New onset diabetes with statins, caused by the drug or cholesterol reduction?
In this meta-analysis of 8 large randomized controlled trials the percentage LDL-C reduction predicted the new onset of diabetes. Reductions of 30% - 40% and 40% - 50% of respectively 13% (OR = 1.13; 95% CI 1.01-1.26) and 29% (OR = 1.29; 95% CI 1.13-1.47). Overall patient using a statin had an increased risk of 11% (OR = 1.11; 95% CI 1.03-1.20). The group that used intensive LDL-C lowering statins had an 18% increase in the likelihood of developing diabetes (OR = 1.18; 95% CI, 1.10-1.28). The authors concluded that LDL-c reduction is the most appropriate parameter related to new onset of diabetes and that all patients with LDL-C reductions > 30% should be monitored on a regular basis
Wang S, Cai R, Yuan Y et al. Association between reductions in low-density lipoprotein cholesterol with statin therapy and the risk of new-onset diabetes: a meta-analysis. Scientific reports
2017; 7:39982. http://www.ncbi.nlm.nih.gov/pubmed/?term=28071756
Reduced platelet reactivity and vitamin D increase after switch to a high intensity statins dosage
Exploring the pleiotropic effects of statins was the aim of this cross sectional observational study. In total 246 Italian CHD patients were analyzed 30 - 90 days after PCI and/or ACS event. There were 142 patients discharged on a new statin or switched to a high intensity statin dosage (Atorvastatin ≥ 20 mg; Rosuvastatin ≥10 mg or Simvastatin ≥40 mg) ; 104 patients remained on the high intensity statin they were using. Vitamin D plasma concentration increased and platelet agreeability decreased only in patients that were up titrated. Plasma calcium concentrations increased and LDL-cholesterol decreased. There was a linear relationship between the Vitamin D increase and LDL-C decrease. No difference in anti-platelet medication between the two groups and patients that increased the satins dosage were at higher risk (older, ↑diabetics, ↑hypertensives, ↑hypercholesterolemics, ↑ACS patients; less patients using anti-hypertensive medication and nitrates). Authors suggest that the pleiotropic benefits of statins could be (partely) related to the both increase of vitamin D lower platelet reactivity.
How your diabetic patients with CAD + leg amputation can get a 90% MACE reduction in 1 year!
Diabetic patients with CAD and PAD have a very high risk for recurrent events and death. In 2013, 179 diabetic patients with CAD and leg amputation were followed for 1 year. The intervention was a combination of Lifestyle advice (healthy diet, stop smoking and >30 min/day of physical activity) and the combination of statins, anti-hypertensives, anti-diabetic medication and dual anti platelets drugs. Of the 77 (44%) compliant patients (> 80% of prescribed pill count) 3 patients suffered an AMI vs 40 pts in the non-compliant group. Two patients died vs 26 deaths in the con-compliant group. The worse outcomes were observed in patients with extensive CAD, two- and three-vessel disease as compared to the ones with one-vessel disease or no obstructions. The one year MACE rate in these patients were: 95.24%, 70.5%, 17.2% and 8.6% respectively. Significant changes were already observed 10 days (!) post-surgery; deaths: 10(9.8%) vs 0 and AMI: 16 (15.6%) vs 3 (3.9%). Compliance to simple lifestyle and guideline dictated medication is pivotal when aiming to reduce events or death in very high risk patients.
Shalaeva EV, Saner H, Janabaev BB, Shalaeva AV. Tenfold risk increase of major cardiovascular events after high limb amputation with non-compliance for secondary prevention measures. Eur J Prev Cardiol
Using internet postings as a pharmacovigilance tool for statins side effects
Using an internet site dedicated to share experiences with drugs, investigators examined the robustness of the published data for pharmacovigilance. This retrospective cross-sectional study collected public available date on a single day in 2012. They scored 96 narratives on adverse drug reactions (ADR’s) for statins on 16 key criteria. The 72 patients (40 women, 32 men mean age 59 years) reported 176 ADR’s. Most frequent reports reflected on musculoskeletal problems (42.6%) and nervous system disorders (15.3%). Only 2 patients (3%) reported ADR’s that could be considered serious: hospitalization and visit to emergency room. Changing or stopping their lipid lowering medication was reported by 24 patients (33%). On average 6/16, key elements were available per narrative, most frequently lacking were medical history (87%) and concomitant medication (86%). The authors conclude that Internet posts are an important and valuable source for surveying patient reported ADR’s, however the information should be interpreted cautiously and further assessed for relevance by using a post-marketing surveillance approach.
