Meta-analysis: Blood pressure lowering reduces left ventricular mass index in essential hypertension
ACP J Club. 1996 Nov-Dec;125:61. doi:10.7326/ACPJC-1996-125-3-061
Schmieder RE, Martus P, Klingbeil A. Reversal of left ventricular hypertrophy in essential hypertension. A meta-analysis of randomized double-blind studies. JAMA. 1996 May 15; 275:1507-13.
To evaluate determinants for, and effectiveness of, different antihyper-tensive drugs in attaining regression of left ventricular (LV) hypertrophy in essential hypertension.
Studies were identified by searching MEDLINE, DIMDI, RINGDOC, ADIS, and EMBASE (through to July 1995) using the keywords cardiac, heart, ventricular hypertrophy, wall thickness, ventricular or cardiac mass, arterial hypertension, man, drug treatment, and reversal or reduction and by reviewing Current Contents, textbooks, and review articles.
Studies were selected if they were randomized, double-blind, controlled trials; had ≥ 7 patients with untreated essential hypertension in each treatment group; treatment duration was ≥ 4 weeks; LV mass was evaluated by serial echocardiographic studies; and the antihypertensive agent evaluated was a diuretic, β-blocker, α-blocker, calcium channel blocker, or angiotensin-converting enzyme (ACE) inhibitor.
Data were extracted on number of patients; race; age; previous antihypertensive therapy; type, dose, and duration of antihypertensive therapy in the trial; pretreatment systolic and diastolic blood pressure (BP) and associated changes; and pretreatment LV mass index and LV wall thickness and associated changes.
39 studies were included; 189 patients were allocated to placebo and 1205 to active drugs. LV mass index was decreased by 8.7% in patients receiving antihypertensive agents compared with a 2.0% decrease in patients receiving placebo (P = 0.03). The mean reduction in systolic and diastolic BP was also greater in patients treated with active drugs. Determinants for regression of LV hypertrophy were the magnitude of the decrease in systolic and diastolic BP, the duration of treatment, and the pretreatment LV mass index. After adjustment for treatment duration, ACE inhibitors decreased LV mass index by 13.3% (CI 9.9% to 16.8%), calcium channel blockers by 9.3% (CI 5.5% to 13.1%), β-blockers by 5.5% (CI 2.3% to 8.6%), and diuretics by 6.8% (CI 3.0% to 10.7%). ACE inhibitors led to a greater decrease in LV mass index than did diuretics (P = 0.01). No differences existed between ACE inhibitors and calcium channel blockers or among diuretics, β-blockers, and calcium channel blockers.
With blood pressure lowering, the decrease in LV hypertrophy is determined by pretreatment LV mass index, magnitude of blood pressure lowering, duration of therapy, and antihypertensive drug class. ACE inhibitors are the most effective drugs for decreasing LV mass in essential hypertension.
Source of funding: No external funding.
For article reprint: Dr. R.E. Schmieder, Medizinische Klinik IV, Universität Erlangen-Nürnberg, Breslauer Strasse 201, 90471 Nuremberg, Germany. FAX 49-911-398-3183.
Unlike other cardiovascular risk factors, the regression of LV hypertrophy lacks a definitive therapeutic study of its benefits assessed in terms of morbidity and mortality. Studies that evaluate surrogate end points, such as those reviewed by Schmieder and colleagues, may provide some direction about the most effective medications.
Earlier reviews included 2 comprehensive overviews from Sweden (1) and the United Kingdom (2), each with > 100 studies. Although the meta-analysis of randomized, double-blind trials by Schmieder and colleagues was more rigorous and only 39 studies were included, the conclusions were similar. Rank order for regression of LV hypertrophy is consistent: ACE inhibitors, calcium channel blockers, β-blockers, and diuretics.
The authors of this meta-analysis excluded several trials because change in LV mass was not their primary objective or because the study design did not allow comparison between various antihypertensive drugs without interactions of other therapeutic interventions. Hence, the monotherapy comparison of 6 drug classes in the Treatment of Mild Hypertension Study (TOMHS) (3) was rejected. TOMHS, which included patients who did not have LV hypertrophy (mean LV mass 102 g/m2), makes the apparently contradictory conclusion that the diuretic chlorthalidone, when used in conjunction with an intensive nutrition-hygiene regimen, was the only drug to reduce LV mass. The meta-analysis by Cruickshank and colleagues (2) included less recent data about diuretic and β-blocker combinations and concluded that these were as effective as ACE-inhibitor monotherapy.
Compelling reasons exist that ACE inhibitors should be more effective for reducing LV mass. I hope that this translates into clinical benefit. Because most patients with LV hypertrophy are likely to require at least 2 drugs for blood pressure control, it is reasonable to conclude that 1 of the medications should be an ACE inhibitor; however, "the possible prognostic implications need to be evaluated in controlled prospective trials" (1). Fortunately, such trials are under way.
S. George Carruthers, MD
University of Western OntarioLondon, Ontario, Canada