Use of Guideline-Recommended Heart Failure Drugs in High-, Middle-, and Low-Income Countries: A Systematic Review and Meta-Analysis.

Optimal use of guideline-directed medical therapy (GDMT) can prevent hospitalization and mortality among patients with heart failure (HF). We aimed to assess the prevalence of GDMT use for HF across geographic regions and country-income levels. We systematically reviewed observational studies (published between January 2010 and October 2020) involving patients with HF with reduced ejection fraction. We conducted random-effects meta-analyses to obtain summary estimates. We included 334 studies comprising 1,507,849 patients (31% female). The majority (82%) of studies were from high-income countries, with Europe (45%) and the Americas (33%) being the most represented regions, and Africa (1%) being the least. Overall prevalence of GDMT use was 80% (95% CI 78%-81%) for ß-blockers, 82% (80%-83%) for renin-angiotensin-system inhibitors, and 41% (39%-43%) for mineralocorticoid receptor antagonists. We observed an exponential increase in GDMT use over time after adjusting for country-income levels (p < 0.0001), but significant gaps persist in low- and middle-income countries. Multi-level interventions are needed to address health-system, provider, and patient-level barriers to GDMT use.

Low-Dose Triple-Pill vs Standard-Care Protocols for Hypertension Treatment in Nigeria: A Randomized Clinical Trial.

Importance: With the high burden of hypertension in sub-Saharan Africa, there is a need for effective, safe and scalable treatment strategies. Objective: To compare, among Black African adults, the effectiveness and safety of a novel low-dose triple-pill protocol compared with a standard-care protocol for blood pressure lowering. Design and Setting: Randomized, parallel-group, open-label, multicenter trial conducted in public hospital-based family medicine clinics in Nigeria. Participants: Black African adults with uncontrolled hypertension (≥140/90 mm Hg) who were untreated or receiving a single blood pressure-lowering drug. Interventions: Participants were randomly allocated to low-dose triple-pill or standard-care protocols. The triple-pill protocol involved a novel combination of telmisartan, amlodipine, and indapamide in triple one-quarter, one-half, and standard doses (ie, 10/1.25/0.625 mg, 20/2.5/1.25 mg, and 40/5/2.5 mg), with accelerated up-titration. The standard-care protocol was the Nigeria hypertension treatment protocol starting with amlodipine (5 mg). Main Outcomes and Measures: The primary effectiveness outcome was the reduction in home mean systolic blood pressure, and the primary safety outcome was discontinuation of trial treatment due to adverse events, both from randomization to month 6. Results: The first participant was randomized on July 19, 2022, and the last follow-up visit was on July 18, 2024. Among 300 randomized participants (54% female; mean age, 52 years; baseline mean home blood pressure, 151/97 mm Hg; and clinic blood pressure, 156/97 mm Hg), 273 (91%) completed the trial. At month 6, mean home systolic blood pressure was on average 31 mm Hg (95% CI, 28 to 33 mm Hg) lower in the triple-pill protocol group and 26 mm Hg (95% CI, 22 to 28 mm Hg) lower in the standard-care protocol group (adjusted difference, -5.8 mm Hg [95% CI, -8.0 to -3.6]; P < .001]). At month 6, clinic blood pressure control (<140/90 mm Hg) was 82% vs 72% (risk difference, 10% [95% CI, -2% to 20%]) and home blood pressure control (<130/80 mm Hg) was 62% vs 28% (risk difference, 33% [95% CI, 22% to 44%]) in the triple-pill compared with the standard-care protocol group; these were 2 of 21 prespecified secondary effectiveness end points. No participants discontinued trial treatment due to adverse events. Conclusions and Relevance: Among Black African adults with uncontrolled hypertension, a low-dose triple-pill protocol achieved better blood pressure lowering and control with good tolerability compared with the standard-care protocol. Trial Registration: Pan African Clinical Trials Registry Identifier: PACTR202107579572114.

deliVERy of optimal blood pressure coNtrol in afrICA (VERONICA)-Nigeria study: Rationale and design of a randomized clinical trial.

