Applying trial evidence back to the patient in the clinical setting is often the most difficult and neglected step in the practice of evidence-based medicine.
|Antiplatelets in Ischaemic Stroke and TIA||Authors||Outcome|
|The European Stroke Prevention Study (ESPS).Lancet. 1987;2(8572):1351. || The ESPS Group.||In a multicentre double-blind trial, 2500 patients with a clinical diagnosis of a recent cerebrovascular event of atherothrombotic origin (TIA, RIND or stroke) were randomised to receive either dipyridamole 75 mg plus acetylsalicylic acid 325 mg (DP-ASA, 1250 patients) or placebo (1250 patients) thrice daily. Follow-up was 24 months. On intention-to-treat analysis, 473 patients reached an end-point (stroke or death from any cause), 190 on DP-ASA and 283 on placebo. Survival curves for end-points showed 33% benefit in favour of the DP-ASA group (p less than 0.001). 108 patients died in the DP-ASA group and 156 in the placebo group (p less than 0.01). |
|CAST 1997 |
CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with AIS.
|CAST (Chinese Acute Stroke Trial) Collaborative Group.||The Aspirin treatment (160 mg/day) started within 48 h of the onset of suspected AIS and continued in hospital for up to 4 weeks. Significant 14% (SD 7) proportional reduction in mortality during the scheduled treatment period (343 [3.3%] deaths among aspirin-allocated patients vs 398 [3.9%] deaths among placebo-allocated patients; 2p = 0.04). Significantly fewer recurrent AIS in the aspirin-allocated than in the placebo-allocated group (167 [1.6%] vs 215 [2.1%]; 2p = 0.01) but slightly more haemorrhagic strokes (115 [1.1%] vs 93 [0.9%]; 2p > 0.1). For the combined in-hospital endpoint of death or non-fatal stroke at 4 weeks, there was a 12% (6) proportional risk reduction with aspirin (545 [5.3%] vs 614 [5.9%]; 2p = 0.03), an absolute difference of 6.8 (3.2) fewer cases per 1000. At discharge, 3153 (30.5%) aspirin-allocated patients and 3266 (31.6%) placebo-allocated patients were dead or dependent, corresponding to 11.4 (6.4) fewer per 1000 in favour of aspirin (2p = 0.08).|
IST 1997The International Stroke Trial (IST): a randomised trial of aspirin, S/C UFH, both, or neither in AIS. ||International Stroke Trial Collaborative Group||19435 patients with AIS. Heparin (UFH 5000 or 12,500 IU BD) did not offer any clinical advantage at 6 months. If used the dose should not exceed 5000 IU SC BD. Aspirin has a small but worthwhile improvement at 6 months. Taking the IST together with the comparably large Chinese Acute Stroke Trial, aspirin produces a small but real reduction of about 10 deaths or recurrent strokes per 1000 during the first few weeks. Both trials suggest that aspirin should be started as soon as possible after the onset of ischaemic stroke.|
|CHANCE trial 2013|
Clopidogrel with aspirin in acute minor stroke or TIA .N Engl J Med. 2013;369:11-19
|CHANCE Investigators*|| DAPT to prevent secondary stroke within the first 90 days following a qualifying TIA or minor stroke in 5170 Chinese patients. Stroke occurred in 8.2% of patients in the clopidogrel-aspirin group, as compared with 11.7% of those in the aspirin group (hazard ratio, 0.68; 95% confidence interval, 0.57 to 0.81; P<0.001). Moderate or severe haemorrhage occurred in seven patients (0.3%) in the clopidogrel-aspirin group and in eight (0.3%) in the aspirin group (P=0.73); the rate of haemorrhagic stroke was 0.3% in each group. CONCLUSIONS: Among patients with TIA or minor stroke who can be treated within 24 hours after the onset of symptoms, the combination of clopidogrel and aspirin is superior to aspirin alone for reducing the risk of stroke in the first 90 days and does not increase the risk of haemorrhage.|
|SOCRATES trial 2016|
Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack
