Helmut Schumacher

Telmisartan, Ramipril, or Both in Patients at High Risk for Vascular Events

BACKGROUND In patients who have vascular disease or high-risk diabetes without heart failure, angiotensin-converting-enzyme (ACE) inhibitors reduce mortality and morbidity from cardiovascular causes, but the role of angiotensin-receptor blockers (ARBs) in such patients is unknown. We compared the ACE inhibitor ramipril, the ARB telmisartan, and the combination of the two drugs in patients with vascular disease or high-risk diabetes. METHODS After a 3-week, single-blind run-in period, patients underwent double-blind randomization, with 8576 assigned to receive 10 mg of ramipril per day, 8542 assigned to receive 80 mg of telmisartan per day, and 8502 assigned to receive both drugs (combination therapy). The primary composite outcome was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure. RESULTS Mean blood pressure was lower in both the telmisartan group (a 0.9/0.6 mm Hg greater reduction) and the combination-therapy group (a 2.4/1.4 mm Hg greater reduction) than in the ramipril group. At a median follow-up of 56 months, the primary outcome had occurred in 1412 patients in the ramipril group (16.5%), as compared with 1423 patients in the telmisartan group (16.7%; relative risk, 1.01; 95% confidence interval [CI], 0.94 to 1.09). As compared with the ramipril group, the telmisartan group had lower rates of cough (1.1% vs. 4.2%, P<0.001) and angioedema (0.1% vs. 0.3%, P=0.01) and a higher rate of hypotensive symptoms (2.6% vs. 1.7%, P<0.001); the rate of syncope was the same in the two groups (0.2%). In the combination-therapy group, the primary outcome occurred in 1386 patients (16.3%; relative risk, 0.99; 95% CI, 0.92 to 1.07); as compared with the ramipril group, there was an increased risk of hypotensive symptoms (4.8% vs. 1.7%, P<0.001), syncope (0.3% vs. 0.2%, P=0.03), and renal dysfunction (13.5% vs. 10.2%, P<0.001). CONCLUSIONS Telmisartan was equivalent to ramipril in patients with vascular disease or high-risk diabetes and was associated with less angioedema. The combination of the two drugs was associated with more adverse events without an increase in benefit. (ClinicalTrials.gov number, NCT00153101 [ClinicalTrials.gov].).

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, telmisartans 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.

Prognostic value of blood pressure in patients with high vascular risk in the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial study

Background Hypertension guidelines advise aggressive blood pressure (BP) lowering in patients with diabetes or high cardiovascular risk, but supporting evidence is limited. We analysed the impact of BP on cardiovascular events in well treated high-risk patients enrolled in a large clinical trial (Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial). Methods Twenty-five thousand five hundred and eighty-eight patients with atherosclerotic disease or diabetes with organ damage, tolerant to angiotensin-converting enzyme inhibitors, were randomized to ramipril, telmisartan or both. We related the primary composite outcome and its components to: baseline SBP; SBP changes from baseline to event; and average in-trial SBP. Results The risk of myocardial infarction did not increase with baseline SBP and was unaffected by subsequent SBP change. In contrast, stroke risk progressively increased with baseline SBP (P for trend <0.0001) and decreased with reduction. In patients with baseline SBP less than 130 mmHg, adjusted for several covariates, cardiovascular mortality increased with further SBP reduction (P < 0.0001). A J-curve (nadir around 130 mmHg) occurred in the relationship between in-treatment SBP and all outcomes except stroke. Conclusion In high-risk patients, the benefits from SBP lowering below 130 mmHg are driven mostly by a reduction of stroke; myocardial infarction is unaffected and cardiovascular mortality is unchanged or increased. Future trials should be designed to test the value of SBP lowering in high-risk patients with SBP in the range of 130–150 mmHg.

Diagnosis and treatment of patients with stroke in a mobile stroke unit versus in hospital: a randomised controlled trial.

