Heart Outcomes Prevention Evaluation Research Articles

The Differential Impact of Medical Therapy and Lifestyle Modification on Cardiovascular Health and Risk of Adverse Cardiovascular Events: A Narrative Review.

Cardiovascular diseases (CVDs) continueto be a worldwide health concern, requiring effective strategies for risk reduction. This article explores the extensive collaboration between medical therapy and lifestyle modifications in the management of CVDs, aiming to interpret whether a single approach holds the key to reducing major cardiovascular events. In the realm of pharmaceutical therapy, statins, beta-blockers, angiotensin-converting-enzyme (ACE) inhibitors, and antiplatelet agents have shown significant effectiveness, as evidenced by landmark trials such as Scandinavian Simvastatin Survival Study (4S) and Heart Outcomes Prevention Evaluation (HOPE). Concurrently, lifestyle adjustments, encompassing physical activity, dietary changes,and management of stress, emerge as indispensable elements in cardiovascular care. The article discusses the pivotal role of patient adherence, tailored approaches, and the synergistic impact of combining medical therapy and lifestyle modifications. Challenges, such as socioeconomic disparities and uncertainties in lipid management, underscore the need for ongoing research and precision medicine. Digital health interventions offer novel avenues for personalized care. Despite advancements, uncertainties persist regarding the optimal balance between medical and lifestyle interventions in lowering major cardiovascular event risks. This article emphasizes the ongoing evolution of cardiovascular care, highlighting the imperative need for evidence-based guidelines tailored to individual patient needs.

Lowering Nighttime Blood Pressure With Bedtime Dosing of Antihypertensive Medications: Controversies in Hypertension - Con Side of the Argument.

Lowering Nighttime Blood Pressure With Bedtime Dosing of Antihypertensive Medications: Controversies in Hypertension - Con Side of the Argument.

Clinical profile of isolated systolic hypertension in elderly

Isolated systolic hypertension is the most common hemodynamic form of hypertension in the elderly. With a rapidly aging population, the prevalence of hypertension, particularly isolated systolic hypertension, is increasing steadily. Isolated systolic hypertension is associated with substantial mortality and morbidity, particularly of cerebrovascular disease. It is a rapidly growing public health concern and its management continues to remain a challenge to practicing physicians. Recent studies like the Systolic Blood Pressure Intervention Trial (SPRINT) and Heart Outcomes Prevention Evaluation (HOPE)-3 have implications for antihypertensive therapy in general and for the management of isolated systolic hypertension in particular.

Antihypertensives and Statin Therapy for Primary Stroke Prevention: A Secondary Analysis of the HOPE-3 Trial.

The HOPE-3 trial (Heart Outcomes Prevention Evaluation–3) found that antihypertensive therapy combined with a statin reduced first stroke among people at intermediate cardiovascular risk. We report secondary analyses of stroke outcomes by stroke subtype, predictors, treatment effects in key subgroups. Using a 2-by-2 factorial design, 12 705 participants from 21 countries with vascular risk factors but without overt cardiovascular disease were randomized to candesartan 16 mg plus hydrochlorothiazide 12.5 mg daily or placebo and to rosuvastatin 10 mg daily or placebo. The effect of the interventions on stroke subtypes was assessed. Participants were 66 years old and 46% were women. Baseline blood pressure (138/82 mm Hg) was reduced by 6.0/3.0 mm Hg and LDL-C (low-density lipoprotein cholesterol; 3.3 mmol/L) was reduced by 0.90 mmol/L on active treatment. During 5.6 years of follow-up, 169 strokes occurred (117 ischemic, 29 hemorrhagic, 23 undetermined). Blood pressure lowering did not significantly reduce stroke (hazard ratio [HR], 0.80 [95% CI, 0.59–1.08]), ischemic stroke (HR, 0.80 [95% CI, 0.55–1.15]), hemorrhagic stroke (HR, 0.71 [95% CI, 0.34–1.48]), or strokes of undetermined origin (HR, 0.92 [95% CI, 0.41–2.08]). Rosuvastatin significantly reduced strokes (HR, 0.70 [95% CI, 0.52–0.95]), with reductions mainly in ischemic stroke (HR, 0.53 [95% CI, 0.37–0.78]) but did not significantly affect hemorrhagic (HR, 1.22 [95% CI, 0.59–2.54]) or strokes of undetermined origin (HR, 1.29 [95% CI, 0.57–2.95]). The combination of both interventions compared with double placebo substantially and significantly reduced strokes (HR, 0.56 [95% CI, 0.36–0.87]) and ischemic strokes (HR, 0.41 [95% CI, 0.23–0.72]). Among people at intermediate cardiovascular risk but without overt cardiovascular disease, rosuvastatin 10 mg daily significantly reduced first stroke. Blood pressure lowering combined with rosuvastatin reduced ischemic stroke by 59%. Both therapies are safe and generally well tolerated. URL: https://www.clinicaltrials.gov; Unique identifier: NCT00468923.

