Cardiovascular outcomes in hypertensive patients who discontinue study medication in a large outcome trial. the life study.

Objective: Patient discontinuation of study medication during a hypertension outcome trial has implications for study power. We aimed to assess patient characteristics and outcomes in patients with hypertension and left ventricular hypertrophy (LVH) who discontinued the study drug but otherwise remained in the study until the end of follow-up. Methods: In patients who discontinued vs. those continuing, Cox proportional hazards models identified baseline variables that had a significant impact on the occurrence of the primary composite endpoint (cardiovascular death, stroke, and myocardial infarction) in 9,193 hypertensive patients and LVH in the LIFE study. Results: During a mean follow-up of 4.8 years, 3,281 patients (35.7%) discontinued one or more days, not counting death as a reason for discontinuation. The distribution of days to discontinuation was highly skewed towards the first part of the study; the 25 th percentile was at day 161, and the median was at day 669. Reasons for discontinuation were a clinical adverse event (50%), a secondary study endpoint (19%), required study therapy (11%), withdrawal (2%), administrative (18%), and lost to follow-up (0.2%). Those who discontinued were older, more often male, had slightly lower body mass index, higher systolic and lower diastolic pressure, higher Framingham Risk Score (FRS), and more ECG LVH determined by either Cornell product or Sokolow-Lyon criteria. Patients randomized to losartan discontinued less than those randomized to atenolol. Multivariate analyses showed that older age, male gender, FRS, Sokolow-Lyon criteria, atenolol treatment as well as a history of pre-study myocardial infarction, cerebral vascular disease, peripheral vascular disease, and atrial fibrillation as well as lower levels of hemoglobin, higher serum creatinine and lower cholesterol independently predicted discontinuation. Conclusions: Patients discontinued during the first part of the study mainly due to a clinical adverse event. Patients who discontinued the study drug had, on average, more previous and concurrent cardiovascular disease than those who continued until the study ended. Thus, too high risk in an outcome study implies early drug discontinuation and thus reduction in the study power.