BACKGROUND Only 2-5% of patients who have a stroke receive thrombolytic treatment, mainly because of delay in reaching the hospital. We aimed to assess the efficacy of a new approach of diagnosis and treatment starting at the emergency site, rather than after hospital arrival, in reducing delay in stroke therapy. METHODS We did a randomised single-centre controlled trial to compare the time from alarm (emergency call) to therapy decision between mobile stroke unit (MSU) and hospital intervention. For inclusion in our study patients needed to be aged 18-80 years and have one or more stroke symptoms that started within the previous 2·5 h. In accordance with our week-wise randomisation plan, patients received either prehospital stroke treatment in a specialised ambulance (equipped with a CT scanner, point-of-care laboratory, and telemedicine connection) or optimised conventional hospital-based stroke treatment (control group) with a 7 day follow-up. Allocation was not masked from patients and investigators. Our primary endpoint was time from alarm to therapy decision, which was analysed with the Mann-Whitney U test. Our secondary endpoints included times from alarm to end of CT and to end of laboratory analysis, number of patients receiving intravenous thrombolysis, time from alarm to intravenous thrombolysis, and neurological outcome. We also assessed safety endpoints. This study is registered with ClinicalTrials.gov, number NCT00153036. FINDINGS We stopped the trial after our planned interim analysis at 100 of 200 planned patients (53 in the prehospital stroke treatment group, 47 in the control group), because we had met our prespecified criteria for study termination. Prehospital stroke treatment reduced the median time from alarm to therapy decision substantially: 35 min (IQR 31-39) versus 76 min (63-94), p<0·0001; median difference 41 min (95% CI 36-48 min). We also detected similar gains regarding times from alarm to end of CT, and alarm to end of laboratory analysis, and to intravenous thrombolysis for eligible ischaemic stroke patients, although there was no substantial difference in number of patients who received intravenous thrombolysis or in neurological outcome. Safety endpoints seemed similar across the groups. INTERPRETATION For patients with suspected stroke, treatment by the MSU substantially reduced median time from alarm to therapy decision. The MSU strategy offers a potential solution to the medical problem of the arrival of most stroke patients at the hospital too late for treatment. FUNDING Ministry of Health of the Saarland, Germany, the Werner-Jackstädt Foundation, the Else-Kröner-Fresenius Foundation, and the Rettungsstiftung Saar.

Changes in Albuminuria Predict Mortality and Morbidity in Patients with Vascular Disease

The degree of albuminuria predicts cardiovascular and renal outcomes, but it is not known whether changes in albuminuria also predict similar outcomes. In two multicenter, multinational, prospective observational studies, a central laboratory measured albuminuria in 23,480 patients with vascular disease or high-risk diabetes. We quantified the association between a greater than or equal to twofold change in albuminuria in spot urine from baseline to 2 years and the incidence of cardiovascular and renal outcomes and all-cause mortality during the subsequent 32 months. A greater than or equal to twofold increase in albuminuria from baseline to 2 years, observed in 28%, associated with nearly 50% higher mortality (HR 1.48; 95% CI 1.32 to 1.66), and a greater than or equal to twofold decrease in albuminuria, observed in 21%, associated with 15% lower mortality (HR 0.85; 95% CI 0.74 to 0.98) compared with those with lesser changes in albuminuria, after adjustment for baseline albuminuria, BP, and other potential confounders. Increases in albuminuria also significantly associated with cardiovascular death, composite cardiovascular outcomes (cardiovascular death, myocardial infarction, stroke, and hospitalization for heart failure), and renal outcomes including dialysis or doubling of serum creatinine (adjusted HR 1.40; 95% CI 1.11 to 1.78). In conclusion, in patients with vascular disease, changes in albuminuria predict mortality and cardiovascular and renal outcomes, independent of baseline albuminuria. This suggests that monitoring albuminuria is a useful strategy to help predict cardiovascular risk.

Effect of telmisartan on renal outcomes: a randomized trial.