Lowering cholesterol, blood pressure, or both to prevent cardiovascular events: results of 8.7 years of follow-up of Heart Outcomes Evaluation Prevention (HOPE)-3 study participants.

AimsRosuvastatin (10 mg per day) compared with placebo reduced major adverse cardiovascular (CV) events by 24% in 12 705 participants at intermediate CV risk after 5.6 years. There was no benefit of blood pressure (BP) lowering treatment in the overall group, but a reduction in events in the third of participants with elevated systolic BP. After cessation of all the trial medications, we examined whether the benefits observed during the active treatment phase were sustained, enhanced, or attenuated.Methods and resultsAfter the randomized treatment period (5.6 years), participants were invited to participate in 3.1 further years of observation (total 8.7 years). The first co-primary outcome for the entire length of follow-up was the composite of myocardial infarction, stroke, or CV death [major adverse cardiovascular event (MACE)-1], and the second was MACE-1 plus resuscitated cardiac arrest, heart failure, or coronary revascularization (MACE-2). In total, 9326 (78%) of 11 994 surviving Heart Outcomes Prevention Evaluation (HOPE)-3 subjects consented to participate in extended follow-up. During 3.1 years of post-trial observation (total follow-up of 8.7 years), participants originally randomized to rosuvastatin compared with placebo had a 20% additional reduction in MACE-1 [95% confidence interval (CI), 0.64–0.99] and a 17% additional reduction in MACE-2 (95% CI 0.68–1.01). Therefore, over the 8.7 years of follow-up, there was a 21% reduction in MACE-1 (95% CI 0.69–0.90, P = 0.005) and 21% reduction in MACE-2 (95% CI 0.69–0.89, P = 0.002). There was no benefit of BP lowering in the overall study either during the active or post-trial observation period, however, a 24% reduction in MACE-1 was observed over 8.7 years.ConclusionThe CV benefits of rosuvastatin, and BP lowering in those with elevated systolic BP, compared with placebo continue to accrue for at least 3 years after cessation of randomized treatment in individuals without cardiovascular disease indicating a legacy effect.Trial Registration NumberNCT00468923

A novel method for interpreting survival analysis data: description and test on three major clinical trials on cardiovascular prevention