|S. Claiborne Johnston, M.D., Ph.D., Pierre Amarenco, M.D., Gregory W. Albers, M.D., Hans Denison, M.D., Ph.D., J. Donald Easton, M.D., Scott R. Evans, Ph.D., Peter Held, M.D., Ph.D., Jenny Jonasson, Ph.D., Kazuo Minematsu, M.D., Ph.D., Carlos A. Molina, M.D., Yongjun Wang, M.D., and K.S. Lawrence Wong, M.D. for the SOCRATES Steering Committee and Investigators*||Patients with non-severe ischaemic stroke or high-risk transient ischemic attack who had not received intravenous or intraarterial thrombolysis and were not considered to have had a cardioembolic stroke were randomly assigned within 24 hours after symptom onset. During the 90 days of treatment, primary end-point event in 442 of the 6589 patients (6.7%) treated with ticagrelor, versus 497 of the 6610 patients (7.5%) treated with aspirin (hazard ratio, 0.89; 95% confidence interval [CI], 0.78 to 1.01; P=0.07). Ischaemic stroke occurred in 385 patients (5.8%) treated with ticagrelor and in 441 patients (6.7%) treated with aspirin (hazard ratio, 0.87; 95% CI, 0.76 to 1.00). Major bleeding occurred in 0.5% of patients treated with ticagrelor and in 0.6% of patients treated with aspirin, intracranial haemorrhage in 0.2% and 0.3%, respectively, and fatal bleeding in 0.1% and 0.1%. Conclusions: Ticagrelor was not found to be superior to aspirin in reducing the rate of stroke, myocardial infarction, or death at 90 days. |
|POINT trial 2018|
Clopidogrel and Aspirin in AIS and High-Risk TIA
| S. Claiborne Johnston, M.D., Ph.D., J. Donald Easton, M.D., Mary Farrant, M.B.A., William Barsan, M.D., Robin A. Conwit, M.D., Jordan J. Elm, Ph.D., Anthony S. Kim, M.D., Anne S. Lindblad, Ph.D., and Yuko Y. Palesch, Ph.D. for the Clinical Research Collaboration, Neurological Emergencies Treatment Trials Network, and the POINT Investigators||4881 Chinese patients with minor AIS or high-risk TIA Given clopidogrel at a loading dose of 600 mg on day 1, followed by 75 mg per day, plus aspirin (at a dose of 50 to 325 mg per day) or the same range of doses of aspirin alone. 4881 patients. Trial halted as determined that the combination of clopidogrel and aspirin was associated with both a lower risk of major ischaemic events and a higher risk of major haemorrhage than aspirin alone at 90 days. Major ischemic events occurred in 121 of 2432 patients (5.0%) receiving clopidogrel plus aspirin and in 160 of 2449 patients (6.5%) receiving aspirin plus placebo (hazard ratio, 0.75; 95% confidence interval [CI], 0.59 to 0.95; P=0.02), with most events occurring during the first week after the initial event. Major haemorrhage occurred in 23 patients (0.9%) receiving clopidogrel plus aspirin and in 10 patients (0.4%) receiving aspirin plus placebo (hazard ratio, 2.32; 95% CI, 1.10 to 4.87; P=0.02). Conclusions: In patients with minor ischemic stroke or high-risk TIA, those who received a combination of clopidogrel and aspirin had a lower risk of major ischemic events but a higher risk of major haemorrhage at 90 days than those who received aspirin alone.|
Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial. Lancet 2018; 391: 850-59
|Prof Philip M Bath, Lisa J Woodhouse, MSc, Jason P Appleton, MRCP[UK], Maia Beridze, MD, Prof Hanne Christensen, DMSci, Robert A Dineen, FRCR et al. || Patients with AIS or TIA within 48 h of onset. Assigned in a 1:1 ratio to loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg BD) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67-1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05-3·16, p<0·0001).|
|BP Lowering in Acute Haemorrhagic Stroke||Authors||Outcome|
|Rapid BP lowering in patients with acute intracerebral haemorrhage.(INTERACT2) N Engl J Med. 2013 Jun 20;368(25):2355-65||Anderson CS, Heeley E, Huang Y, Wang J, Stapf C, Delcourt C, Lindley R, Robinson T, Lavados P, Neal B, Hata J, Arima H, Parsons M, Li Y, Wang J, Heritier S, Li Q, Woodward M, Simes RJ, Davis SM, Chalmers J; INTERACT2 Investigators. ||Randomized 2839 patients within 6 hours of having cerebral bleeding. Half of the patients achieved SBP < 140 mm Hg, with IV treatment with antihypertensive drugs. The control group received standard care. The endpoint was death or major disability. There was an odds ratio of 0.87 in favor of a more aggressive immediate lowering of blood pressure in patients with cerebral bleeds, which just failed significance. |