Context Few trials have evaluated whether angiotensin-receptor blockers (ARBs) prevent renal disease in people without proteinuria. Contribution In this trial, patients with cardiovascular disease or diabetes, but without macroalbuminuria or heart failure, were randomly assigned to receive telmisartan or placebo. During 4 to 5 years of follow-up, telmisartan recipients had albuminuria less often but had doubling of serum creatinine and slight decreases in estimated glomerular filtration rate more often than placebo recipients. Few patients in either group required dialysis. Implication The effects of ARBs on renal variables are complicated, but no strong evidence indicates that they prevent clinically important renal disease in patients without proteinuria. The Editors The TRANSCEND (Telmisartan Randomised Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease) study examined cardiovascular outcomes with telmisartan, an angiotensin-receptor blocker (ARB), compared with placebo in people at high vascular risk who were intolerant of angiotensin-converting enzyme (ACE) inhibitors. Telmisartan had no statistically significant effect on the primary cardiovascular outcome, but it reduced the risk for the secondary composite outcome of cardiovascular death, myocardial infarction, and stroke to a moderate extent and had no effect on cardiovascular or total mortality (1). Renal outcomes were prespecified, important secondary outcomes of the TRANSCEND study, because a growing number of patients with atherosclerotic vascular disease are starting renal replacement therapy (2). For example, in a German registry, the proportion of individuals with vascular causes of nephropathy leading to long-term dialysis increased from 12% in 1995 to 23% in 2005 (3). Drugs used to reduce vascular events may also affect the kidney, so the effects of such drugs on renal outcomes in people with vascular disease are relevant. Angiotensin-receptor blockers reduce elevated blood pressure (4) and urinary protein excretion (5), which are both considered to be surrogate variables of renal benefit. Large trials in patients with overt diabetic nephropathy have demonstrated that ARBs reduce the rate of dialysis and doubling of serum creatinine (6, 7). The impact of ARBs on renal outcomes in other patients is not reliably known. This prespecified analysis of the TRANSCEND study (1) examined the effects of telmisartan on renal function in a large sample that was intolerant of ACE inhibitors and had vascular disease but not macroalbuminuria. The composite renal outcome was dialysis or doubling of serum creatinine. We also report changes in estimated glomerular filtration rate (GFR) and albuminuria. Methods Design Overview We enrolled and randomly assigned participants age 55 years or older with documented cardiovascular disease or diabetes with end-organ damage who could not tolerate ACE inhibitors between November 2001 and May 2004 to receive telmisartan, 80 mg/d, or matching placebo along with standard treatment. Follow-up was completed by March 2008. The main trial primary outcome, reported elsewhere (1), was the composite of myocardial infarction, stroke, cardiovascular death, and hospitalization for heart failure. We report the prespecified renal outcomes in this article. The ethics committees at all participating institutions and the regulatory authorities in each country approved the study protocol, and each participant provided written informed consent. Setting and Participants In 630 centers in 40 countries, we enrolled 5926 patients age 55 years or older who were intolerant of ACE inhibitors if they had coronary, peripheral, or cerebrovascular disease or diabetes with end-organ damage (1, 8). We defined ACE inhibitor intolerance as discontinuation of an ACE inhibitor for a documented reasonmost commonly cough (88.2%), symptomatic hypotension (4.1%), angioedema (1.3%), and renal dysfunction (1%) (1, 8). We excluded patients who, according to the clinical investigators, needed an ARB; were known to be hypersensitive or intolerant to ARBs; or had heart failure, significant valvular or cardiac outflow tract obstruction, constrictive pericarditis, complex congenital heart disease, unexplained syncope, planned cardiac surgery, cardiac revascularization in the previous 3 months, systolic blood pressure of 160 mm Hg or greater, heart transplantation, subarachnoid hemorrhage, known significant renal artery stenosis (formal exclusion not required), serum creatinine levels greater than 265 mol/L (>3.0 mg/dL), or hepatic dysfunction. The Appendix Table lists all exclusion criteria. Macroalbuminuria (urinary albumincreatinine ratio [UACR] >33.9 mg/mmol) was an exclusion criterion, but it was detected at baseline in 78 participants (1.44%) when the urine was analyzed centrally. Before entering the study, 1773 participants (29.9%) were receiving or had received ARBs. Appendix Table. Exclusion Criteria The study was coordinated by the Population Health Research Institute at McMaster University, Hamilton, Ontario, Canada. The steering committee designed and oversaw the trial and implemented an operations committee, an independent data safety and monitoring board, and an end point adjudication committee. Clinical sites in 40 countries, selected by the national coordinators, used a wide variety of recruitment strategies, including chart review, referral from other physicians, and mass mailing. Randomization and Interventions After a 3- to 4-week run-in phase, participants were randomly assigned to telmisartan, 80 mg/d, or placebo. During the run-in phase, all participants received single-blind placebo for 1 week followed by telmisartan, 80 mg/d, for 2 to 3 weeks. Of 6666 participants entering the run-in phase, 11 (0.2%) withdrew because of elevated serum creatinine levels and 26 (0.4%) withdrew because of elevated serum potassium levels. Figure 1 shows the study flow diagram and reasons for exclusion; baseline characteristics of the participants are published elsewhere (1). Participants were randomly assigned by telephone through a central automated system. Randomization was stratified by hospital or clinic. All participants and trial investigators were blinded to randomized treatment. Tablets identical in color, shape, and taste were provided in blister packs. Unblinded data were made available exclusively to the independent data safety and monitoring board by a statistician who was independent of the trial. Figure 1. Study flow diagram. All participants received randomized therapy and were followed, except for 18 (0.3%) who were followed until the end of the study or until a primary event occurred. The number of patients considered for the trial who did not enter the run-in phase is unknown. A figure showing trial follow-up and cardiovascular outcomes is published elsewhere (1). Progression of proteinuria was defined as new microalbuminuria, macroalbuminuria, or both. eGFR= estimated glomerular filtration rate; UACR= urinary albumincreatinine ratio. Outcomes and Measurements In August 2007, before completion of the TRANSCEND study, we developed a statistical analysis plan for the renal outcomes. As in other large renal trials, the primary composite outcome was defined as the first occurrence of dialysis, renal transplantation, doubling of serum creatinine, or death (6, 7, 9). No cases of renal transplantation were reported in this trial. The secondary renal outcome was the composite of dialysis or doubling of serum creatinine. After completion of the analysis, deatha nonspecific outcomeoutnumbered the other components of the primary outcome by 4-fold. Therefore, we determined the secondary outcome as the composite outcome measure of this analysis. Further outcomes were components of the composite outcome, changes in estimated GFR and UACR, and progression of proteinuria (defined as development of new micro- or macroalbuminuria), as well as the original primary composite outcome and the composite of dialysis; doubling of serum creatinine; or development of new microalbuminuria, macroalbuminuria, or both. Dialysis was categorized as short-term (2 months) or long-term (>2 months). Such information was missing in 1 patient. Urinary albumin and creatinine were measured centrally (10), and serum creatinine was measured locally at study sites. The estimated GFR was calculated from serum creatinine by using the 4-variable Modification of Diet in Renal Disease Study formula (11). Serum creatinine values below 35 mol/L (<0.4 mg/dL) were considered implausible, and we excluded participants with such values from the analysis (10 patients at baseline and 15 patients at follow-up). Information about dialysis was recorded at each visit. Follow-up Procedures and Monitoring We followed participants after 6 weeks, 6 months, and every 6 months thereafter for a mean of 56 months. At each visit, we collected information about adverse events, including dialysis; adherence to trial medication; and outcomes. We began data management as soon as data had been submitted, usually within 1 week of the patient visit. The data were sent through the datafax system and examined for ranges, plausibility, and missing data. Queries were sent to the investigator until responses were obtained. We measured serum creatinine before the run-in phase, 6 weeks after randomization, after 2 years, and at the end of the study, and we measured UACR before the run-in phase, at 2 years, and at the penultimate visit in a first morning urine sample. A UACR between 3.4 and 33.9 mg/mmol was defined as microalbuminuria and a value greater than 33.9 mg/mmol (approximately 300 mg/g creatinine) as macroalbuminuria. A blinded central committee, using standardized criteria, adjudicated all deaths and primary outcomes. After trial conclusion, a questionnaire was sent to all sites that reported dialysis to obtain information about duration of dialysis. Statistical Analysis The original sample size esti

