Rationale and design of the Newer Versus Older Antihypertensive Agents in African Hypertensive Patients (NOAAH) trial

Abstract Background. Sub-Saharan Africa experiences an epidemic surge in hypertension. Studies in African Americans led to the recommendation to initiate antihypertensive treatment in Blacks with a diuretic or a low-dose fixed combination including a diuretic. We mounted the Newer versus Older Antihypertensive Agents in African Hypertensive Patients (NOAAH) trial to compare in native African patients a fixed combination of newer drugs, not involving a diuretic, with a combination of older drugs including a diuretic. Methods. Patients aged 30-69 years with uncomplicated hypertension (140-179/90-109 mmHg) and two or fewer associated risk factors are eligible. After a 4-week run-in period off treatment, 180 patients will be randomized to once daily bisoprolol/hydrochlorothiazide 5/6.25 mg or amlodipine/valsartan 5/160 mg. To attain and maintain blood pressure below 140/90 mmHg during 6 months of follow-up, the doses of bisoprolol and amlodipine in the combination tablets will be increased to 10 mg/day with the possible addition of α-methyldopa or hydralazine. NOAAH is powered to demonstrate a 5-mmHg between-group difference in sitting systolic pressure with a two-sided p-value of 0.01 and 90% power. NOAAH is investigator-led and complies with the Helsinki declaration. Results. Six centers in four sub-Saharan countries started patient recruitment on September 1, 2010. On December 1, 195 patients were screened, 171 were enrolled, and 51 were randomized and followed up. The trial will be completed in the third quarter of 2011. Conclusions. NOAAH (NCT01030458) is the first randomized multicenter trial of antihypertensive medications in hypertensive patients born and living in sub-Saharan Africa.status: publishe

Progress report on the first sub-Saharan Africa trial of newer versus older antihypertensive drugs in native black patients

BACKGROUND: The epidemic surge in hypertension in sub-Saharan Africa is not matched by clinical trials of antihypertensive agents in Black patients recruited in this area of the world. We mounted the Newer versus Older Antihypertensive agents in African Hypertensive patients (NOAAH) trial to compare, in native African patients, a single-pill combination of newer drugs, not involving a diuretic, with a combination of older drugs including a diuretic. METHODS: Patients aged 30 to 69 years with uncomplicated hypertension (140 to 179/90 to 109 mmHg) and ≤2 associated risk factors are eligible. After a four week run-in period off treatment, 180 patients have to be randomized to once daily bisoprolol/hydrochlorothiazide 5/6.25 mg (R) or amlodipine/valsartan 5/160 mg (E). To attain blood pressure <140/<90 mmHg during six months, the doses of bisoprolol and amlodipine should be increased to 10 mg/day with the possible addition of up to 2 g/day α-methyldopa. RESULTS: At the time of writing of this progress report, of 206 patients enrolled in the run-in period, 140 had been randomized. At randomization, the R and E groups were similar (P ≥ 0.11) with respect to mean age (50.7 years), body mass index (28.2 kg/m(2)), blood pressure (153.9/91.5 mmHg) and the proportions of women (53.6%) and treatment naïve patients (72.7%). After randomization, in the R and E groups combined, blood pressure dropped by 18.2/10.1 mmHg, 19.4/11.2 mmHg, 22.4/12.2 mmHg and 25.8/15.2 mmHg at weeks two (n = 122), four (n = 109), eight (n = 57), and 12 (n = 49), respectively. The control rate was >65% already at two weeks. At 12 weeks, 12 patients (24.5%) had progressed to the higher dose of R or E and/or had α-methyldopa added. Cohort analyses of 49 patients up to 12 weeks were confirmatory. Only two patients dropped out of the study. CONCLUSIONS: NOAAH (NCT01030458) demonstrated that blood pressure control can be achieved fast in Black patients born and living in Africa with a simple regimen consisting of a single-pill combination of two antihypertensive agents. NOAAH proves that randomized clinical trials of cardiovascular drugs in the indigenous populations of sub-Saharan Africa are feasible

Progress report on the first sub-Saharan trial of newer versus older antihypertensive drugs in native black patients

