Reduced efficacy of blood pressure lowering drugs in the presence of diabetes mellitus-results from the TRIUMPH randomised controlled trial.

We 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 (ß-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.

INTEnsive care bundle with blood pressure reduction in acute cerebral hemorrhage trial (INTERACT3): study protocol for a pragmatic stepped-wedge cluster-randomized controlled trial.

BACKGROUND: Early intensive blood pressure (BP) lowering remains the most promising treatment for acute intracerebral hemorrhage (ICH), despite discordant results between clinical trials and potential variation in the treatment effects by approach to control BP. As the third in a series of clinical trials on this topic, the INTEnsive care bundle with blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT3) aims to determine the effectiveness of a goal-directed care bundle protocol of early physiological control (intensive BP lowering, glycemic control, and pyrexia treatment) and reversal of anticoagulation, in acute ICH. METHODS: INTERACT3 is a pragmatic, international, multicenter, stepped-wedge (4 phases/3 steps), cluster-randomized controlled trial to determine the effectiveness of a multifaceted care package in adult (age ≥ 18 years) patients (target 8360) with acute ICH (< 6 h of onset) recruited from 110 hospitals (average of 19 consecutive patients per phase) in low- and middle-income countries. After a control phase, each hospital implements the intervention (intensive BP lowering, target systolic < 140 mmHg; glucose control, target 6.1-7.8 mmol/L and 7.8-10.0 mmol/L in those without and with diabetes mellitus, respectively; anti-pyrexia treatment to target body temperature ≤ 37.5 °C; and reversal of anticoagulation, target international normalized ratio < 1.5 within 1 h). Information will be obtained on demographic and baseline clinical characteristics, in-hospital management, and 7-day outcomes. Central trained blinded assessors will conduct telephone interviews to assess physical function and health-related quality of life at 6 months. The primary outcome is the modified Rankin scale (mRS) at 6 months analyzed using ordinal logistic regression. The sample size of 8360 subjects provides 90% power (α = 0.05) to detect a 5.6% absolute improvement (shift) in the primary outcome of the intervention versus control standard care, with various assumptions. DISCUSSION: As the largest clinical trial in acute ICH, INTERACT3 is on schedule to provide an assessment of the effectiveness of a widely applicable goal-directed care bundle for a serious condition in which a clearly proven treatment has yet to be established. TRIAL REGISTRATION: ClinicalTrials.gov NCT03209258. Registered on 1 July 2017. Chinese Trial Registry ChiCTR-IOC-17011787. Registered on 28 June 2017.

Control of blood pressure and risk attenuation: a public health intervention in rural Bangladesh, Pakistan, and Sri Lanka: feasibility trial results.

BACKGROUND: High blood pressure (BP) is the leading attributable risk for cardiovascular disease globally. There is little information on effective and sustainable public health system strategies for managing hypertension in South Asian countries. We conducted a feasibility study to gather preliminary data to optimize BP-lowering strategies for a public health intervention in rural communities in Bangladesh, Pakistan, and Sri Lanka. METHODS: A mixed method feasibility study comprised a 3-month pre and postevaluation of a multicomponent intervention (MCI), including BP screening and home health education by trained government community health worker (CHW); providers trained in hypertension management, and compensation of CHW for additional services. Checklists were used to document care. Stakeholder interviews were also conducted. Individuals aged 40 years and above with high BP (systolic ≥140 mmHg or diastolic ≥90 mmHg based on two readings from 2 separate days, or receiving antihypertensive medications) were enrolled from rural communities in Bangladesh, Pakistan, and Sri Lanka. BP was measured at baseline and 3 months postintervention. RESULTS: A total of 412 (90%) of the 454 eligible individuals were recruited. Of those recruited, 90% received home health education session by trained CHWs, 80% were referred to trained providers, of whom 83% completed the management checklist. A follow-up rate of 95.6% was achieved. The mean SBP declined significantly by 4.5 mmHg 95% confidence interval (2.3, 6.7) mmHg (P < 0.001) in the overall pooled analysis in three countries; however, it varied among countries. BP decline was 10.5 mmHg (8.1, 13.0 mmHg) (P < 0.001) in the pooled analysis of individuals with uncontrolled hypertension at baseline, and was also significant each of the three countries. All 98 stakeholders strongly supported upscaling the proposed MCI strategies. CONCLUSION: The proposed MCI is feasible for implementation and requires long-term, large-scale evaluation in the rural public health infrastructure in South Asian countries to determine sustainability of health system changes and BP control. If these long-term effects are confirmed, MCI may be a long-term strategy for tackling rising rates of cardiovascular disease in low-resourced countries.Clintrial.gov NCT02341651.