Relative Risk Reduction In All-cause Mortality Research Articles

MP-453090-7 IDENTIFYING PATIENTS WITH LVEF≤55% WHO MAY BENEFIT FROM A PRIMARY PREVENTION ICD USING SEATTLE PROPORTIONAL RISK MODEL FOR MILDLY REDUCED EF (SPRM-MR) IN 14,752 PATIENTS

Patients with EF>30-35% remain at risk of sudden cardiac death (SCD) but are not currently indicated for a primary prevention ICD. Previous research has identified greater ICD benefit in those with a higher proportion of SCD. We sought to identify patients with EF≤55% who have a high proportion of SCD who may benefit from an ICD. Patients with EF≤55% not eligible for an ICD (NYHA 1- NonIschemic EF 1-55%, Ischemic EF 31-55%, NYHA 2-4 EF 36-55%) with mode of death from clinical trials (Val-HeFT, IPreserve, HAT-AED, HEAAL, GISSI-HF) and prospective observational studies (PRE-DETERMINE, UW, and Italian HF Registry). A Cox Proportional all-cause mortality (ACM) model and logistic regression SCD proportional risk models (SPRM-MR) were derived. Patients were considered potential ICD candidates if the predicted proportion of SCD was ≥45% and the estimated sudden death rate at 5 years ≥5%. ICD benefit was estimated by applying the SPRM*ICD interaction for ACM in HFrEF patients in SCD-HeFT (https://depts.washington.edu/sprm). The cohort included 14,752 patients. During a median follow-up of 3.6±1.4 years, 2,296 (15.6%) died. SCD comprised 30.5% of known deaths. Younger age, male sex, lower EF, higher SBP, and lower creatinine were associated with a higher proportion of SCD. One in 4 patients (23%) had a predicted SCD proportion ≥45% (observed SCD proportion 53%). An estimated SCD 5-year rate of ≥5% was present in 54% of patients. The potential ICD cohort (SPRM-MR≥45% and SCD 5yr ≥5%) comprised 11% of the entire study population. This was 17% with EF ≤45% vs <1% with EF >45%. In the potential ICD cohort, the 5 year Kaplan Meier ACM was 16.8% with 52% sudden death (∼8.7% at 5 years) vs. 20.9% ACM with 28% sudden death in the remaining patients. The estimated ICD benefit was a relative risk reduction in ACM of 27% with an ∼5% absolute risk reduction in ACM at 5 years. The 5 year number needed to treat of 20. Nearly 1 in 5 patients with an LVEF ≤ 45% who do not meet contemporary guideline criteria for ICD implantation demonstrate significant absolute (≥5%/5 years) and proportional (≥45%) risks of SCD. In these patients, we estimate an ICD would provide a 27% relative risk and 5% absolute risk reduction in all-cause mortality with a number needed to treat to save one life with an ICD of 20. Future efforts should focus on the use of integrating absolute and proportional risk as inclusion criteria for evaluating ICD benefit in this substantial population.

Primary Prevention of Major Cardiovascular and Cerebrovascular Events with Statins in Diabetic Patients

Patients with diabetes mellitus are at increased risk of developing cardiovascular disease. Controlling lipid levels has a preventive effect on the occurrence of major cardiovascular and cerebrovascular events. Individual trials have shown varying data on the efficacy of treatment with lipid-lowering statin therapy in the primary prevention of such events in diabetes. The objective of this study was to assess the efficacy of statins in the primary prevention of the first-time occurrence of a major cardiovascular or cerebrovascular event in diabetic patients. Secondary endpoints were fatal/non-fatal stroke, fatal/non-fatal myocardial infarction and all-cause mortality. A systematic search for trial reports was conducted in PubMed, EMBASE, The Cochrane library and clinicaltrials.gov for the years 1966-2011. Reference lists of reviews and meta-analyses of related subjects were searched. High-quality, randomized, double-blinded clinical trials comparing a statin with placebo for the primary prevention of major cardiovascular and cerebrovascular events in diabetic patients were selected. Only large studies with a minimum of 500 diabetic participants followed-up for at least 2 years were included. Endpoints were major cardiovascular and cerebrovascular events. Trial and patient characteristics were extracted by three researchers. The quality of the included studies was tested with the Jadad score. The combined effect on primary as well as secondary endpoints was measured with a fixed-effect model. Publication bias was examined with a funnel plot. Four trials were included, for a total of 10,187 participants. Treatment with statins in the primary prevention of major cardiovascular and cerebrovascular events in diabetic patients resulted in a significant relative risk (RR) reduction in the first-time occurrence of major cardiovascular or cerebrovascular events (RR 0.75, 95% CI 0.67-0.85), fatal/non-fatal stroke (RR 0.69, 95% CI 0.51-0.92) and fatal/non-fatal myocardial infarction (RR 0.70, 95% CI 0.54-0.90) and a non-significant RR reduction in all-cause mortality (RR 0.84, 95% CI 0.65-1.09). Among the studies there was non-significant heterogeneity in the individual effect estimates and no publication bias. Exclusion criteria and endpoints varied slightly between studies. The type and dosing of statin therapy differed between studies. Non-compliance in the statin treatment group and the use of statin treatment in the placebo group could have led to lower risk reductions. Treatment with statins in primary prevention among diabetic patients has a significant beneficial effect on event rates of the first-time occurrence of a major cardiovascular or cerebrovascular event, fatal/non-fatal stroke and fatal/non-fatal myocardial infarction. There was a non-significant RR reduction in all-cause mortality.