M 26: Do Drugs Interact Together in Cardiovascular Prevention? A Meta-Analysis of Powerful Randomized Controlled Trials
PhD Student, Service of Clinical Pharmacology, EMET/FMPO
University Cheikh Anta Diop/Université Claude Bernard Lyon1, France Senegal
Preventive cardiovascular drugs (antihypertensive, antiplatelet, lipid lowering and antidiabetic agents) are frequently co-prescribed to treat patients. Whether these treatments interact together has never been evaluated. We explored here their interactions in terms of cardiovascular risk reduction.
We analyzed powerful randomized controlled trials (>1000 patients) and explored heterogeneity between co-prescribed drugs and diabetes/hypertension to measure interaction (significant if p>0.10 and I²>50%). We illustrated the extent to which potentially significant interaction could be eliminated.
We explored the changes of drug effects of the four classes (anti-aggregant platelet agents-APA, antihypertensive agents-AHA, oral antidiabetic agents- ODA and statin), according to cross-exposure between them and with the hypertension and diabetes status. Comparisons of major coronary events and major vascular events between sub-group treatments were expressed by the pooled Relative Risk (RR) with 95% Confidence Intervals (CI).
In total, 19 RCTs were selected in our meta-analysis, which enrolled a total of 210 865 patients (106 563 for treatment/intensive treatment arm and 104 302 for placebo/standard treatment arm). The follow-up durations ranged between 2.1-10 years. The quality of the studies included was relatively high: 100% low risk for selection, performance and attrition biases, 90% low risk for detection bias, >85% low risk for reporting bias and about 80% for other bias.
Eight trials assessed the effect of statin (n= 58100 patients), two with APA (n= 58 666 patients), five with AHA (n = 40 329 patients) and five with ODA (n= 53 770 patients) versus placebo, except two trials which compared the effect of the same treatments but of different intensifications. Thirteen trials allowed examining the interactions between drugs used and hypertension and 10 trials allowed examining the interactions between drugs and diabetes status
The relative risks associated with these treatments ranged from 0.71 [0.58, 0.88] to 0.96 [0.90, 1.02] with statistical significances. No any significant interaction between co-prescribed medications or between prescribed medication and diabetes and hypertension status was observed in our study (p= 0.79, I²= 0%). The lack of significant interaction did not eliminate all the possibilities of such treatment combinations. However, our results allowed eliminating treatment changes above 50% of the relative benefit for all interactions, and above 20% for the benefit of statin in hypertension.
Our study is the first one exploring the interaction between preventive cardiovascular drugs and with risk factors (hypertension/diabetes) in primary and secondary cardiovascular prevention, using data from the most powerful randomized controlled trials. This meta-analysis demonstrates that combining antihypertensive drugs, antiplatelet agents, statin and antidiabetics agents could be effective and safe for major vascular and coronary prevention in high risk patients. It also demonstrated that there were no interactions observed between the co-prescribed drugs and between these medications and diabetes/hypertensions status.