Table 1.
Randomized Clinical Trials of Losartan in Marfan Syndrome*
| Trial Name | Trial Type | Drugs Tested | Dose Range | No. Enrolled | Enroll Age, y | Follow-Up, y | Primary Outcome | Results | Notes |
|---|---|---|---|---|---|---|---|---|---|
| Pediatric Heart Network28,29 | Double blind, stratified | Atenolol | 0.5–4.0 mg/kg per d | 608 | 0.5–25 | 3.0±0.1 | Rate of change in root Z score per year | Not significant (P=0.08) | FBN1 sequencing and pharmacogenomics studies pending |
| Losartan | 0.4–1.4 mg/kg per d | ||||||||
| COMPARE33 | Open label | Losartan | 50 or 100 mg/d | 233 | >18 | 3.1±0.4 | Change in absolute root diameter | P=0.014 | Significant only in individuals with FBN1 haploinsufficiency mutations |
| No additional drug | |||||||||
| Spanish31 | Double blind | Atenolol | 25–100 mg/d | 140 | 5–60 | 3.0 | Change in absolute diameter or Z score of root and ascending aorta | Not significant (P=0.193) | Ambulatory blood pressures were not different between groups |
| Losartan | 25–100 mg/d | ||||||||
| Marfan Sartan30 | Double blind | Losartan | 50 or 100 mg/d | 299 | >10 | 3.5 | Rate of change in root Z score per year | Not significant (P=0.36) | 100% sequenced and 78% had FBN1 mutations |
| Placebo | |||||||||
| Taiwanese34 | Open label | Losartan+BB | Losartan: 25–100 mg/d or 0.7 mg/kg per d to 50 mg/d | 29 | P=0.02 | ||||
| BB: 50 mg atenolol/20 mg propranolol or 1 mg/kg per d | |||||||||
| BB | Any dose <150 mg/d or <2 mg/kg/d | ||||||||
| Placebo | |||||||||
| Ghent Marfan Trial35 | Double blind, stratified | Losartan+BB | Losartan: 50 or 100 mg/d | 22 | >10 | 3 | Rate of change in absolute root diameter or Z score per year | Not significant | |
| Placebo+BB | mg/d BB: NA |
BB indicates β-blocker; COMPARE, Cozaar in Marfan Patients Reduces Aortic Enlargement; and NA, not available.
*
All studies included the modified Ghent criteria as an inclusion criterion.