BackgroundMajor results of randomized clinical trials on cardiovascular prevention are currently provided in terms of relative or absolute risk reductions, including also the number needed to treat (NNT), incorrectly implying that a treatment might prevent the occurrence of the outcome/s under investigation. Provided that these results are based on survival analysis, the primary measure of which is time-to-the outcome and not the outcome itself, we sought an alternative method to describe, analyse and interpret clinical trial results consistent with this assumption, so as to better define qualitative and quantitative heterogeneity of various therapeutic strategies in terms of their effects and costs.MethodsThe original Kaplan-Meier graphs of three major positive cardiovascular prevention trials (PROVE-IT, LIFE and HOPE) were captured from the PDF images of the article and then digitalized. We calculated the difference between the placebo and active treatment curves and plotted it as a function of time to describe the event-free time gain (Time-Gain) produced by the active treatment. By calculating the exposure to the active treatment in terms of months (MoT) as a function of time and dividing it for the corresponding time-dependent number of event-free years gained (i.e. months/12), we described the kinetics of the pharmaco-economic index MoT/y+. The same procedure was repeated replacing MoT with the actual number of patients being treated at each time point as a function of time to obtain the NNT to gain 1 event-free year (NNT/y+) curve.ResultsThe Time-Gain curves depict the kinetics of the treatment-related effect over time and possess the peculiar feature of being smooth and accurately fitted by second-order polynomial functions (a*time2 + b*time); similarly, also the MoT/y+ and NNT/y+ curves can be accurately fitted by power functions (a*timeb).These curves and indices allow to fully appreciate the quantitative and qualitative heterogeneity, both in terms of effects and costs, of the different therapeutic strategies adopted in the three trials.ConclusionsWith our novel method, by exploiting original Kaplan-Meier curves from three major clinical trials on cardiovascular prevention, we generate new information on the actual consequences of choosing a therapeutic strategy vs another, thus ultimately providing the clinical gain in terms of time-dependent functions. Accurately assessing clinically and economic meaningful results from any intervention trial reporting positive results through this approach, facilitates objective comparisons and increases reliability in predicting survival among the various therapeutic options provided.Trial registrationPROVE-IT (Pravastatin or Atorvastatin Evaluation and Infection Therapy (TIMI22), Clinical trial registration number: NCT00382460, date of registration: September 29, 2006, study start date: November 2000).LIFE (Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) Study, Clinical trial registration number: NCT00338260, date of registration: June 20, 2006, study start date: June 1995).HOPE (Heart Outcomes Prevention Evaluation; we could not find Clinical trial registration number and date of registration).

Journal Digest

Journal Digest

Statin Use in Primary Prevention: A Simple Trial-Based Approach Compared With Guideline-Recommended Risk Algorithms for Selection of Eligible Patients

BackgroundCardiovascular disease risk assessment tools help identify individuals likely to benefit from preventative therapies. In this study we compared outcomes using the American College of Cardiology/American Heart Association (ACC/AHA) risk algorithm and the Framingham Risk Score (FRS) tool in the Heart Outcomes Prevention Evaluation (HOPE)-3 study. MethodsWe compared outcomes using the ACC/AHA algorithm and the FRS with those seen in HOPE-3, which randomized participants to 10 mg rosuvastatin or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; second coprimary outcome additionally included heart failure, cardiac arrest, and revascularization. ResultsRelative risks using risk scores were similar to those observed in the HOPE-3. Hazards ratios for the first coprimary outcome according to risk categories of ≤ 10%, 10%-20%, and ≥ 20% using the ACC/AHA algorithm were 0.82 (95% confidence interval [CI], 0.53-1.28), 0.72 (95% CI, 0.53-0.96), and 0.72 (95% CI, 0.55-0.93), and absolute risk reduction (ARR) of 0.18%, 1.33%, and 1.85%, respectively, over a median of 5.6 years. Corresponding results using the FRS were 0.69 (95% CI, 0.36-1.35), 0.73 (95% CI, 0.52-1.01), and 0.75 (95% CI, 0.60- 0.94); and ARR of 1.32%, 0.61%, and 1.43%. Hazard ratios for the second coprimary outcome were 0.77 (95% CI, 0.51-1.14), 0.73 (95% CI, 0.56-0.95), and 0.74 (95% CI, 0.58-0.94); and ARR of 0.36%, 1.49%, and 1.85%, using the ACC/AHA algorithm and 0.76 (95% CI, 0.41-1.41), 0.70 (95% CI, 0.52-0.95), and 0.76 (95% CI, 0.62-0.94); and ARR of 1.08%, 0.83%, and 1.56% using the FRS. ConclusionsThe pragmatic HOPE-3 trial approach identifies in an ethnically diverse primary prevention population individuals at intermediate risk who benefit from statin therapy using simple clinical characteristics without the need for complex, currently used risk assessment tools.

Effects of blood pressure and lipid lowering on cognition: Results from the HOPE-3 study.