Effect of diabetes on lower urinary tract symptoms in patients with benign prostatic hyperplasia

PURPOSE Several studies have suggested a specific association between the presence and/or symptom intensity of benign prostatic hyperplasia (BPH) and diabetes but to our knowledge no definitive conclusion has been reached. Therefore, we examined the intensity of lower urinary tract symptoms in a large cohort of men with BPH with and without diabetes. We then determined whether the alpha1-adrenoceptor antagonist tamsulosin similarly improved lower urinary tract symptoms in patients with BPH with or without diabetes. MATERIALS AND METHODS The International Prostate Symptom Score (I-PSS), maximum flow rate and post-void residual were determined in 9,856 men with clinically diagnosed BPH, of whom 1,290 also had diabetes, at baseline and after a 12 week, open label course of 0.4 mg. tamsulosin daily. RESULTS Logistic regression of the baseline data indicated that older age and I-PSS were independently associated with a statistically significant increase in the odds ratio of having diabetes. Accordingly, diabetics had a significantly greater baseline I-PSS and smaller maximum flow rate than non-diabetic patients on age-adjusted analysis, while residual urine was not significantly altered. Tamsulosin markedly improved lower urinary tract symptoms. The extent of improvement was similar in diabetic and nondiabetic patients, although some slight differences reached statistical significance due to large patient numbers. CONCLUSIONS The severity of lower urinary tract symptoms in patients with BPH and the likelihood of having diabetes are significantly associated. Within the limitations of an open label, observational study tamsulosin appears to reduce lower urinary tract symptoms similarly in patients with BPH with or without diabetes.

