Aldosterone Blockade in Acute Myocardial Infarction: A Systematic Review and Meta-Analysis

Background. A comprehensive evaluation of the benefits of mineralocorticoid receptor antagonists (MRA) in acute myocardial infarction (AMI) patients is lacking. Objective. To summarize the evidence on the efficacy and safety of MRA in patients admitted for AMI. Methods. Articles were identified through PubMed, Embase, Cochrane Library, Ovid (Medline1946-2021), and ClinicalTrials.gov databases from their inception to December 31, 2020. Results. 15 articles with a total of 11,861 patients were included. MRA reduced the risk of all-cause mortality by 16% (relative ratio (RR): 0.84; 95% confidence interval (CI) (0.76, 0.94); <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mi>P</a:mi> <a:mo>=</a:mo> <a:mn>0.002</a:mn> </a:math> ) and the incidence of cardiovascular adverse events by 12% (RR: 0.88, 95% CI (0.83, 0.93), <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mi>P</c:mi> <c:mo><</c:mo> <c:mn>0.00001</c:mn> </c:math> ) in post-AMI patients, and further analysis demonstrated that early administration of MRA within 7 days after AMI resulted in a greater reduction in all-cause mortality (RR: 0.72, 95% CI (0.61, 0.85), <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"> <e:mi>P</e:mi> <e:mo><</e:mo> <e:mn>0.0001</e:mn> </e:math> ). Subgroup analyses showed that post-STEMI patients without left ventricular systolic dysfunction (LVSD) treated with MRA had a 36% reduction in all-cause mortality (RR: 0.64, 95% CI (0.46, 0.89), <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" id="M4"> <g:mi>P</g:mi> <g:mo>=</g:mo> <g:mn>0.007</g:mn> </g:math> ) and a 22% reduction in cardiovascular adverse events (RR: 0.78, 95% CI (0.67, 0.91), <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" id="M5"> <i:mi>P</i:mi> <i:mo>=</i:mo> <i:mn>0.002</i:mn> </i:math> ). Meanwhile, post-STEMI patients without LVSD treated with MRA get significant improvements in left ventricular ejection fraction (mean difference (MD): 2.69, 95% CI (2.44, 2.93), <k:math xmlns:k="http://www.w3.org/1998/Math/MathML" id="M6"> <k:mi>P</k:mi> <k:mo><</k:mo> <k:mn>0.00001</k:mn> </k:math> ), left ventricular end-systolic index (MD: -4.52 ml/m2, 95% CI (-8.21, -0.83), <m:math xmlns:m="http://www.w3.org/1998/Math/MathML" id="M7"> <m:mi>P</m:mi> <m:mo>=</m:mo> <m:mn>0.02</m:mn> </m:math> ), and left ventricular end-diastolic diameter (MD: -0.11 cm, 95% CI (-0.22, 0.00), <o:math xmlns:o="http://www.w3.org/1998/Math/MathML" id="M8"> <o:mi>P</o:mi> <o:mo>=</o:mo> <o:mn>0.05</o:mn> </o:math> ). The corresponding RR were 1.72 (95% CI (1.43, 2.07), <q:math xmlns:q="http://www.w3.org/1998/Math/MathML" id="M9"> <q:mi>P</q:mi> <q:mo><</q:mo> <q:mn>0.00001</q:mn> </q:math> ) for considered common adverse events (hyperkalemia, gynecomastia, and renal dysfunction). Conclusions. Our findings suggest that MRA treatment reduces all-cause mortality and cardiovascular adverse events in post-AMI patients, which is more significant in patients after STEMI without LVSD. In addition, MRA treatment may exert beneficial effects on the reversal of cardiac remodeling in patients after STEMI without LVSD.