To assess whether long-term treatment with candesartan/hydrochlorothiazide, rosuvastatin, or their combination can slow cognitive decline in older people at intermediate cardiovascular risk. The Heart Outcomes Prevention Evaluation-3 (HOPE-3) study was a double-blind, randomized, placebo-controlled clinical trial using a 2 × 2 factorial design. Participants without known cardiovascular disease or need for treatment were randomized to candesartan (16 mg) plus hydrochlorothiazide (12.5 mg) or placebo and to rosuvastatin (10 mg) or placebo. Participants who were ≥70 years of age completed the Digit Symbol Substitution Test (DSST), the modified Montreal Cognitive Assessment, and the Trail Making Test Part B at baseline and study end. Cognitive assessments were completed by 2,361 participants from 228 centers in 21 countries. Compared with placebo, candesartan/hydrochlorothiazide reduced systolic blood pressure by 6.0 mm Hg, and rosuvastatin reduced low-density lipoprotein cholesterol by 24.8 mg/dL. Participants were followed up for 5.7 years (median), and 1,626 completed both baseline and study-end assessments. Mean participant age was 74 years (SD ±3.5 years); 59% were women; 45% had hypertension; and 24% had ≥12 years of education. The mean difference in change in DSST scores was -0.91 (95% confidence interval [CI] -2.25 to 0.42) for candesartan/hydrochlorothiazide compared with placebo, -0.54 (95% CI -1.88 to 0.80) for rosuvastatin compared with placebo, and -1.43 (95% CI -3.37 to 0.50) for combination therapy vs double placebo. No significant differences were found for other measures. Long-term blood pressure lowering with candesartan plus hydrochlorothiazide, rosuvastatin, or their combination did not significantly affect cognitive decline in older people. NCT00468923. This study provides Class II evidence that for older people, candesartan plus hydrochlorothiazide, rosuvastatin, or their combination does not significantly affect cognitive decline.

Effects of Lipid-Lowering and Antihypertensive Treatments in Addition to Healthy Lifestyles in Primary Prevention: An Analysis of the HOPE-3 Trial.

BackgroundIt is not clear whether the effects of lipid‐lowering or antihypertensive medications are influenced by adherence to healthy lifestyle factors. We assessed the effects of both drug interventions in subgroups by the number of healthy lifestyle factors in participants in the HOPE‐3 (Heart Outcomes Prevention Evaluation) trial.Methods and ResultsIn this primary prevention trial, 4 healthy lifestyle factors (nonsmoking status, physical activity, optimal body weight, and healthy diet) were recorded in 12 521 participants who were at intermediate risk of cardiovascular disease (CVD) and were randomized to rosuvastatin, candesartan/hydrochlorothiazide, their combination, or matched placebos. Median follow‐up was 5.6 years. The outcome was a composite of CVD events. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models. Participants with ≥2 healthy lifestyle factors had a lower rate of CVD compared with those with fewer factors (HR: 0.85; 95% CI, 0.73–1.00). Rosuvastatin reduced CVD events in participants with ≥2 healthy lifestyle factors (HR: 0.74; 95% CI, 0.62–0.90) and in participants with <2 factors (HR: 0.79; 95% CI, 0.61–1.01). Consistent results were observed with combination therapy (≥2 factors: HR: 0.74; 95% CI, 0.57–0.97; <2 factors: HR: 0.61; 95% CI, 0.43–0.88). Candesartan/hydrochlorothiazide tends to reduce CVD only in participants with <2 healthy lifestyle factors (HR: 0.78; 95% CI, 0.61–1.00).ConclusionsHealthy lifestyles are associated with lower CVD. Rosuvastatin alone and combined with candesartan/hydrochlorothiazide is beneficial regardless of healthy lifestyle status; however, the benefit of antihypertensive treatment appears to be limited to patients with less healthy lifestyles.Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00239681.

