Seventy-one studies were included in the review: 57 RCTs (n=5,159) and 14 echocardiographic studies, of which 7 were cohort-controlled studies (n=5,200) and 7 were uncontrolled (n=1,279).
Only one case of valvular heart disease for an intervention participant was noted among the 41 RCTs that reported adverse effects. This was mitral regurgitation, and was judged to be due to myocardial infarction rather than drug therapy. However, echocardiography was not routinely performed in any of the RCTs.
Of the 7 cohort-controlled echocardiographic studies that evaluated the risk of valvulopathology in 5,200 obese individuals, FDA AR was found in 9.7% of those taking appetite suppressants and in 3.5% of controls. The pooled RR for FDA AR was 2.82 (95% CI: 2.20, 3.61, P<0.00001) with a NNH of 16 (95% CI: 11, 24). Data on severe aortic regurgitation was reported in 6 studies, with a pooled rate of 7 out of 3,045 (0.23%) in the exposed group, and 4 out of 1,825 (0.22%) in the control group. Following the removal of one study, to take account of the significant heterogeneity found in the analysis of FDA AR (chi-squared 16.0, P=0.01), the RR for FDA AR was 2.32 (95% CI: 1.79, 3.01, P<0.00001) with a NNH of 20 (95% CI: 13, 33).
FDA MR was much less common than FDA AR. It was found in 2.9% of those taking appetite suppressants and in 1.9% of controls. The pooled RR ratio for FDA MR was 1.55 (95% CI: 1.06, 2.25, P=0.02) with a NNH of 99 (95% CI: 44, 909). There was no evidence of significant heterogeneity.
Of the 7 uncontrolled echocardiographic surveys, a total of 236 (18%) FDA AR cases and 58 (5%) FDA MR cases were detected in the 1,279 patients evaluated. The FDA AR rates ranged from 6 to 29%. This suggested that more than 1 in 5 patients taking appetite suppressants were at risk of developing valvulopathology.