Should you prescribe statins to patients with renal disease?
Patients with early stages of chronic kidney disease (CKD) showed better outcomes when using statins but in advanced disease (eGFR <30ml/min/1.73 m2) this was not the case. This Korean retrospective analysis (2003 – 2013) using data from a single hospital, analyzed 14 497 CKD patients; 1 955 patients (13.5%) used statins; 858 statin users, were paired with non-users after which a propensity score matching was implemented. Overall only the patients with eGFR>30/min/1.73 m2 showed superior outcomes. A delay of serum Creatinine doubling (HR, 0.824; 95% CI, 0.722±0.939; P = 0.004) was observed in the unmatched cohort (independent of eGFR!) but not in the matched cohort. The Incidence of creatinine doubling was less both the unmatched (HR,0.744; 95% CI, 0.635±0.873; P < 0.001) and matched (HR, 0.767; 95% CI, 0.596±0.986; P = 0.039) cohorts. Risk of dying was reduced in both the unmatched (HR, 0.518; 95% CI, 0.365±0.734; P < 0.001 and matched (HR, 0.457; 95% CI, 0.214±0.979; P = 0.044) cohorts as well. In the patients with an eGFR <30 mL/min/1.73 m2. No mortality benefits due to statins could be determined. The authors concluded that initiation of statins in patients with early CKD may provide protection, however randomized controlled clinical trials are needed to furnish the final proof.
Predicting recurrent events in SPARCLE study using Oxidized-Phospholipids on apo-B
Improving CVD risk prediction by measuring OxPL –apoB showed promise. Patients in the randomized controlled clinical outcome trial SPARCLE, suffered from prior cerebrovascular events. The study showed that Atorvastatin 80 mg protects against stroke recurrence and coronary events. In this retrospective subgroup analysis, patients with elevated plasma levels of Ox-PL-apoB (highest quartile), were at much higher risk for recurrent stroke (HR: 4.3; p < 0.0001), first major coronary events (HR: 4.0; p < 0.0001), and any cardiovascular event (HR: 4.4; p < 0.0001). At baseline, there was no difference in OxPL concentrations between patients randomized to Atorvastatin or placebo. However, Patients experiencing a stroke recurrence had higher baseline levels. Median: 15.5 nmol/l (interquartile range [IQR]: 11.0 to 21.3 nmol/l) versus 11.6 nmol/l (IQR: 6.3 to 18.2 nmol/l), p < 0.0001. Baseline levels in patients with diabetes were elevated as well compared to those without DM (mean 13.1 nmol/l [IQR: 7.3 to 19.0 nmol/l] vs. 12.0 nmol/l [IQR: 6.6 to 18.6 nmol/l]; p = 0.0389). Taking Atorvastatin did not influence the outcomes. Lp(a) is the particle associated with OxPL, they carry >85% of all lipoprotein associated OxPL. Statins are known to not only increase Lp(a) (±10%) but OxPL-apoB (±24%) as well. Although in SPARCL OxPL-Apob declined in both treatment arms, this could reflect the acute phase response after the stroke that tapered off after 6-8 months. Unfortunately, Lp(a) was not measured in SPARCL and OxPL-apoB was only measured at baseline and at study completion. The Authors concluded that OxPL-apoB levels are an independent and clinically informative biomarker in predicting cerebrovascular events in post stroke patients and further research could reveal potentially novel biological pathways and disover new modalities to target OxPL directly to reduce risk.