Invited commentary

This report represents a thorough analysis of the search for associations between plasma renin or aldosterone levels and excised carotid artery plaque characteristics and composition and includes evaluation of many important intraplaque inflammatory mediators. Because activation of the renin-angiotensin system has been previously described to be associated with an increase in coronary and cerebrovascular events, it seemed logical to assume that these levels should correlate with the atherosclerotic plaque. Failure to find such a relationship was unexpected, which implies that the mechanism for the clinical outcomes is unrelated to acceleration of plaque lesion growth or plaque destabilization. Interestingly, a higher incidence of the composite of subsequent major clinical cardiovascular events was noted to be associated with higher levels of renin and aldosterone, although a history of prior cardiac disease at baseline was also higher among these patients. Nonetheless, the association of subsequent cardiovascular events did reflect greater numbers of adverse cerebrovascular and peripheral vascular episodes in addition to cardiac events. In attempting to understand the findings presented, it must be noted that plasma samples were obtained at only one point during the lifetime of the atherosclerotic process. Were the mature plaques derived from arteries that may have long since become activated by the renin-angiotensin system and no longer were dependent on it for continued activity, with the effect of renin and aldosterone most critical in the early stages of lesion development? Alternatively, although exclusion of patients using angiotensin-converting enzyme inhibitors in this real-life population would have severely limited the sample set size available for analysis, such inhibition may still compromise the ability to interpret these results, even if use of this drug class did not appear to affect the results of preliminary Cox regression analysis. Certainly, use of these inhibitors has been associated with reductions in cardiovascular events.1Yusuf S. Sleight P. Pogue J. Bosch J. Davies R. Dagenais G. Heart Outcomes Prevention Evaluation Study InvestigatorsEffects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients.N Engl J Med. 2000; 342: 145-153Crossref PubMed Scopus (8167) Google Scholar Could it be that elevated renin and aldosterone levels have, in fact, no causal role, but rather serve merely as markers of an as yet undiscovered mechanism of plaque destabilization? Whatever the case, atherosclerosis remains a complex process, resistant to complete explanation despite the laudable efforts of committed researchers such as Dr Hillaert and her colleagues. The opinions or views expressed in this commentary are those of the authors and do not necessarily reflect the opinions or recommendations of the Journal of Vascular Surgery or the Society for Vascular Surgery. Renin and aldosterone are not associated with vulnerable plaque characteristics in patients with carotid artery diseaseJournal of Vascular SurgeryVol. 68Issue 1PreviewThe renin-angiotensin-aldosterone system is increasingly being recognized to play an important role in the development and clinical course of cardiovascular diseases. Renin-angiotensin-aldosterone system activation is associated with clinical outcome in various populations of cardiovascular patients, such as patients with coronary artery, peripheral artery, and cerebrovascular disease. In this study, we investigated the associations between plasma renin and aldosterone concentrations and atherosclerotic plaque characteristics and secondary vascular events in patients undergoing carotid endarterectomy. Full-Text PDF Open Archive

Combined antihypertensive and statin therapy for the prevention of cardiovascular events in patients with hypertension without complications: protocol for a systematic review and meta-analysis

IntroductionHigh blood pressure (BP) affects over 40% of adults over the age of 25 worldwide and is the leading global risk factor for death or disability. Hypertension is also the...

Blood pressure and kidney update 2016/2017

The most important studies – from randomized controlled trials to perspective studies and meta-analyses, and guidelines in the topics of blood pressure and kidney research published in 2016 (and at the beginning of 2017) were reviewed. In the blood pressure area, the most important were the Systolic Blood Pressure Intervention Trial (SPRINT), which might have a great impact on the clinical practice as well as on the forthcoming guidelines, including the US recommendations recently published. Similarly important was the Heart Outcomes Prevention Evaluation (HOPE)-3 trial, which clearly confirmed that only combination therapy with antihypertensive drugs and statins might be effective in prevention of cardiovascular outcomes in patients at high risk of cardiovascular disease events. The research on kidney diseases was very interesting and extensive in 2016, and we have tried to present the most important data from the following areas: glomerulopathies, diabetic nephropathy, lupus nephritis, acute kidney injury, chronic kidney disease – risk factors, management and complications, and hemodialysis.

Patient at intermediate cardiovascular risk: statins, yes! - antihypertensive therapy, maybe.

Patient at intermediate cardiovascular risk: statins, yes! - antihypertensive therapy, maybe.

