57.6%) were female, and the mean (SD) age was 56 (11) years. Among patients who did not reach the BP target, therapeutic inertia was more common in the triple pill group compared with the usual care group at the week 6 visit (92 of 106 [86.8%] vs 124 of 194 [63.9%]; P < .001) and week 12 visit (81 of 90 [90%] vs 116 of 179 [64.8%]; P < .001). At the end of the study, 221 of 318 patients in the triple pill group (69.5%) and 182 of 329 patients in the usual care group (55.3%) reached BP targets. Among those who received treatment intensification, the increase in estimated regimen potency was greater in the triple pill group compared with the usual care group at baseline (predicted mean [SD] increase in regimen potency: triple pill, 15 [6] mm Hg; usual care, 10 [5] mm Hg; P < .001), whereas there were no significant differences at the week 6 or at week 12 visit. Clinic systolic BP level was the only consistent predictor of treatment intensification during follow-up. During follow-up, there were 23 vs 54 unique treatment regimens per 100 treated patients in the triple pill vs usual care groups, respectively (P < .001). CONCLUSIONS AND RELEVANCE: Triple pill FDC therapy was associated with greater rates of therapeutic inertia compared with usual care. Despite this, triple pill FDC therapy substantially simplified prescribing patterns and improved 6-month BP control rates compared with usual care. Further improvements in hypertension control could be achieved by addressing therapeutic inertia among the minority of patients who do not achieve BP control after initial FDC therapy.Item Fixed-combination, low-dose, triple-pill antihypertensive medication versus usual care in patients with mild-to-moderate hypertension in Sri Lanka: a within-trial and modelled economic evaluation of the TRIUMPH trial.(The Lancet. Global health., 2019) Lung, T.; Jan, S.; de Silva, H.A.; Guggilla, R.; Maulik, P.K.; Naik, N.; Patel, A.; de Silva, A.P.; Rajapakse, S.; Ranasinghe, G.; Prabhakaran, D.; Rodgers, A.; Salam, A.; Selak, V.; Stepien, S.; Thom, S.; Webster, R.; Lea-Laba, T.; TRIUMPH Study Group.BACKGROUND: Elevated blood pressure incurs a major health and economic burden, particularly in low-income and middle-income countries. The Triple Pill versus Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) trial showed a greater reduction in blood pressure in patients using fixed-combination, low-dose, triple-pill antihypertensive therapy (consisting of amlodipine, telmisartan, and chlorthalidone) than in those receiving usual care in Sri Lanka. We aimed to assess the cost-effectiveness of the triple-pill strategy. METHODS: We did a within-trial (6-month) and modelled (10-year) economic evaluation of the TRIUMPH trial, using the health system perspective. Health-care costs, reported in 2017 US dollars, were determined from trial records and published literature. A discrete-time simulation model was developed, extrapolating trial findings of reduced systolic blood pressure to 10-year health-care costs, cardiovascular disease events, and mortality. The primary outcomes were the proportion of people reaching blood pressure targets (at 6 months from baseline) and disability-adjusted life-years (DALYs) averted (at 10 years from baseline). Incremental cost-effectiveness ratios were calculated to estimate the cost per additional participant achieving target blood pressure at 6 months and cost per DALY averted over 10 years. FINDINGS: The triple-pill strategy, compared with usual care, cost an additional US$9·63 (95% CI 5·29 to 13·97) per person in the within-trial analysis and $347·75 (285·55 to 412·54) per person in the modelled analysis. Incremental cost-effectiveness ratios were estimated at $7·93 (95% CI 6·59 to 11·84) per participant reaching blood pressure targets at 6 months and $2842·79 (-28·67 to 5714·24) per DALY averted over a 10-year period. INTERPRETATION: Compared with usual care, the triple-pill strategy is cost-effective for patients with mild-to-moderate hypertension. Scaled up investment in the triple pill for hypertension management in Sri Lanka should be supported to address the high population burden of cardiovascular disease.Item Hypertension – what’s in a name?(Faculty of Medicine, University of Kelaniya, Sri Lanka, 2016) Patel, A.Medical students worldwide are still taught that “hypertension” is a disease, and that if a person develops this disease, they now have a major risk factor for cardiovascular diseases (CVD). However, in countless epidemiological studies, the association between blood pressure and vascular diseases has been shown to be continuous and log-linear, and that this association persists well below traditional cut-points that have historically been used to define “hypertension”. Utilising threshold blood pressure values to define the presence or absence of a disease state is a false dichotomy that has resulted in the definition of “hypertension” being a moving target over the past 50 years. Exposing and eliminating this false dichotomy is not just an intellectual exercise or a matter of semantics. While more and more guidelines for CVD prevention adopt the “absolute risk” approach, hypertension guidelines also still persist in most countries, which is detrimental to clinical and public health approaches to CVD control. In this presentation, I will challenge the very notion of hypertension and make the case that until this term is eradicated from the medical vocabulary, huge numbers of high risk individuals will be denied treatment that has the potential to substantially impact on their disease risk. At the same time, many individuals at low risk who may have little to gain will be preferentially treated. This is particularly an issue in resource-constrained environments, where prioritising treatment for those who are likely to benefit the most is critically important. Key to addressing this issue is shifting from a paradigm of hypertension control to one of blood pressure lowering.