Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial.

BACKGROUND: Angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors are known to reduce proteinuria. Their combination might be more effective than either treatment alone, but long-term data for comparative changes in renal function are not available. We investigated the renal effects of ramipril (an ACE inhibitor), telmisartan (an ARB), and their combination in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage. METHODS: The trial ran from 2001 to 2007. After a 3-week run-in period, 25 620 participants were randomly assigned to ramipril 10 mg a day (n=8576), telmisartan 80 mg a day (n=8542), or to a combination of both drugs (n=8502; median follow-up was 56 months), and renal function and proteinuria were measured. The primary renal outcome was a composite of dialysis, doubling of serum creatinine, and death. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00153101. FINDINGS: 784 patients permanently discontinued randomised therapy during the trial because of hypotensive symptoms (406 on combination therapy, 149 on ramipril, and 229 on telmisartan). The number of events for the composite primary outcome was similar for telmisartan (n=1147 [13.4%]) and ramipril (1150 [13.5%]; hazard ratio [HR] 1.00, 95% CI 0.92-1.09), but was increased with combination therapy (1233 [14.5%]; HR 1.09, 1.01-1.18, p=0.037). The secondary renal outcome, dialysis or doubling of serum creatinine, was similar with telmisartan (189 [2.21%]) and ramipril (174 [2.03%]; HR 1.09, 0.89-1.34) and more frequent with combination therapy (212 [2.49%]: HR 1.24, 1.01-1.51, p=0.038). Estimated glomerular filtration rate (eGFR) declined least with ramipril compared with telmisartan (-2.82 [SD 17.2] mL/min/1.73 m(2)vs -4.12 [17.4], p<0.0001) or combination therapy (-6.11 [17.9], p<0.0001). The increase in urinary albumin excretion was less with telmisartan (p=0.004) or with combination therapy (p=0.001) than with ramipril. INTERPRETATION: In people at high vascular risk, telmisartan's effects on major renal outcomes are similar to ramipril. Although combination therapy reduces proteinuria to a greater extent than monotherapy, overall it worsens major renal outcomes.

Effect of atenolol on symptomatic ventricular arrhythmia without structural heart disease: a randomized placebo-controlled study.

BACKGROUND: Ventricular arrhythmia (VA) from the right ventricular outflow tract (RVOT) is a common problem. Symptomatic patients are usually treated with beta-blockers. There is little data on the systematic evaluation of the efficacy of beta-blocker. We determine the efficacy of atenolol in the treatment of symtomatic VA from RVOT compared with placebo. METHODS AND RESULTS: This was a randomized, double-blinded, placebo-controlled study. We prospectively studied 52 consecutive patients with symptomatic VA. Severity of symptoms, 24-hour ambulatory monitoring (AECG) and quality of life (QOL) were assessed at baseline and 1 month after atenolol. Exercise testing was performed at baseline. Average premature ventricular complex (PVC) count at baseline was 21,407 +/- 1740 beats per 24 hours, and 19% had ventricular tachycardia as measured by AECG. Results of this study showed that atenolol significantly decreased symptom frequency (P =.03), PVC count (P =.001) and average heart rate (P <.001) measured by AECG, whereas placebo significantly decreased symptom frequency (P =.002) but had no effect on PVC count (P =.78) or average heart rate (P =.44). Neither atenolol nor placebo had an effect on QOL. CONCLUSIONS: Atenolol improves symptoms and decreases PVC count from ambulatory monitoring. Placebo improved symptoms to the same extent as atenolol but had no effect on severity of VA. This might be the so-called placebo effect, which is a concern when treating patients or doing research on the effects of a drug.

Accuracy of magnetic resonance imaging in the diagnosis of coronary artery disease.

BACKGROUND: Coronary magnetic resonance angiography is a noninvasive method to visualize coronary arteries. The objective of this study was to determine the accuracy of coronary magnetic resonance imaging in the detection of coronary artery stenosis. METHOD: The authors studied 61 patients who were scheduled for their first diagnostic X-ray coronary angiography. Magnetic resonance imaging of the coronary arteries under free-breathing was performed prior to the catheterization schedule. The results were compared. RESULTS: Forty-one out of 61 patients (67.2%) had significant coronary stenosis of at least one major coronary artery. Sixteen (26.2%) had triple vessel disease. A total of 391 of 427 segments had interpretable image quality (91.6%). The diagnostic accuracy of the left main artery, left anterior descending artery, left circumflex artery, and right coronary artery was 96.7 per cent, 90 per cent, 80 per cent and 85.2 per cent respectively. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of the detection of any significant coronary disease were 97.6 per cent, 75 per cent, 91.2 per cent, 90.9 per cent and 92.3 per cent respectively. CONCLUSIONS: Coronary magnetic resonance imaging is an accurate non-invasive imaging technique in the detection of coronary artery stenosis.

In a subgroup of high-risk Asians, telmisartan was non-inferior to ramipril and better tolerated in the prevention of cardiovascular events.

BACKGROUND AND OBJECTIVES: Results of the recently published ONTARGET study (The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) showed that telmisartan (80 mg/day) was non-inferior to ramipril (10 mg/day) in reducing cardiovascular events. Clinicians in Asia doubt tolerability of these doses for their patients. We therefore analyzed data from this study and a parallel study TRANSCEND (Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease). Our objectives were to compare Asians and non-Asians with respect to the following: 1) Effectiveness of telmisartan vs. ramipril in reducing cardiovascular events;2) Proportions who reached the full dose of telmisartan, ramipril or placebo; and3) Proportions of overall discontinuations, and discontinuations due to adverse effects. METHOD: The ONTARGET study randomized 25,620 patients at risk of cardiovascular events to ramipril, telmisartan, or their combination. The primary composite endpoint was death caused by cardiovascular disease, acute MI, stroke, and hospitalization because of congestive heart failure. TRANSCEND randomized 5926 high-risk patients with a history of intolerance to ACE-inhibitors to telmisartan or placebo. The primary outcome was the same. In this substudy, we compared Asians and non-Asians as to how well they tolerated telmisartan (given in both studies) and ramipril (given in ONTARGET). RESULTS: 1) Telmisartan was non-inferior to ramipril in lowering the primary endpoint among Asians (RR = 0.92; 95% CI: 0.74, 1.13); 2) more Asians achieved the full dose of either drug; 3) less withdrew (overall); and 4) less withdrew for adverse effects. Furthermore, telmisartan was better tolerated than ramipril. This advantage was greater among Asians. CONCLUSION AND SIGNIFICANCE: Although Asians had lower BMI than non-Asians, Asians tolerated both drugs better. Regulatory agencies require reporting of safety and effectiveness data by ethnicity, but few comply with this requirement. This study shows that safety data in ethnic subgroups can help assess applicability of results to specific populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT00153101.