Mexiletine in the Treatment of Diabetic Neuropathy

OBJECTIVE To prove the efficacy of mexiletine in painful diabetic neuropathy. RESEARCH DESIGN AND METHODS Treatment was provided in three dosages. For pain measurements, a VAS and McGills verbal rating scale were chosen. Ninety-five patients were included in the study. RESULTS A global assessment of the VAS among patients showed no differences between mexiletine treatment and placebo. The total evaluation (PRIT) of the McGill scale fell just below the level of significance. More specific exploratory evaluations of subclasses of the McGill scale, representing different degrees of pain, gave remarkable differences between mexiletine and placebo in sensory and miscellaneous items. In special subgroups, which were formed according to types and courses of complaints compiled at the beginning of this evaluation, the substantial advantages of the mexiletine treatment were shown with both the VAS and the McGill scale. CONCLUSIONS Evidence strongly indicates that, in particular, those patients with stabbing or burning pain, heat sensations, or formication will benefit most by mexiletine therapy. Concerning the dosage, a medium regimen of 450 mg/day seems to be appropriate. With an increase in the antiarryhthmic dosage level, the efficacy does not rise proportionally. Mexiletine proved to be a safe therapy with negligible side effects at the medium dose range, even < placebo; and remarkably, no cardiovascular side effects were noted. Further studies should avoid global assessments and pay more attention to the variety of complaints and quality of life.

Safety and Efficacy of Low Blood Pressures Among Patients With Diabetes: Subgroup Analyses From the ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial)

OBJECTIVES We sought to determine whether the blood pressure (BP) levels at which cardiovascular (CV) protection is achieved differ between diabetic and nondiabetic patients from the ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial). BACKGROUND Greater absolute benefits of BP reductions have been claimed for diabetic as compared with nondiabetic patients. METHODS A total of 25,584 patients (9,603 diabetic), older than 55 years, at high CV risk were randomized to ramipril, telmisartan, or both and observed for 4.6 years. We pooled the treatment arms to examine the relationships between BP and the primary composite outcome (CV death, nonfatal myocardial infarction or stroke, or hospitalized heart failure) and its components. RESULTS The primary outcome occurred in 1,938 (20.2%) diabetic patients and in 2,276 (14.2%) nondiabetic patients. Compared with nondiabetic patients, diabetic patients had a significantly higher risk for the primary endpoint (hazard ratio [HR]: 1.48; 95% confidence interval [CI]: 1.38 to 1.57) and CV death (HR: 1.56; 95% CI: 1.42 to 1.71); myocardial infarction (HR: 1.30 (95% CI: 1.17 to 1.46); stroke (HR: 1.39; 95% CI: 1.23 to 1.56); and congestive heart failure hospitalization (HR: 2.06; 95% CI: 1.82 to 2.32). The CV risk was significantly higher in diabetic than in nondiabetic patients regardless of the systolic BP changes during treatment. In both diabetic and nondiabetic patients, progressively greater systolic BP reductions were accompanied by reduced risk for the primary outcome only if baseline systolic BP levels ranged from 143 to 155 mm Hg; except for stroke, there was no benefit in fatal or nonfatal CV outcomes by reducing systolic BP below 130 mm Hg. CONCLUSIONS The relationship between BP and overall CV risk had a similar pattern in diabetic and nondiabetic patients over a wide range of baseline and in-treatment BP values although, for the same systolic BP, a higher risk is observed in diabetic patients.

Blood Pressure Targets Recommended by Guidelines and Incidence of Cardiovascular and Renal Events in the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET)

Background— Hypertension treatment guidelines recommend that blood pressure (BP) be lowered to <140/90 mm Hg, but that a reduction to <130/80 mm Hg be adopted in patients at high cardiovascular (CV) risk. We investigated the CV and renal benefits associated with these BP targets in the high-CV-risk population of the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET). Methods and Results— Patients were divided into 4 groups according to the proportion of in-treatment visits before the occurrence of an event (<25%–>75%) in which BP was reduced to <140/90 or <130/80 mm Hg. After adjustment for demographic and clinical variables, a progressive increase in the proportion of visits in which BP was reduced to <140/90 or <130/80 mm Hg was associated with a progressive reduction in the risk of stroke, new onset of microalbuminuria or macroalbuminuria, and return to normoalbuminuria in albuminuric patients. An increased frequency of BP control to either target did not have any consistent effect on the adjusted risk of myocardial infarction and heart failure. The adjusted risk of CV events was reduced by increasing the frequency of BP control to <140/90 mm Hg, but not to <130/80 mm Hg. Similar findings were obtained for the achievement of the BP target in the visit preceding a CV event. Conclusion— The more frequent achievement of the BP targets recommended by guidelines led to cerebrovascular and renal protection, but did not increase cardiac protection. Overall, CV protection was favorably affected by the less tight but not by the tighter BP target. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00153101.