BACKGROUND: Blood pressure (BP) control among treated patients in Africa is very suboptimal, with low levels of combination therapy use and therapeutic inertia being among the major barriers to effective control of hypertension. The VERONICA-Nigeria study aims to evaluate, among Black African adults with hypertension, the effectiveness and safety of a triple pill-based treatment protocol compared to Nigeria hypertension treatment protocol (standard care protocol) for the treatment of hypertension. METHODS: This study involves a randomized, parallel-group and open-label trial. Adults with uncontrolled hypertension (n = 300), untreated or receiving monotherapy, with no contraindication to study treatments will be randomly assigned 1:1 to treatment with a triple pill based-treatment protocol or standard care protocol. Follow-up is for 6 months, with interim follow up visits at month 1, 2, and 3. In a noncomparative extension treatment period, participants completing the 6 months randomized period and on ≤3 BP-lowering drugs will receive treatment with the triple pill-based treatment protocol for 12 months. The primary outcome is change in home mean SBP from baseline to month 6, and key secondary efficacy outcome is percentage of participants with clinic BP <140/90 mmHg at month 6. The primary safety outcome is discontinuation of trial treatment due to adverse events from randomization to month 6. Economic evaluation will be conducted to assess the cost-effectiveness of the triple pill-based treatment protocol, and process evaluation will be conducted to understand the context in which the trial was conducted, implementation of the trial and interventions and mechanisms of effect, and potential barriers and facilitators to implementing the intervention in clinical practice. CONCLUSION: The VERONICA-Nigeria trial will provide evidence of effectiveness and safety of the triple-based treatment protocol for the pharmacological management of hypertension, in Black African adults. TRIAL REGISTRATION: PACTR202107579572114.

Comparison of Indian clinical practice guidelines for the management of hypertension with the World Health Organization, International Society of Hypertension, American, and European guidelines.

Hypertension is the leading risk factor for preventable cardiovascular diseases and all-cause mortality globally, with majority of the hypertension-attributed deaths occurring in low- and middle-income countries like India. Several international and national clinical practice guidelines (CPGs) provide evidence-informed recommendations to achieve optimal control. CPGs produced by the World Health Organization, International Society for Hypertension, American (AHA/ACC-2017), and European (ESC/ESH-2018) are "major" as they are widely used and are highly cited. We compared the main recommendations for the pharmacological management of hypertension among the major CPGs and the two existing Indian CPGs for similarities and shortcomings. Several deviations from the major CPGs were observed among Indian CPGs. Important shortcomings pertain to Indian CPGs' low priority for initial combination therapy and the use of single pill combinations. Having multiple CPGs providing conflicting recommendations might discourage the adoption of evidence-based practices. There is a need for updating Indian CPGs based on up-to-date evidence.

Standardized treatment protocols for hypertension: global availability, characteristics, and alignment with the hypertension guideline recommendations.

BACKGROUND: Hypertension control is suboptimal globally. Implementing evidence-based, simple, standardized treatment protocols (STPs) has been instrumental in effectively and efficiently improving treatment and control of hypertension. We aimed to identify, characterize, and critically appraise hypertension STPs. METHODS: We defined STP as a series of steps for the pharmacological treatment of primary hypertension, with information on target population, BP threshold for treatment initiation, target BP, specific drugs/classes/doses, and follow-up frequency. STPs for adult patients were identified from the websites of relevant health organizations, Google search, and through expert consultations (until July 2023). STPs for secondary, gestational, or malignant hypertension or those that were templates/samples were excluded. Included STPs were critically appraised using HEARTS in the Americas Checklist for hypertension management in primary care and compared with the 2021 WHO hypertension management guideline recommendations. RESULTS: Fifty STPs were identified. All STPs had a stepwise treatment approach, involved guideline-recommended first-line drugs, and 98% consisted of at least four steps. Majority (54%) recommended monotherapy with calcium channel blockers as first-line treatment. Only 44% STPs recommended treatment initiation with combination therapy, and 16% recommended single-pill combinations. Most (62%) had dose-intensification as the second step. Most (74%) STPs did not provide complete dosing information. Only one STP mentioned a target time for achieving BP control. On average, STPs scored a performance of 68% on the HEARTS Checklist. CONCLUSION: Several STPs are available globally; however, most of them have enormous scope for improvement through interventions aimed at alignment with the latest evidence-based guidelines and multistakeholder engagement.

