Prospective Randomized Trial of Enalapril to Reverse Ventricular Enlargement - PRESERVE

Description:

Enalapril vs. nifedipine for LV mass in left ventricular hypertrophy.

Hypothesis:

Whether angiotensin-converting enzyme (ACE) inhibition is more effective than calcium channel blockade for promoting regression of left ventricular hypertrophy (LVH) and normalizing left ventricular (LV) diastolic filling.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 291
Mean Follow Up: 12 months
Mean Patient Age: 65
Female: 32

Patient Populations:

LV mass index of ≥116 gm/m² or ≥104 gm/m² for women ≥60 years on screening echocardiography
Moderately hypertensive

Primary Endpoints:

Change in LV mass at 12 months

Secondary Endpoints:

Cardiac index and heart rate at 12 months

Drug/Procedures Used:

Once daily enalapril or nifedipine XL.

Principal Findings:

LV mass was substantially reduced in both groups at 6 months (approximately 16 gm/m²) without any obvious further change at 12 months. Subgroup analysis of changes in LV mass failed to detect any group more likely to benefit from one agent compared to the other, with all groups showing significant results or strong beneficial trends with therapy. Relative wall thickness decreased significantly, but did so in a step-wise fashion over time, decreasing 0.02 cm from baseline to 6 months then decreasing another 0.02 cm from 6 months to 12 months. This more gradual decrease in relative wall thickness suggests that LV remodeling continues even after the first reduction in ventricular mass.

Both treatments led to substantial and sustained blood pressure reduction in both arms (mean reduction: 22 mmHg systolic and 12 mmHg diastolic), although the blood pressure response was seen earlier in the nifedipine group.

Both groups also showed a small but significant reduction in cardiac index from baseline to 12 months (2.7±0.8 to 2.5±0.6, p<0.001), indicating that any volume component to the hypertension and LVH stimulation was equally reversed by either agent. This was important because early studies with short-acting dihydropyridine agents suggested a substitution of volume load for pressure overload with therapy.
Both drugs were well-tolerated with >70% of patients in both arms remaining on assigned blinded medication and completing 12-month follow up.

Interpretation:

Previous studies of LV mass have been small, of short duration, and possibly confounded by regression to the mean. Some investigators have hypothesized that ACE inhibition would have a greater impact on LV mass compared to calcium channel blockade. However, this study suggests that therapy with ACE inhibition and calcium channel blockade both appear to decrease LV mass in patients with left ventricular hypertrophy. The effect appears by 6 months, with no further changes at up to 1 year.

References:

1. Circulation 1998;98(Suppl I):I-29. Preliminary results

Clinical Topics: Noninvasive Imaging, Prevention, Echocardiography/Ultrasound, Hypertension

Keywords: Hypertrophy, Left Ventricular, Enalapril, Follow-Up Studies, Research Personnel, Coronary Disease, Nifedipine, Hypertension, Calcium Channel Blockers, Echocardiography


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