|Intensive BP reduction in acute intracerebral haemorrhage: a meta-analysis. Neurology. 2014 Oct 21;83(17):1523-9||Tsivgoulis G1, Katsanos AH2, Butcher KS2, Boviatsis E2, Triantafyllou N2, Rizos I2, Alexandrov AV2. ||Our findings indicate that intensive BP management in patients with acute ICH is safe. Fewer intensively treated patients had unfavorable 3-month functional outcome although this finding did not reach significance. Moreover, intensive BP reduction appears to be associated with a greater attenuation of absolute hematoma growth at 24 hours. |
|Intensive BP reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial. Lancet Neurol. 2008 May;7(5):391-9|| Anderson CS1, Huang Y, Wang JG, Arima H, Neal B, Peng B, Heeley E, Skulina C, Parsons MW, Kim JS, Tao QL, Li YC, Jiang JD, Tai LW, Zhang JL, Xu E, Cheng Y, Heritier S, Morgenstern LB, Chalmers J; INTERACT Investigators.|| Early intensive BP-lowering treatment is clinically feasible, well tolerated, and seems to reduce haematoma growth in ICH. A large randomised trial is needed to define the effects on clinical outcomes across a broad range of patients with ICH.|
|Effect of Routine Low-Dose Oxygen Supplementation on Death and Disability in Adults With Acute Stroke
The Stroke Oxygen Study Randomized Clinical Trial. JAMA. 2017;318(12):1125-1135||8003 patients with acute stroke were randomized within 24 hours of admission to 3 days of continuous oxygen, nocturnal oxygen, or control. ||After 3 months, there was no significant difference in death and disability for the combined oxygen groups compared with control (odds ratio, 0.97) or for the continuous oxygen group compared with the nocturnal oxygen group (odds ratio, 1.03). Meaning Routine low-dose oxygen did not improve outcomes in non hypoxic patients after acute stroke. |
|Efficacy of Nitric oxide (GTN), with or without continuing antihypertensive treatment, for management of high BP in acute stroke (ENOS): Lancet 2015; 385: 617-28 ||4011 patients enrolled with AIS or AHS and raised SBP.|| Mean BP was 167 (SD 19) mm Hg/90 (13) mm Hg at baseline (median 26 h [16-37] after stroke onset), and was significantly reduced on day 1 in 2000 patients allocated to GTN compared with 2011 controls (difference -7·0 [95% CI -8·5 to -5·6] mm Hg/-3·5 [-4·4 to -2·6] mm Hg; both p<0·0001), and on day 7 in 1053 patients allocated to continue antihypertensive drugs compared with 1044 patients randomised to stop them (difference -9·5 [95% CI -11·8 to -7·2] mm Hg/-5·0 [-6·4 to -3·7] mm Hg; both p<0·0001). Functional outcome at day 90 did not differ in either treatment comparison-the adjusted common odds ratio (OR) for worse outcome with GTN versus no GTN was 1·01 (95% CI 0·91-1·13; p=0·83), and with continue versus stop antihypertensive drugs OR was 1·05 (0·90-1·22; p=0·55).n patients with acute stroke and high blood pressure, transdermal GTN lowered blood pressure and had acceptable safety but did not improve functional outcome. We show no evidence to support continuing prestroke antihypertensive drugs in patients in the first few days after acute stroke. |
|Prehospital use of Magnesium sulfate as neuroprotection in acute stroke.FAST-MAG N Engl J Med. 2015 Feb 5;372(6):528-36||
Patients with suspected stroke given either IV magnesium sulfate or placebo, within 2 hours after symptom onset. Loading dose by paramedics prehospital. 24-hour maintenance infusion was started on the patient's arrival at the hospital. 1700 enrolled patients (857 in the Mg group and 843 placebo). The final diagnosis cerebral ischaemia in 73.3% of patients, ICH in 22.8%, and a mimicking condition in 3.9%. ||There was no significant shift in the distribution of 90-day disability outcomes on the global modified Rankin scale between patients in the magnesium group and those in the placebo group Prehospital initiation of magnesium sulfate therapy was safe and allowed the start of therapy within 2 hours after the onset of stroke symptoms, but it did not improve disability outcomes at 90 days.
