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Objective: To estimate the average outcome postponement (gain in days to an event) for cardiovascular outcomes in a meta‐analysis of randomized, controlled statin trials, including any myocardial infarction, any stroke and cardiovascular death. Design: Systematic review of large randomized, placebo‐controlled trials of statin use, including a random‐effects meta‐analysis of all included trials. Data sources: We searched MEDLINE (15 July 2019) and ClinicalTrials.gov (16 October 2019). Eligibility criteria for selecting studies: Randomized, placebo‐controlled trials of statin use that included at least 1000 participants. We identified 15 cardiovascular outcomes that were reported in more than 2 trials. Results: We included 19 trials. The summary outcome postponements for the 15 cardiovascular outcomes varied between −1 and 38 days. For four major outcomes, the summary outcome postponement in days was as follows: cardiovascular mortality, 9.27 days (95% CI: 3.6 to 14.91; I2 = 72%; 9 trials) non‐vascular and non‐cardiovascular mortality, 1.5 days (95% CI: −2.2 to 5.3; I2 = 0%; 6 trials) any myocardial infarction 18.0 days (95% CI; 12.1 to 24.1; I2 = 92%; 15 trials); and any stroke, 6.1 days (95% CI; 2.86 to 9.39; I2 = 66%; 14 trials). Conclusion: Statin treatment provided a small, average postponement of cardiovascular outcomes during trial duration. [ABSTRACT FROM AUTHOR]

Background: Outcome postponement has been proposed as an effect measure for preventive drug treatment. It describes the average delay of the investigated unwanted clinical event, achieved by taking medication. The objective was to estimate postponement of death for the following heart failure medications compared to placebo: beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), ARB added to ACE inhibitors, aldosterone antagonists, ivabradine, and renin antagonists.Methods: We searched Medline and Embase from inception of databases until October 2017. Eligibility criteria were randomized placebo-controlled heart failure trials, including at least 1000 participants, with survival as a prespecified outcome and a minimum trial duration of 1 year. We calculated the outcome postponement by modeling the area between survival curves. This area was modeled on the basis of the hazard ratio or relative risk, the rate of mortality in the placebo group, and the trial duration. All results were standardized to a 3-year trial duration to ensure comparability between treatments.Results: We identified 14 eligible trials, with a total of 52,014 patients. The results in terms of postponement of all-cause mortality was: beta-blockers 43.7 days (95% confidence interval [95% CI], 20.8-66.5), ACE inhibitors 41.0 days (95% CI, 18.8-63.3), and aldosterone-antagonists 41.3 days (95% CI, 14.3,68.4).Conclusion: The modeled outcome postponement estimates reiterate beta-blockers, ACE inhibitors, and aldosterone antagonists as the mainstay of heart failure treatment. Furthermore, ivabradine or ARBs added to ACE inhibitors results in no statistically significant gain in survival. [ABSTRACT FROM AUTHOR]

Background: The impact of randomised controlled trials (RCTs) depends heavily on the presentation of the findings. Objective: Classically, RCT findings are presented in the form of absolute risk reduction (ARR), number needed to treat (NNT) to prevent one adverse outcome, and relative risk reduction (RRR) or hazard ratio (the most favourable means for drug marketing). However, the estimation of average survival gain (i.e. outcome postponement between a trial intervention and comparator) is an alternative and informative means of presenting the findings of RCTs. Study selection: Recent cardiovascular RCTs evaluating ezetimibe added to simvastatin, evolocumab, canakinumab, ticagrelor, rivaroxaban, ivabradine, LCZ 696 (sacubitril/valsartan), and transfemoral aortic valve replacement are analysed and discussed. Findings: The average survival gains ranged between 4.9 days on a composite end point with ticagrelor versus clopidogrel in randomised patients with acute coronary syndrome and 117 days of life expectancy obtained with TAVR versus standard therapy in patients with severe aortic stenosis deemed ineligible for surgery. Conclusions: Using outcome postponement as an additional measure of treatment effect is likely to be more easily understood than hazard ratio or RRR by both patients and physicians and could help when evaluating drugs. [ABSTRACT FROM AUTHOR]