Quality of the Indian clinical practice guidelines for the management of cardiovascular conditions.

To assess the quality of Indian clinical practice guidelines (CPG)s for the management of cardiovascular conditions, MEDLINE, Embase, Google Scholar and websites of relevant medical associations and government organisations were searched, from inception until August 2020, to identify Indian CPGs for the management of cardiovascular disease (CVD) conditions, produced in or between 2010 and 2019. Excluded were CPGs that were not specific to India, focused on alternative systems of medicine, of non-CVD conditions (even if they included a component of CVD), and those related to the electronic devices, cardiac biomarkers, or diagnostic procedures. Quality of the each included CPG was assessed using the AGREE II tool by four reviewers in duplicate, independently. Each AGREE II domain score and overall quality score was considered low (≤40%), moderate (40.1%-59.9%), and high (≥60%). Of the 23 CPGs included, six (26%) were reported to be adapted from other CPGs. Fourteen (61%) CPGs were produced by medical associations, six (26%) by individual authors and three (13%) by government agencies. Based on the AGREE II overall quality score, two (9%) CPGs were of high quality, four (17%) and seventeen (74%) CPGs were of moderate and low quality, respectively. Except for scope and purpose, and clarity of presentation all other domains were rated low. The quality of most Indian CPGs for managing CVD conditions assessed using the AGREE II tool was moderate-to-low. Combined efforts from different stakeholders are needed to develop, disseminate and implement high-quality CPGs while identifying and addressing barriers to their uptake to optimize patient care and improve outcomes.

Quality of systematic reviews supporting the 2017 ACC/AHA and 2018 ESC/ESH guidelines for the management of hypertension.

OBJECTIVE: To assess the methodological and reporting quality of systematic reviews (SRs) that informed recommendations in the recent American and European hypertension guidelines. DESIGN AND SETTINGS: Meta-epidemiological study. We identified SRs that were cited for class I recommendations based on Level of Evidence-A in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) and the 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) hypertension guidelines. MAIN OUTCOME MEASURES: Methodological and reporting quality of the SRs was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR-2) checklist and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, respectively. RESULTS: A total of 40 SRs was included in the analysis (28 from 2017 ACC/AHA; 22 from 2018 ESC/ESH and 10 were included in both). Based on the AMSTAR-2 assessment, only 7.5% SRs were found to be of high methodological quality, 47.5% were of moderate, each 22.5% were of low and critically low quality. Based on the PRISMA checklist assessment, a mean of 24 items (SD (2.76) were reported appropriately, and only five SRs reported all 27 items appropriately. CONCLUSION: Methodological and reporting quality of SRs were found to vary considerably. Lack of information on the funding source of included studies, use of a protocol, integration of risk of bias assessments while interpreting findings and reporting of excluded studies were major methodological deficiencies.

Systematic reviews of antihypertensive drugs: A review of publication trends, characteristics, and quality.

This review presents publication trends, characteristics, and quality of systematic reviews (SRs) of randomized controlled trials (RCTs) of antihypertensive drugs (AHTDs). Between 1985 and 2017, 1,173 SRs were published, and in the last 20 years, 10, 35, and 116 were published in the year 1996, 2006, and 2016, respectively. Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers were the most common class of drugs studied. Fourteen percent of the SRs were prospectively registered/published protocol. Three-fourth of the SRs did not report a full search strategy, and 45% did not report a PRISMA or similar diagram. Of the 34 SRs published in the five high impact factor journals in the last 10 years, 15%, 21%, and 65% have unclear, low, and high risk of bias, respectively. There has been a steady increase in the publication of SRs of RCTs of AHTDs. However, adherence to standard methods of conduct and reporting continues to be low.