| A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med. 2013;368:914-23. ||MR RESCUE Investigators. Kidwell CS, Jahan R, Gornbein J, et al||A favourable penumbral pattern on neuroimaging did not identify patients who would differentially benefit from endovascular therapy for acute ischemic stroke, nor was embolectomy shown to be superior to standard care.|
| Endovascular therapy for ischemic stroke with perfusion-imaging selection (EXTEND-IA). NEJM. 2015;372:1009-18. ||Campbell B, Mitchell P, Kleinig T, et al.||In patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging, early thrombectomy with the Solitaire FR stent retriever, as compared with alteplase alone, improved reperfusion, early neurologic recovery, and functional outcome|
|Stent-Retriever Thrombectomy after Intravenous t-PA vs. t-PA Alone N Engl J Med 2015; 372:2285-2295 DOI: 10.1056/NEJMoa1415061||SWIFT PRIME Investigators* || In patients receiving intravenous t-PA for acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, thrombectomy with a stent retriever within 6 hours after onset improved functional outcomes at 90 days. (Funded by Covidien; SWIFT PRIME ClinicalTrials.gov number
| Endovascular therapy for acute ischaemic stroke: the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) randomised, controlled trial. J Neurol Neurosurg Psychiatry 2017;88:38-44.|| Muir KW, Ford GA, Messow C on behalf of the PISTE Investigators, et al||The trial did not find a significant difference between treatment groups for the primary end point. However, the effect size was consistent with published data and across primary and secondary end points. Proceeding as fast as possible to MT after CTA confirmation of large artery occlusion on a background of intravenous alteplase is safe, improves excellent clinical outcomes and, in the per-protocol population, improves disability-free survival.|
|Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging February 22, 2018 N Engl J Med 2018; 378:708-718 DOI: 10.1056/NEJMoa1713973
||Gregory W. Albers, M.D.et al. for the DEFUSE 3 Investigators* ||Endovascular thrombectomy for ischemic stroke 6 to 16 hours after a patient was last known to be well plus standard medical therapy resulted in better functional outcomes than standard medical therapy alone among patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion and a region of tissue that was ischemic but not yet infarcted
|Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. January 4, 2018 N Engl J Med 2018; 378:11-21
||Raul G. Nogueira, M.D. et al. for the DAWN Trial Investigators||Among patients with acute stroke who had last been known to be well 6 to 24 hours earlier and who had a mismatch between clinical deficit and infarct, outcomes for disability at 90 days were better with thrombectomy plus standard care than with standard care alone. |
|Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333:1581-7. 2.
||The National Institute of Neurological Disorders and Stroke rt-PA Study Group.||Despite an increased incidence of symptomatic intracerebral haemorrhage, treatment with intravenous t-PA within three hours of the onset of ischaemic stroke improved clinical outcome at three months.|
|Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke: the European Cooperative Acute Stroke Study (ECASS). JAMA 1995;274:1017-1025||Hacke W, Kaste M, Fieschi C, et al. || Intravenous thrombolysis in acute ischemic stroke is effective in improving some functional measures and neurologic outcome in a defined subgroup of stroke patients with moderate to severe neurologic deficit and without extended infarct signs on the initial CT scan. However, the identification of this subgroup is difficult and depends on recognition of early major CT signs of early infarction. Therefore, since treating ineligible patients is associated with an unacceptable increase of haemorrhagic complications and death, intravenous thrombolysis cannot currently be recommended for use in an unselected population of acute ischemic stroke patients.|
|Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. NEJM. 2008;359:1317-29.ECASS 3
||Hacke W, Kaste M, Bluhmki E, et al.|| As compared with placebo, intravenous alteplase administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke; alteplase was more frequently associated with symptomatic intracranial haemorrhage.|
|The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial The Lancet , Volume 379 , Issue 9834 , 2352 - 2363 || The IST-3 collaborative group || For the types of patient recruited in IST-3, despite the early hazards, thrombolysis within 6 h improved functional outcome. Benefit did not seem to be diminished in elderly patients.|
|Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in AIS (ECASS II). Lancet. 1998; 352: 1245-1251 ||Hacke, W, Kaste, M, Fieschi, C et al. || The results do not confirm a statistical benefit for alteplase. However, we believe the trend towards efficacy should be interpreted in the light of evidence from previous trials. Despite the increased risk of intracranial haemorrhage, thrombolysis with alteplase at a dose of 0·9 mg/kg in selected patients may lead to a clinically relevant improvement in outcome.
