Use of guideline-recommended heart failure drugs in high-, middle- and low-income countries: a systematic review and meta-analysis

Abstract

Abstract Background/Introduction Heart failure (HF)—a major health concern affecting over 64 million individuals globally—is among the leading causes of hospitalization and death, especially in low- and middle-income countries (LMICs). Guideline-directed medical therapy (GDMT) reduces the risk of hospitalization and mortality among HF patients, however previous have suggested gaps in the adoption of HF-GDMT, with very limited data from LMICs. Purpose We performed a systematic review and meta-analysis to assess the prevalence of use of GDMT for HF with mildly reduced or reduced ejection fraction and compared it across geographic regions and country income levels. Methods We searched MEDLINE, Global health, and CINAHL from inception to October 5th, 2020, for cohort and cross-sectional studies of at least 100 patients with confirmed HF and ejection fraction ≤50%. Two reviewers independently and in duplicate conducted the study selection and data extraction. The outcome was the prevalence of GDMT use, defined as the percentage of HF patients using each class of GDMT (primarily beta blockers; renin-angiotensin-system inhibitors [RASi]; mineralocorticoid receptor antagonists [MRA], diuretics). We conducted random-effects meta-analyses to obtain summary estimates for each GDMT and performed subgroup analyses at the regional and country income levels. We used meta-regression to assess the impact on study-time with prevalence of GDMT use. We assessed risk of bias using the Joanna Briggs Institute tool for analytical cross-sectional studies. Results Overall, 334 studies comprising 1,507,849 patients were included. The majority (82%) of studies were from high-income countries (HICs), followed by upper MICs (11%), lower MICs (2%) and LICs (1%). Europe (45%) and Americas regions (33%) were the most represented, Africa (1%) the least. The overall prevalence of GDMT use was high for beta blockers (80%) and RASi (82%), and relatively low for MRA (41%). There were considerable variations across income groups and geographic regions: the use of beta blockers and RASi was the highest in HICs and in the Americas, while the use of MRA were the highest in LMICs and in Europe. After adjusting for country income level, the prevalence of use was found to increase significantly by 4% for beta blockers, 2% for MRA, and 1% for RASi every year (p<0.0001). The use of diuretics (76%) and digoxin (25%) decreased with time. Few studies reported the use of newer GDMT (ivabradine, sacubitril/valsartan, vasodilators), and prevalence was found to be very low. Age, sex, or presence of hypertension or ischemic heart disease did not determine the prevalence of GDMT use. Conclusion(s) Our analyses highlight that the prevalence of use of GDMT for HF has been increasing over time, but large gaps persist, particularly in LMICs. Multi-level interventions are needed to address health-system, provider, and patient-level barriers to improve the uptake of GDMT among HF patients.