ABSTRACT: BACKGROUND: The epidemic surge in hypertension in sub-Saharan Africa is not matched by clinical trials of antihypertensive agents in Black patients recruited in this area of the world. We mounted the Newer versus Older Antihypertensive agents in African Hypertensive patients (NOAAH) trial to compare, in native African patients, a single-pill combination of newer drugs, not involving a diuretic, with a combination of older drugs including a diuretic. METHODS: Patients aged 30 to 69 years with uncomplicated hypertension (140 to 179/90 to 109 mmHg) and [less than or equal to]2 associated risk factors are eligible. After a four week run-in period off treatment, 180 patients have to be randomized to once daily bisoprolol/hydrochlorothiazide 5/6.25 mg (R) or amlodipine/valsartan 5/160 mg (E). To attain blood pressure 65% already at two weeks. At 12 weeks, 12 patients (24.5%) had progressed to the higher dose of R or E and/or had alpha-methyldopa added. Cohort analyses of 49 patients up to 12 weeks were confirmatory. Only two patients dropped out of the study. CONCLUSIONS: NOAAH (NCT01030458) demonstrated that blood pressure control can be achieved fast in Black patients born and living in Africa with a simple regimen consisting of a single-pill combination of two antihypertensive agents. NOAAH proves that randomized clinical trials of cardiovascular drugs in the indigenous populations of sub-Saharan Africa are feasible.status: publishe

Heart rate variability on antihypertensive drugs in black patients living in sub-Saharan Africa

BACKGROUND: Compared with Caucasians, African Americans have lower heart rate variability (HRV) in the high-frequency domain, but there are no studies in blacks born and living in Africa. METHODS: In the Newer versus Older Antihypertensive agents in African Hypertensive patients trial (NCT01030458), patients (30–69 years) with uncomplicated hypertension (140–179/90–109 mmHg) were randomized to single-pill combinations of bisoprolol/hydrochlorothiazide (R) or amlodipine/valsartan (E). 72 R and 84 E patients underwent 5-min ECG recordings at randomization and 8, 16 and 24 weeks. HRV was determined by fast Fourier transform and autoregressive modelling. RESULTS: Heart rate decreased by 9.5 beats/min in R patients with no change in E patients (− 2.2 beats/min). R patients had reduced total (− 0.13 ms²; p = 0.0038) and low-frequency power (− 3.6 nu; p = 0.057), higher high-frequency (+ 3.3 nu; p = 0.050) and a reduced low- to high-frequency ratio (− 0.08; p = 0.040). With adjustment for heart rate, these differences disappeared, except for the reduced low-frequency power in the R group (− 4.67 nu; p = 0.02). Analyses confined to 39 R and 47 E patients with HRV measurements at all visits or based on autoregressive modelling were confirmatory. CONCLUSION: In native black African patients, antihypertensive drugs modulate HRV, an index of autonomous nervous tone. However, these effects were mediated by changes in heart rate except for low-frequency variability, which was reduced on beta blockade independent of heart rate

Heart rate variability on antihypertensive drugs in Black patients living in sub-Saharan Africa

Background. Compared with Caucasians, African Americans have lower heart rate variability (HRV) in the high-frequency domain, but there are no studies in Blacks born and living in Africa. Methods. In the Newer versus Older Antihypertensive agents in African Hypertensive patients trial (NCT01030458), patients (30-69 years) with uncomplicated hypertension (140-179/90-109 mmHg) were randomized to single-pill combinations of bisoprolol/hydrochlorothiazide (R) or amlodipine/valsartan (E). 72 R and 84 E patients underwent 5-min ECG recordings at randomization and 8, 16 and 24 weeks. HRV was determined by fast Fourier transform and autoregressive modelling. Results. Heart rate decreased by 9.5 beats/min in R patients with no change in E patients (- 2.2 beats/min). R patients had reduced total (- 0.13 ms²; p = 0.0038) and low-frequency power (- 3.6 nu; p = 0.057), higher high-frequency (+ 3.3 nu; p = 0.050) and a reduced low- to high-frequency ratio (- 0.08; p = 0.040). With adjustment for heart rate, these differences disappeared, except for the reduced low-frequency power in the R group (- 4.67 nu; p = 0.02). Analyses confined to 39 R and 47 E patients with HRV measurements at all visits or based on autoregressive modelling were confirmatory. Conclusion. In native Black African patients, antihypertensive drugs modulate HRV, an index of autonomous nervous tone. However, these effects were mediated by changes in heart rate except for low-frequency variability, which was reduced on beta blockade independent of heart rate.peerreview_statement: The publishing and review policy for this title is described in its Aims & Scope. aims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=iblo20status: publishe

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit