New insights into predictors of new onset diabetes among hypertensive patients are revealed in the ASCOT study trial , announced in the clinical trial update I session today. The study reveals fasting plasma glucose , body mass index index, HDL and triglyceride levels and the type of antihypertensive therapy prescribed all provide potential baseline predictors for developing diabetes. Here presenter Ajay K Gupta (Imperial College, London) and discussant J L Zamorano Gomez (Madrid, Spain) provide an overview of the results.
Introduction
Controversy persists regarding the influence of the beta-blockers and/or diuretics on the development of new onset diabetes (NOD). In-addition, there is a paucity of data regarding other predictors of diabetes in hypertensive patients.
Objectives
To determine the baseline predictors of NOD in hypertensive patients, and to develop a risk score to identify those at high risk of NOD.
Materials and Methods
Among 19342 patients in ASCOT-BPLA, 14120 (mean age 62.8 yrs) were not diabetic at baseline. Of these, 1366 (9.7%) subsequently developed NOD during median follow-up of 5.5years. A multivariate Cox proportional hazard model was developed to identify the independent predictors of NOD, and individual risk scores.
Results
NOD was significantly associated with increase in baseline fasting plasma glucose (FPG), body mass index, serum triglyceride and systolic blood pressure. In contrast, amlodipine ± perindopril in comparison with atenolol ± thiazide treatment (HR 0.66 95%CI 0.59-0.74), high HDLc, alcohol use and age >55 were found to be significantly protective factors. FPG was the most powerful predictor with risk increasing by 5.8 times (95%CI 5.23-6.43) for each mmol/l rise above 5 mmol/l. Risk of NOD increased steadily with increasing quartile of risk score, with a nineteen-fold increase (95% CI 14.3-25.4) among those in the highest compared with those in the lowest quartile. The model showed excellent internal validity and discriminative ability.
Conclusions
Baseline FPG >5mmol/l and use of an atenolol- based regimen were among the major determinants of NOD.
Clinical implications
The current analysis shows the importance of antihypertensive therapy particularly the relative adverse effect of combination of beta-blockers ± thiazide as an independent predictor of NOD. Further, it describes a robust, discriminative model, which may be useful to predict the risk of NOD in hypertensive patients and can potentially influence the prescribing practices of clinicians.
Slide presentation [Available]
New insights into predictors of new onset diabetes among hypertensive patients are revealed in the ASCOT study trial , announced in the clinical trial update I session today. The study reveals fasting plasma glucose , body mass index index, HDL and triglyceride levels and the type of antihypertensive therapy prescribed all provide potential baseline predictors for developing diabetes. Here presenter Ajay K Gupta (Imperial College, London) and discussant J L Zamorano Gomez (Madrid, Spain) provide an overview of the results.
Introduction
Controversy persists regarding the influence of the beta-blockers and/or diuretics on the development of new onset diabetes (NOD). In-addition, there is a paucity of data regarding other predictors of diabetes in hypertensive patients.
Objectives
To determine the baseline predictors of NOD in hypertensive patients, and to develop a risk score to identify those at high risk of NOD.
Materials and Methods
Among 19342 patients in ASCOT-BPLA, 14120 (mean age 62.8 yrs) were not diabetic at baseline. Of these, 1366 (9.7%) subsequently developed NOD during median follow-up of 5.5years. A multivariate Cox proportional hazard model was developed to identify the independent predictors of NOD, and individual risk scores.
Results
NOD was significantly associated with increase in baseline fasting plasma glucose (FPG), body mass index, serum triglyceride and systolic blood pressure. In contrast, amlodipine ± perindopril in comparison with atenolol ± thiazide treatment (HR 0.66 95%CI 0.59-0.74), high HDLc, alcohol use and age >55 were found to be significantly protective factors. FPG was the most powerful predictor with risk increasing by 5.8 times (95%CI 5.23-6.43) for each mmol/l rise above 5 mmol/l. Risk of NOD increased steadily with increasing quartile of risk score, with a nineteen-fold increase (95% CI 14.3-25.4) among those in the highest compared with those in the lowest quartile. The model showed excellent internal validity and discriminative ability.
Conclusions
Baseline FPG >5mmol/l and use of an atenolol- based regimen were among the major determinants of NOD.
Clinical implications
The current analysis shows the importance of antihypertensive therapy particularly the relative adverse effect of combination of beta-blockers ± thiazide as an independent predictor of NOD. Further, it describes a robust, discriminative model, which may be useful to predict the risk of NOD in hypertensive patients and can potentially influence the prescribing practices of clinicians.
Slide presentation [Available] Session Number : 710005
Session Title: Clinical Trial Update I
Conclusion
DISCUSSANT: Zamorano Gomez, J.L.
Hypertension is a hallmark of Cardiovascular diseases.
We have learned from recent trials that the main discussion when choosing the adequate therapy for hypertensive patients is not deciding which specific agent should be used but moreover which specific combination will be better for an specific patient. With this in mind, the different patient profile is crucial in deciding the pharmacological strategy.
It seems to be clear that ACE-I & ARABs are first line therapy for diabetics with hypertension, not clearly recommended in this subgroup diuretics or beta blockers and neutral effect calcium channel antagonist. Diabetes clearly increase the risk of hypertensive patients. In the recent years, different trials have shown interest in demostrating the benefit of the different drugs in the development of new onset of diabetes (NOD). A couple of observational studies have suggested that NOD is not quite innocentACE-I, ARABs have shown to demonstrate a reduction of the risk in the development of new onset of diabetes.
In ASCOT 1366 patients developed diabetes the hazard ratio was 0.69 (95% CI 0.62-0.77, p<0001) for the amlodipine arm vs the atenolol arm.looking to the ASCOT trial and other previous trials, it seems that Amlodipine has neutral effect in such effect. Also we need to consider, as presented by Dr Gupta, that all of the 34% difference in the two treatment groups in the ASCOT trial cannot be due to ACE in amlodipine+/-perindopril group, simply because not all received perindopril, and secondly this difference is much more than 20% which is being suggested in metanalysis on ACE/ARB's, where all received ACE/ARB's.
Consequently, certain proportion of the final effect must also lies on the atenolol+/- thiazide group particularly atenolol. In most of the trials, the development of new onset of diabetes was not followed by clinical events, probably due to the ack of really long term follow up. The new interesting data provided by DrGupta in the Ascot trial is the possibility of calculating the risk of development of new onset of diabetes in an specific patient. Looking at the patient characteristics the strongest baseline predictors were fasting blood sugar levels, BMI, triglycerides and antihypertensive drug, while HDL had a protective effect. Combining the 11 most important risk factors for NOD it was possible to calculate a risk score which was extremely good at discriminating between risk groups presented in quartiles.
This is very promising. However, such a score needs to be validated in another population. With this in mind, it is not difficult to think that this calculation could be also used in order to select which drug (or combination) could be the better choice for an specific patient. This could be considered as other clinical features in the final decision of which strategy should be used for different patients.
