Principal Findings:

After a 1-month run-in phase, 5,926 patients were randomized, 2,954 to telmisartan and 2,972 to placebo. The majority of the patients (61.1%) were European, whereas 21.3% were Asian; only 1.8% were African in origin. The major reason for discontinuation of ACE inhibitors in these patients was cough (88.2%), whereas angioedema or anaphylaxis was noted in 1.3% of the patients. About 76.4% of the patients had hypertension, 74.6% had coronary artery disease, 22% had a history of stroke or transient ischemic attack, and 35.7% had diabetes. By the end of the study, a small proportion of the patients were on ARBs other than telmisartan (6.7%). As expected, a greater proportion of patients in the placebo arm were given nonstudy blood pressure–lowering medications over the course of the study, whereas the use of statins and antiplatelet agents was similar.

The mean blood pressure was lower in the telmisartan group at all time points studied, including at the end of the study (3.2/1.3 mm Hg). The primary endpoint of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure was similar between the ARB and placebo arms (15.7% vs. 17.0%, hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.81-1.05, p = 0.22). The incidence of cardiovascular death, myocardial infarction, or stroke was lower in the telmisartan group (13.0% vs. 14.8%, HR 0.87, 95% CI 0.76-1.0, p = 0.048). The separation of the survival curves was apparent only after about 1.5 years or so. The reduction in this composite endpoint was driven primarily by a reduction in the incidence of myocardial infarction (3.9% vs. 5.0%, p = 0.06), whereas the incidence of cardiovascular death, stroke, and heart failure seemed to be fairly similar.

Of the secondary outcomes, there was a slight reduction in the incidence of new diabetes mellitus (11.0% vs. 12.8%, p = 0.08), left ventricular hypertrophy (5.0% vs. 7.9%, p < 0.001), and any cardiovascular hospitalization (30.3% vs. 33%, p = 0.025). There was no difference in the incidence of all-cause mortality (12.3% vs. 11.7%, p = 0.49). No difference was also noted in the incidence of a composite renal outcome (dialysis, doubling of serum creatinine, changes in estimated GFR, or changes in albuminuria) (1.96% vs. 1.55%, p = 0.20).

The total number of study drug discontinuations was similar between the two arms (36.9% vs. 38.5%, p = 0.22), although there was a near doubling of discontinuations in the telmisartan arm due to renal abnormalities (0.8% vs. 0.4%, p = 0.07) and symptomatic hypotension (1% vs. 0.5%, p = 0.05), whereas the incidence of angioedema was similar (0.1%).