Clinical Question: Does valsartan or the combination of valsartan and captopril offer benefits over captopril alone after myocardial infarction?

Setting: Inpatient (any location) with outpatient follow-up

Study Design: Randomized controlled trial (double-blinded)

Synopsis: Angiotensin-converting enzyme inhibitors are known to improve outcomes after acute myocardial infarction, especially in patients with left ventricular dysfunction. It makes sense that angiotensin-receptor blockers might prove similarly beneficial, and that the combination may provide some incremental benefit over use of either drug alone.

This multicenter trial included adults with an acute myocardial infarction in the previous 10 days, evidence of left ventricular dysfunction, serum creatinine level less than 2.5 mg per dL (221 μmol per L), and a systolic blood pressure of at least 100 mm Hg. Randomization and allocation concealment appear to have been done correctly, and outcomes were judged by a group unaware of treatment assignment.

Patients were randomized to treatment with valsartan (n = 4,909), captopril (n = 4,909), or both (n = 4,885), and all doses were given orally. The three groups of patients were followed for a mean of 24.7 months. Valsartan was given initially at 20 mg once a day; the dosage was then increased with a goal of achieving 80 mg twice a day during the initial hospitalization and 160 mg twice a day by the three-month follow-up visit. Similarly, captopril was started at 6.25 mg once a day, and the dosage was advanced to 25 mg three times a day during the initial hospitalization and 50 mg three times a day by the visit at three months. Finally, the group who received both medications started with valsartan in a dosage of 20 mg per day plus captopril in a dosage of 6.25 mg per day. During hospitalization, the dosage was increased to 40 mg of valsartan twice a day plus 25 mg of captopril three times a day, and at three months patients were given 80 mg of valsartan twice a day plus 50 mg of captopril three times a day. At the end of one year, the average daily dosage was 247 mg in the valsartan group, 117 mg in the captopril group, and 116 mg of valsartan and 107 mg of captopril in the combined group. These dosages are higher than many patients achieve in usual practice.

Analysis was by intention to treat for the primary outcome of all-cause mortality. The groups were similar in all-cause mortality (i.e., 19.9 percent for valsartan, 19.5 percent for captopril, 19.3 percent for both). The likelihood of cardiovascular morbidity and mortality also was similar (i.e., 32.8 percent for valsartan, 33.4 percent for captopril, 32.3 percent for both). The percentage of patients no longer taking the study medication after one year was higher in the valsartan plus captopril group than in either group taking only one of the medications (19.8 percent for both, 15.3 percent for valsartan, 16.8 percent for captopril).

Adverse events were most likely in the valsartan plus captopril group (28.9 versus 22.8 percent for valsartan, and 21.8 percent for captopril; P <.05). Patients in the valsartan group experienced more hypotension (15.1 versus 11.9 percent; P <.05; number needed to harm [NNH] = 30) and renal problems (4.9 versus 3.0 percent; P <.05; NNH = 54) than patients in the captopril group. Cough (1.7 versus 5.0 percent; P <.05; NNH = 33) was less common in the valsartan group. Angioedema was rare (0.2 percent for valsartan, 0.5 percent for captopril, 0.5 percent for both medications), and patients never required intubation.

Bottom Line: Captopril and valsartan are similarly effective when given to patients with acute myocardial infarction and left ventricular dysfunction. The combination of the two drugs is no more effective and is associated with more adverse effects. Captopril has the advantage of being much less expensive and of causing less hypotension and fewer renal problems, although it does cause slightly increased cough (NNH = 30). (Level of Evidence: 1b)