Abstract 104: First Stroke Reduced 44 Percent by Well Tolerated Medications. Stroke Outcomes From the Heart Outcomes Prevention Evaluation 3 Study

Background: Most (75%) strokes are first strokes, and primary prevention is crucial for reducing the global burden of stroke The role of fixed-dose antihypertensive therapy and statin drugs for primary stroke prevention has not been adequately defined. Methods: Using a 2x2 factorial design, 12,705 participants from 21 countries with an intermediate risk of cardiovascular disease but without overt vascular disease were randomized to fixed-dose candesartan 16 mg plus hydrochlorothiazide (HCTZ) 12.5 mg daily or placebo and to rosuvastatin 10mg daily or placebo. Results: Mean age was 66 years, 46% were women, and 166 strokes occurred during a median follow-up of 5.6 years. Mean baseline blood pressure (BP) was 138/82 mmHg and the BP difference between the treatment groups during follow-up averaged 6.0/3.0 mmHg. Stroke was reduced by 20% (confidence interval [CI], 0.59-1.08; p =0.14) by candesartan/HCTZ and 30% (CI, 0.52-0.95) by rosuvastatin. In a pre-specified subgroup analysis, participants in the upper third of systolic BP (&gt;143.5 mmHg) had stroke reduced by 42% (CI, 0.37-0.90, p =0.02). Rosuvatatin reduced all stroke by 30% (CI, 0.52-0.95; p =0.02); but considering hemorrhagic strokes: 15 among those assigned rosuvastatin vs. 12 with rosuvastatin-placebo. Those assigned both rosuvatatin and candesartan/HCTZ had stroke reduced by 44% ( CI, 0.36-0.87; p =0.009). Rates of permanent discontinuation did not differ significantly between active and placebo-assigned patients. Conclusions: Fixed-dose candesartan/HCTZ combined with low-dose rosuvastatin reduced first stroke by 44% in patients at intermediate risk of cardiovascular disease and was well-tolerated. Among those with systolic BP &gt;143.5 mmHg, fixed-dose candesartan/HCTZ reduces first stroke by 42%,

Long-term Effects of Statins, Blood Pressure-Lowering, and Both on Erectile Function in Persons at Intermediate Risk for Cardiovascular Disease: A Substudy of the Heart Outcomes Prevention Evaluation-3 (HOPE-3) Randomized Controlled Trial

BackgroundIt is unclear whether modifying cholesterol, blood pressure, or both affect erectile dysfunction. Also, there are concerns that erectile dysfunction is worsened by common medications used to treat these risk factors. In this study, we evaluated the effect of: (1) cholesterol-lowering with a statin; (2) pharmacologic blood pressure reduction; and (3) their combination, on erectile function. MethodsA priori, this was a secondary analysis of the Heart Outcomes Prevention Evaluation-3 (HOPE-3) randomized controlled trial. Men were 55 years of age or older with at least 1 cardiovascular risk factor. Erectile function was measured using the erectile function domain of the International Index of Erectile Function (IIEF-EF) score. Men with incomplete scores, or who did not engage in sexual activity, were excluded. Using a 2 × 2 factorial design, participants were randomized to rosuvastatin (10 mg/d) or placebo, and to candesartan with hydrochlorothiazide (HCTZ; 16 mg/12.5 mg/d; Cand+HCTZ) or placebo. Primary outcome was change in IIEF-EF from baseline to end of study follow-up. ResultsTwo thousand one hundred fifty-three men were included; mean age was 61.5 years, and mean follow-up was 5.8 years. Mean IIEF-EF score at baseline was 23.0 (SD 5.6). Least square mean change in the IIEF-EF score did not differ with rosuvastatin compared with placebo (−1.4; standard error [SE], 0.3 vs −1.5; SE, 0.3; P = 0.74), Cand+HCTZ compared with placebo (−1.6; SE, 0.3 vs −1.3; SE, 0.3; P = 0.10), or combination therapy compared with double placebo (P = 0.35). ConclusionsCholesterol-lowering using a statin, and blood pressure-lowering using Cand+HCTZ, either alone or in combination, do not improve or adversely affect erectile function.

Powerful diuretics: A common denominator in landmark hypertension and type 2 diabetes mellitus trials.

Powerful diuretics: A common denominator in landmark hypertension and type 2 diabetes mellitus trials.

