Safety and efficacy of rennin-angiotensin system inhibitors in heart failure with preserved ejection fraction

Background: Approximately half of the patients with chronic heart failure have preserved left ventricular systolic function. The trials of rennin-angiotensin system inhibitors (RASIs) in this population have yielded mixed results. We performed a meta-analysis of these trials to evaluate the safety and efficacy of RASIs in heart failure with preserved ejection fraction patients. Methods: A total of 8425 patients from six prospective randomized controlled trials were analyzed. The end points extracted were total mortality, cardiovascular mortality, hospitalization for heart failure, worsening of heart failure, worsening of renal failure, hyperkalemia, hypotension, six minute walk test, quality of life score. RASIs evaluated were perindopril, enalapril, ramipril, valsartan, candesartan and irbesartan. Combined odds ratios (OR) across all the studies and 95% confidence intervals (CI) were computed. A two-sided alpha error <0.05 was considered to be statistically significant. All studies were homogeneous for outcomes studied, so fixed effect model was used for this meta- analysis. Results: Both groups share similar baseline characteristics. There was significant reduction in worsening of heart failure events [OR: 1.16, CI: 1.03-1.31; p<0.05] with RASIs compared to placebo group. This was associated with a tendency toward reduced hospitalizations due to heart failure [OR: 1.11, CI: 0.99- 1.24; p=0.052] but it could not achieve statistical significance. RASIs also failed to show any benefit in total mortality [OR: 1.07, CI: 0.96-1.19; p=0.19] or cardiovascular mortality [OR: 1.01, CI: 0.89-1.15; p= 0.84] [Figure 1]. However, treatment with RASI lead to significant improvement in six minute walking distance [p<0.05] and quality of life score in RASIs group [p=0.002] [Figure 1]. Safety analysis, as expected, revealed significantly more hyperkalemic events [OR: 0.53, CI: 0.29-0.95; p<0.05] and worsening of renal failure [OR: 0.65, CI: 0.50-0.85; p<0.05] in RASI group as compared to placebo group. Conclusion: RASIs treatment in heart failure with preserve ejection fraction patients showed significant improvement in six minute walking distance, quality of life and significant reduction in worsening heart failure events but failed to reduce total and cardiovascular mortality.