Medical management with or without interventional therapy for unruptured brain arteriovenous malformations
(ARUBA): a multicentre, non-blinded, randomised trial. Lancet 383:614-621, 2014
||ARUBA trial Investigators.
||Randomisation started 2007, and stopped 2013, when a data and safety monitoring board recommended halting randomisation because of superiority of the medical management group (log-rank Z statistic of 4·10, exceeding the prespecified stopping boundary value of 2·87). At this point, outcome data were available for 223 patients (mean follow-up 33·3 months [SD 19·7]), 114 assigned to interventional therapy and 109 to medical management. The primary endpoint had been reached by 11 (10·1%) patients in the medical management group compared with 35 (30·7%) in the interventional therapy group. The risk of death or stroke was significantly lower in the medical management group than in the interventional therapy group (hazard ratio 0·27, 95% CI 0·14-0·54). No harms were identified, other than a higher number of strokes (45 vs 12, p<0·0001) and neurological deficits unrelated to stroke (14 vs 1, p=0·0008) in patients allocated to interventional therapy compared with medical management. The ARUBA trial showed that medical management alone is superior to medical management with interventional therapy for the prevention of death or stroke in patients with unruptured brain arteriovenous malformations followed up for 33 months. The trial is continuing its observational phase to establish whether the disparities will persist over an additional 5 years of follow-up.
|Stenting for Intracranial stenosis||Authors||Outcome|
Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis (SAMMPRIS)
||SAMMPRIS Trial Investigators*
Enrolment stopped after 451 patients as 30-day rate of stroke or death was 14.7% in the PTAS group (nonfatal stroke, 12.5%; fatal stroke, 2.2%) and 5.8% in the medical-management group (nonfatal stroke, 5.3%; non-stroke-related death, 0.4%) (P=0.002). Beyond 30 days, stroke in the same territory occurred in 13 patients in each group. Currently, the mean duration of follow-up, which is ongoing, is 11.9 months. The probability of the occurrence of a primary end-point event over time differed significantly between the two treatment groups (P=0.009), with 1-year rates of the primary end point of 20.0% in the PTAS group and 12.2% in the medical-management group. In patients with intracranial arterial stenosis, aggressive medical management was superior to percutaneous transluminal angioplasty and stenting (PTAS) with the use of the Wingspan stent system, both because the risk of early stroke after PTAS was high and because the risk of stroke with aggressive medical therapy alone was lower than expected.
Anticoagulation for AF
|Anticoagulation for AF||Authors||Outcome|
Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation September 8, 2011 N Engl J Med 2011; 365:883-891
||The ROCKET AF Steering Committee et al. for the ROCKET AF Investigators*||
In patients with atrial fibrillation, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism. There was no significant between-group difference in the risk of major bleeding, although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group|
Dabigatran versus Warfarin in Patients with Atrial Fibrillation
N Engl J Med 2009; 361:1139-1151
||The RE-LY Steering Committee and Investigators
||In patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major haemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major haemorrhage.
Apixaban versus Warfarin in Patients with Atrial Fibrillation
N Engl J Med 2011; 365:981-992 ||ARISTOTLE Committees and Investigators*
||In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality
Edoxaban versus Warfarin in Patients with Atrial Fibrillation N Engl J Med 2013; 369:2093-2104
||ENGAGE AF-TIMI 48 Investigators*||
Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes.
Lipid Lowering in Stroke
High-Dose Atorvastatin after Stroke or TIA. Engl J Med 2006; 355:549-559.
||The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators
Methods: 4732 patients with previous stroke/TIA 1-6 months prior to study and LDL 2.6-4.9 mmol and no known history of CAD. Randomized to Atorvastatin 80 mg/day or placebo and mean follow-up = 4.9 years.
Results: There were fewer strokes occurred in treatment group vs. placebo (p=0.05). There was a significant reduction of risk of stroke and TIA (OR=0.77; p<0.001). There was a significant reduction in LDL cholesterol levels and a 16% reduction in risk for fatal or nonfatal stroke when compared to placebo
Reduction of stroke events with pravastatin: the Prospective Pravastatin Pooling (PPP) Project. Circulation. 2001 23;103(3):387-92.
||Byington RP, Davis BR, Plehn JF, White HD, Baker J, Cobbe SM, Shepherd J
Combined results of the CARE and LIPID trials of 13,173 patients Results: Pravastatin associated with reduction in total strokes by 22% (95% CI: 7% to 35%, p=0.01) and a 25% reduction in nonfatal stroke (95% CI: 10% to 38%). Authors estimated would need to treat 588 patients per year to prevent one stroke. Post-hoc analysis of LIPID trial showed treatment benefits may extend to individuals with low LDL and HDL.
|Trial and link||Authors||Outcome|
|Trial and link||Authors||Outcome|