A cardiovascular polypill for secondary stroke prevention in a tertiary centre in Ghana (SMAART): a phase 2 randomised clinical trial.

BACKGROUND: A cardiovascular polypill containing generic drugs might facilitate sustained implementation of and adherence to evidence-based treatments, especially in resource-limited settings. However, the impact of a cardiovascular polypill in mitigating atherosclerotic risk among stroke survivors has not been assessed. We aimed to compare a polypill regimen with usual care on carotid intima-media thickness (CIMT) regression after ischaemic stroke. METHODS: In SMAART, a phase 2 parallel, open-label, assessor-masked, randomised clinical trial, we randomly allocated individuals (aged ≥18 years) who had an ischaemic stroke within the previous 2 months, using a computer-generated randomisation sequence (1:1), to either a polypill or usual care group at a tertiary centre in Ghana. The polypill regimen was a fixed-dose pill containing 5 mg ramipril, 50 mg atenolol, 12·5 mg hydrochlorothiazide, 20 mg simvastatin, and 100 mg aspirin administered as two capsules once per day for 12 months. Usual care was tailored guideline-recommended secondary prevention medications. The primary outcome was the change in CIMT over 12 months with adjustment for baseline values, compared using ANCOVA in all participants with complete data at month 12. Safety was analysed in all randomly assigned participants. This trial is registered at ClinicalTrials.gov, NCT03329599, and is completed. FINDINGS: Between Feb 12, 2019, and Dec 4, 2020, we randomly assigned 148 participants (74 to the usual care group and 74 to the polypill group), 74 (50%) of whom were male and 74 (50%) female. CIMT was assessed in 62 (84%) of 74 participants in the usual care group and 59 (80%) of 74 participants in the polypill group; the main reason for loss to follow-up was participants not completing the study. The mean CIMT change at month 12 was -0·092 mm (95% CI -0·130 to -0·051) in the usual care group versus -0·017 mm (-0·067 to 0·034) in the polypill group, with an adjusted mean difference of 0·049 (-0·008 to 0·109; p=0·11). Serious adverse events occurred among two (3%) participants in the usual care group, and eight (11%) participants in the polypill group (p=0·049). INTERPRETATION: The polypill regimen resulted in similar regression in subclinical atherosclerosis and many secondary and tertiary outcome measures as the tailored drug regimen, but with more serious adverse events. Larger, longer-term, event-based studies, including patients with stroke in primary care settings, are warranted. FUNDING: US National Institutes of Health. TRANSLATION: For the Akan (Twi) translation of the abstract see Supplementary Materials section.

Clinical and laboratory profile and outcomes of hospitalized COVID-19 patients with type 2 diabetes mellitus in Ghana - A single-center study.

BACKGROUND: In sub-Saharan Africa and particularly in Ghana, there is scarcity of published literature specifically on the impact of DM on outcomes in COVID-19 patients. Based on the difference in genetic makeup and demographic patterns in Africans compared to the Western world and with the rising burden of DM and other non-communicable diseases in Ghana there is a need to define the impact DM has on persons with COVID-19. This would ensure adequate risk stratification and surveillance for such patients as well as appropriate scale up of therapeutic management if needed. AIMS: This single-center study describes the clinical and laboratory profile and outcomes of COVID-19 in-patients with type 2 diabetes mellitus (DM) in Ghana. MATERIALS AND METHODS: Retrospective analysis was undertaken of the medical records of adults with COVID-19 hospitalized at a facility in Ghana from March to October 2020. Clinical, laboratory and radiological data and outcomes were analysed. Comparisons between COVID-19 patients with DM and non-diabetics were done with an independent t-test or a Mann-Whitney test when normality was not attained. Odds ratios (95% CI) were calculated using univariate logistic regression. RESULTS: Out of 175 COVID-19 patients, 64 (36.6%) had DM. Overall mean age was 55.9 ± 18.3 years; DM patients were older compared to non-diabetics (61.1 ± 12.8 vs. 53.0 ± 20.2 years, p = .049). Compared to non-diabetics, diabetics were more likely to have higher blood glucose at presentation, have hypertension, be on angiotensin 2 receptor blockers [OR, 95% CI 3.3 (1.6-6.7)] and angiotensin converting enzyme inhibitors [OR, 95% CI 3.1 (1.3-7.4)]; and be HIV negative (p < .05). Although the values were normal, diabetics had a higher platelet count but decreased lymphocytes, aspartate transaminase and alkaline phosphatase compared to non-diabetics (p < .05). There was no difference in clinical symptoms, severity or mortality between the two groups. DISCUSSION: The clinical profile of patients studied are similar to prior studies. However the outcome of this study showed that DM was not associated with worse clinical severity and in-hospital mortality. This could have been due to majority of DM patients in this study having relatively good blood glucose control on admission. Secondly, DM alone may not be a risk factor for mortality. Rather its concurrent existence with multiple co-morbidities (especially cardiovascular co-morbidities which may predispose to pro-inflammatory and pro-thrombotic states) may be driving the rise in severity and mortality risks reported in other studies. Furthermore, this study was conducted among an African population and Africa has been shown to be generally less severely hit by the COVID-19 pandemic compared to other regions outside the continent. This has been postulated to be due, among other factors, to inherent protective mechanisms in Africans due to early and repeated exposure to parasitic and other organisms resulting in a robust innate immunity. CONCLUSIONS: This study suggested that DM was not associated with more severe clinical symptoms or worse outcomes among hospitalized COVID-19 patients. Despite this, it is important that DM patients adhere to their therapy, observe the COVID-19 containment protocols and are prioritized in the administration of the COVID-19 vaccines. STUDY HIGHLIGHTS: In this retrospective, single-centre study on the clinical and laboratory profile and outcome of hospitalized DM patients with COVID-19, patients with DM did not have a more severe clinical profile or worse outcomes. They were, however, significantly older, more likely to have higher admission blood glucose, have hypertension, be on angiotensin 2 receptor blockers and angiotensin converting enzyme inhibitors; and be HIV negative compared to the cohort without DM. DM patients should be a priority group for the COVID-19 vaccines.