Prediction of absolute risk reduction of cardiovascular events with perindopril for individual patients with stable coronary artery disease — Results from EUROPA

Leeuw, Joep van der; Oemrawsingh, Rohit M.; Graaf, Yolanda van der; Brugts, Jasper J.; Deckers, Jaap W.; Bertrand, Michel E.; Fox, Kim; Ferrari, Roberto; Remme, Willem J.; Simoons, Maarten L.; Boersma, Eric; Visseren, Frank L.J.

doi:10.1016/j.ijcard.2014.12.046

Cited by 11 publications

(7 citation statements)

References 35 publications

(33 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…34,35 These papers join a growing list of papers showing clinically important variation in benefits when trial results are risk stratified, typically showing that an identifiable subgroup of higher-risk patients often account for most of the treatment benefit. [36][37][38][39][40][41][42][43][44][45][46] Another consistent finding was that the median predicted outcome risk in these trials was lower than the mean predicted risk (i.e. MMRR < 1).…”

Section: Discussionmentioning

confidence: 86%

“…Whereas several trials in our database of trials exhibited large heterogeneity in predicted outcome risk, overall the results of our analyses were somewhat less extreme than previous published examples might have suggested. [36][37][38][39][40][41][42][43][44][45] There are several explanations for this observation. First, risk heterogeneity may be somewhat restricted in large phase III randomized studies if they tend to enroll homogeneous patient populations.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Risk and treatment effect heterogeneity: re-analysis of individual participant data from 32 large clinical trials

et al. 2016

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Risk and treatment effect heterogeneity: re-analysis of individual participant data from 32 large clinical trials

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Although these data show a benefit from the use of ACE inhibitors in the treatment of heart disease, the residual risk of events (1.0 minus RR) documented in these studies is close to or greater than 70%. Additional studies from well-conducted clinical trials shows that the "residual risk" for cardiovascular events is substan-tially greater than the risk reduction achieved by these agents (1,12,18,36,60,75,132,133,(145)(146)(147).…”

Section: H409mentioning

confidence: 99%

Intracrine angiotensin II functions originate from noncanonical pathways in the human heart

Ferrario

Ahmad

Varagić

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Although it is well-known that excess renin angiotensin system (RAS) activity contributes to the pathophysiology of cardiac and vascular disease, tissue-based expression of RAS genes has given rise to the possibility that intracellularly produced angiotensin II (Ang II) may be a critical contributor to disease processes. An extended form of angiotensin I (Ang I), the dodecapeptide angiotensin-(1-12) [Ang-(1-12)], that generates Ang II directly from chymase, particularly in the human heart, reinforces the possibility that an alternative noncanonical renin independent pathway for Ang II formation may be important in explaining the mechanisms by which the hormone contributes to adverse cardiac and vascular remodeling. This review summarizes the work that has been done in evaluating the functional significance of Ang-(1-12) and how this substrate generated from angiotensinogen by a yet to be identified enzyme enhances knowledge about Ang II pathological actions.

show abstract

“…37 For preventive therapies that are associated with considerably higher NNTs, such as blood-pressure-lowering therapy (5-year NNTs between 80 and 160, 37 corresponding with 10-year NNTs between 40 and 80), previous studies have shown that applying a prediction model may similarly result in higher net benefit compared with a strategy in which all patients are treated. 38,39 Importantly, in patients at relatively high risk of cardiovascular events, the net benefit of a prediction-based treatment strategy will be comparable to a strategy in which all patients are treated because high-risk patients are likely to exceed the treatment threshold and therefore all will be treated in both scenarios. Therefore, the additional value of a predictionbased strategy lies in selective treatment of patients in the lower risk groups (not exceeding the treatment threshold).…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of a Model to Predict Absolute Vascular Risk Reduction by Moderate-Intensity Statin Therapy in Individual Patients With Type 2 Diabetes Mellitus

Kaasenbrood

Poulter

Sever

et al. 2016

Circ: Cardiovascular Quality and Outcomes

Self Cite

View full text Add to dashboard Cite

Statin therapy is effective in preventing major cardiovascular events in patients with type 2 diabetes mellitus with an average relative risk reduction that is similar to the effect of statins in patients without type 2 diabetes mellitus.1 Based on this, guidelines recommend statin therapy for most patients with type 2 diabetes mellitus. 2,3 In clinical practice, decisionBackground-In this study, we aimed to translate the average relative effect of statin therapy from trial data to the individual patient with type 2 diabetes mellitus by developing and validating a model to predict individualized absolute risk reductions (ARR) of cardiovascular events. Methods and Results-Data of 2725 patients with type 2 diabetes mellitus from the Lipid Lowering Arm of the AngloScandinavian Cardiac Outcomes Trial (ASCOT-LLA) study (atorvastatin 10 mg versus placebo) were used for model derivation. The model was based on 8 clinical predictors including treatment allocation (statin/placebo). Ten-year individualized ARR on major cardiovascular events by statin therapy were calculated for each patient by subtracting the estimated on-treatment risk from the estimated off-treatment risk. Predicted 10-year ARR by statin therapy was <2% for 13% of the patients. About 30% had an ARR of >4% (median ARR, 3.2%; interquartile range, 2.5%-4.3%; 95% confidence interval for 3.2% ARR, -1.4% to 6.8%). Addition of treatment interactions did not improve model performance. Therefore, the wide distribution in ARR was a consequence of the underlying distribution in cardiovascular risk enrolled in these trials. External validation of the model was performed in data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT; pravastatin 40 mg versus usual care) and Collaborative Atorvastatin Diabetes Study (CARDS; atorvastatin 10 mg versus placebo) of 3878 and 2838 patients with type 2 diabetes mellitus, respectively. Model calibration was adequate in both external data sets, discrimination was moderate 0.64 [95% confidence interval,

show abstract

Prediction of absolute risk reduction of cardiovascular events with perindopril for individual patients with stable coronary artery disease — Results from EUROPA

Abstract: ISRCTN37166280.

Cited by 11 publications

References 35 publications

Risk and treatment effect heterogeneity: re-analysis of individual participant data from 32 large clinical trials

Risk and treatment effect heterogeneity: re-analysis of individual participant data from 32 large clinical trials

Intracrine angiotensin II functions originate from noncanonical pathways in the human heart

Development and Validation of a Model to Predict Absolute Vascular Risk Reduction by Moderate-Intensity Statin Therapy in Individual Patients With Type 2 Diabetes Mellitus

Contact Info

Product

Resources

About