Differences in Primary Outcome in Diabetic and Non-Diabetic Patients; Meta-Analysis of Randomized Controlled Trials of Statin Therapy for Primary Cardiovascular Prevention - The 65th Annual Conference of the Israel Heart Society & The Israel Society of Cardiothoracic Surgery, 24-25 April 2018

Roman Nevzorov ICCU, Barzilai University Medical Center, Ashqelon, Israel Elinor Briskin Clalit Health Service, Dan Petach-Tikva Region, Israel Yoav Arnson Division of Cardiology, Meir Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Kfar Saba, Israel David Pereg Division of Cardiology, Meir Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Kfar Saba, Israel Itamar Raz Center for Prevention of Diabetes and Diabetes Clinical Research Center, Hadassah Hebrew University Medical Center, Jerusalem, Israel Morris Mosseri Division of Cardiology, Meir Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Kfar Saba, Israel

Background: Diabetes mellitus type 2 is a prominent risk factor for cardiovascular disease (CVD). Diabetic patients have an increased risk for CVD and worse prognosis compared to non-diabetics persons. Reducing cardiovascular (CV) risk in diabetic patients requires global treatment of other risk factors such as hypercholesterolemia. Statins reduce total and LDL cholesterol levels and improve prognosis in the general population as well as in diabetic patients. However, it is not clear whether statin therapy in diabetic patients is as effective as in non-diabetics.

Purpose: To compare the effect of statins for primary prevention between diabetic and non-diabetic persons.

Methods: The PubMed was searched for randomized controlled trials of statins for primary prevention during the past 20 years. Included were trials that studied statins therapy vs. placebo or usual care in at least 500 individuals for a minimum of one year. Primary outcome in the trials was mortality or composite cardiovascular outcome that incorporated mortality. We conducted a meta-analysis aimed at the difference in primary outcome between the diabetic and non-diabetic patients.

Results: Eleven trials fulfilling our inclusion criteria were found. These 11 studies enrolled a total of 74,902 patients, 10,412 (13.9%) of whom were diabetic. Statins studied in these studies were lovastatin, fluvastatin, pravastatin, simvastatin, atorvastatin and rosuvastatin. Pooled analysis revealed 20.2% reduction in primary outcome in non-diabetic patients (Odds ratio [OR] 0.79, 95% CI 0.76-0.83; p < 0.001) and 15.3% reduction in primary outcome in diabetic patients ([OR] 0.84, 95% CI 0.77-0.93; p< 0.001). Combined analysis of only 8 RCTs with positive results (that exhibited significant reduction of primary end-point) revealed 25% reduction in primary outcome in non-diabetic patients ([OR] 0.75, 95% CI 0.71-0.79, p< 0.001) and 20.7% reduction in diabetic patients ([OR] 0.79, 95% CI 0.70-0.89, p<0.001). Â Testing for a statistical difference between the two odds ratio estimates of meta-analyses in diabetic and non-diabetic groups determined that the reduction of primary end-point wasn`t statistically different (the confidence intervals overlap) both in all enrolled trials (p =0.66) and in "positive" trials (p=0.56).Â

Conclusion: This meta-analysis of RCTs of statins for primary prevention shows a favorable effect in reduction of primary outcome both in diabetic and in non-diabetic patients with no statistically significant difference. However, it is not clear whether statin therapy restores CV risk in diabetic patients to that in the general population.