Abstract 23084: Marked Global Variability in Cost Effectiveness of Lipid-Lowering and Combination Antihypertensive Therapies in Primary Prevention: Analyses of the HOPE-3 Trial

Background: The Heart Outcomes Prevention Evaluation (HOPE) - 3 trial demonstrated that low dose lipid-lowering medication alone or with an angiotensin receptor blocker (ARB)+ thiazide resulted in a significantly lower risk of cardiovascular events compared to placebo in intermediate risk persons without cardiovascular disease. Since use of these medications in primary prevention could have significant cost implication, we report the cost analysis of the HOPE-3 trial. Methods: Hospitalization events, procedures, medications and study drugs were extracted for each patient. We applied country-specific costs to healthcare resources consumed for each patient. We calculated average cost per patient for the length of the study (median follow-up 5.6 years). Costs are reported in US dollars and discounted at 3% per year. The costs of the study drugs vary considerably between countries and we use the most locally affordable (generic) lipid-lowering medication and ARB + diuretic combination. Results: In most regions, use of lipid-lowering medication in combination with antihypertensive drugs in HOPE-3 was cost-neutral or cost-saving as the cost of these medications was offset by savings in other costs (events, procedures, and usual medications). Surprisingly, in India and China, the cost of these medications is the main component of overall health expenditures, being more expensive than all other costs. Conclusions: The use of lipid-lowering medication alone or with antihypertensives agents is cost-saving in most regions by providing significant clinical benefit to intermediate risk persons without cardiovascular disease. Prices for these generic drugs in India and particularly in China are high relative to other costs and policies to reduce the prices of these are needed to ensure that generics are more affordable. Primary prevention using lipid-lowering medication and antihypertensive agents would be cost-neutral or cost-saving worldwide.

Treatment Targets in Hypertension

The optimal target blood pressure (BP) in the treatment of hypertensive patients remains controversial. Recently, the systolic blood pressure trial (SPRINT) has proposed that a target systolic blood pressure of < 120 mmHg provides prognostic benefit in elderly hypertensive patients at high cardiovascular risk. The results of SPRINT contrast with several other intervention trials which have investigated the effect of intense BP lowering (Secondary Prevention of Small Subcortical Strokes [SPS3], Action to Control Cardiovascular Risk in Diabetes [ACCORD], Heart Outcomes Prevention Evaluation [HOPE]-3). The differences in outcomes in SPRINT vs. other intervention trials are, to a large extend, due to an "unobserved" BP measurement procedure utilized in the SPRINT trial. Thus, a BP goal of < 120 mmHg, at least by conventional BP measurement, remains unproven. Independent of SPRINT the controversial evidence with respect to BP targets calls for further studies and, possibly, for more individualized treatment goals.

Validation of the ORIGIN Cardiovascular Biomarker Panel and the Value of Adding Troponin I in Dysglycemic People.

Analyses of stored blood from the Outcomes Reduction with an Initial Glargine Intervention (ORIGIN) trial identified biomarkers that supplemented clinical risk factors for cardiovascular (CV) events or death. Their performance in participants with diabetes in the Heart Outcomes Prevention Evaluation (HOPE) study and the incremental value of adding high-sensitivity assays of serum troponin I (hsTnI) in the ORIGIN study were assessed. Levels of the 10 ORIGIN biomarkers for the composite CV outcome of myocardial infarction, stroke, or CV death were measured in 350 HOPE study participants with diabetes and stored serum that included all 77 who experienced this outcome. The effect of adding hsTnI levels to this panel, and the previously identified ORIGIN biomarkers for this composite outcome, this outcome, or revascularization or heart failure, and for mortality was also analyzed. Within the HOPE cohort, the ORIGIN biomarker panel increased the C statistic from 0.63 for clinical risk factors alone to 0.67 with the addition of the 10 biomarkers, and the net reclassification improvement was 0.14 (95% confidence interval, 0.01, 0.28). Within the ORIGIN cohort, hsTnI levels predicted all three outcomes during follow-up both alone, and independently of the other biomarkers, which all remained independent predictors of outcomes after inclusion of the hsTnI levels. The hsTnI level interacted with follow-up time such that it was a stronger predictor of earlier vs later events. The ORIGIN biomarkers predicted CV outcomes in the independent HOPE cohort. Adding hsTnI levels to the previously identified models in ORIGIN modestly improved their performance.