Acute heart failure (AHF) is frequent and life-threatening disease. However, innovative AHF therapies have remained limited, and care is based on experts' opinion. Temporal trends and benefits of long-term oral cardiovascular medications on AHF outcomes remain uncertain. This study is registered with PROSPERO (CRD42018099885). A systematic review ranging from 1980 to 2017, searched AHF studies with more than 100 patients that reported death and/or readmission. Primary outcomes were temporal trends, assessed by meta-regression, for 30-day or 1-year all-cause death and/or readmission rates. Secondary outcomes were temporal trends of oral cardiovascular therapies and their influence on primary outcomes. Among the 45 143 studies screened, 285 were included, representing 15 million AHFs. In the past decades, though mortality and readmission remain high, there was a decline in 30-day all-cause death [odds ratio (OR) for a 10-year increment: 0.74, 95% confidence interval (CI) 0.61-0.91; P=0.004] that persisted at 1 year (OR 0.86, 95% CI 0.77-0.96; P=0.007), while 30-day and 1-year all-cause readmission rate remained roughly unchanged. Trends of primary outcomes were linear and did not differ among continents. Decline in 1-year all-cause death rate correlated with high proportions of oral or beta-blockers, especially when combined with oral renin-angiotensin-aldosterone system inhibitors, but not with diuretics while trends in readmission remained unchanged with these therapies. Although AHF outcomes remain poor, the present study revealed global favourable trends of survival after AHF episodes probably associated with greater use of oral neurohormonal antagonists. The present study urges to implement the combination of oral renin-angiotensin-aldosterone system inhibitors and beta-blockers in patients at risk of AHF.