Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

What is the evidence for physical therapy poststroke? A systematic review and meta-analysis

BACKGROUND: Physical therapy (PT) is one of the key disciplines in interdisciplinary stroke rehabilitation. The aim of this systematic review was to provide an update of the evidence for stroke rehabilitation interventions in the domain of PT. METHODS AND FINDINGS: Randomized controlled trials (RCTs) regarding PT in stroke rehabilitation were retrieved through a systematic search. Outcomes were classified according to the ICF. RCTs with a low risk of bias were quantitatively analyzed. Differences between phases poststroke were explored in subgroup analyses. A best evidence synthesis was performed for neurological treatment approaches. The search yielded 467 RCTs (N = 25373; median PEDro score 6 [IQR 5-7]), identifying 53 interventions. No adverse events were reported. Strong evidence was found for significant positive effects of 13 interventions related to gait, 11 interventions related to arm-hand activities, 1 intervention for ADL, and 3 interventions for physical fitness. Summary Effect Sizes (SESs) ranged from 0.17 (95%CI 0.03-0.70; I(2) = 0%) for therapeutic positioning of the paretic arm to 2.47 (95%CI 0.84-4.11; I(2) = 77%) for training of sitting balance. There is strong evidence that a higher dose of practice is better, with SESs ranging from 0.21 (95%CI 0.02-0.39; I(2) = 6%) for motor function of the paretic arm to 0.61 (95%CI 0.41-0.82; I(2) = 41%) for muscle strength of the paretic leg. Subgroup analyses yielded significant differences with respect to timing poststroke for 10 interventions. Neurological treatment approaches to training of body functions and activities showed equal or unfavorable effects when compared to other training interventions. Main limitations of the present review are not using individual patient data for meta-analyses and absence of correction for multiple testing. CONCLUSIONS: There is strong evidence for PT interventions favoring intensive high repetitive task-oriented and task-specific training in all phases poststroke. Effects are mostly restricted to the actually trained functions and activities. Suggestions for prioritizing PT stroke research are given