geoffrey modest medical blogs

This comment was  sent to me by Elizabeth Russo, who worked on a formal evaluation of Entresto (the name of the combo drug valsartan/sacubitril) for the non-profit ICER (Institute for Clinical and Economic Review, at  http://icer-review.org/  ): [for my blog, see:  http://gmodestmedblogs.blogspot.com/2016/05/heart-failure-guidelines-new-meds.html  ] Controversies and Uncertainties  Criticisms of Entresto center on the PARADIGM-HF trial having compared the combination neprilysin inhibitor and ARB valsartan to the ACE inhibitor enalapril rather than to valsartan alone. Another critique relates to the fact that the pivotal trial was conducted only among patients who tolerated a “run-in” phase of treatment with enalapril followed by treatment with Entresto. There is also concern that neprilysin inhibition itself can potentiate angioedema. In fact, more patients in the treatment arm developed angioedema than did in the enalapril arm of the PARADIGM-HF trial (0.5% versus 0.2%). Fu

The FDA came out with yet another warning about the SGLT-2 inhibitors (sodium glucose co-transporter-2 inhibitors) used for diabetes. this time it was about canagliflozin, used in the CANVAS study (CANagliflozin cardioVascular Assessment Study), an ongoing study, where the first results were recently presented at the European Assn for the Study of Diabetes (EASD) annual meeting (see  http://www.jnj.com/news/all/phase-3-canvas-trial-show-canagliflozin-as-add-on-therapy-to-insulin-lowered-blood-sugar-levels-in-patients-with-type-2-diabetes-at-an-elevated-risk-for-cardiovascular-disease  ). 1718 patients on insulin were put on canagliflozin 100mg or 300 mg, finding a 0.65 and 0.73 reduction in A1c respectively, and the previously known/expected increase in genital mycotic infections in men and women, increased urination, hypotension, and increased incidence of UTIs. But, now the FDA noted that the independent data monitoring committee for the study found an increased risk of leg and foot

a new analysis of several older studies looked at the association of sodium urinary excretion, a marker of sodium intake, finding a complex relationship between that and cardiovascular events in patients both with and without hypertension (see  htn sodium cv events lancet2016  in dropbox, or  doi.org/10.1016/S0140-6736(16)30467-6 ​). details: --133,118 individuals (63,559 with hypertension; 69,559 without) from 4 large prospective studies: PURE (prospective urban rural epidemiological study, 156424 people; EPIDREAM with 17453 people, ONTARGET with 25620 people, TRANSCEND with 5926 people) --median age 55 (58.6 in those with hypertension, 50.5 in those without), from 49 countries, mean sodium excretion 4850 mg/d, 50% women, 45% from Asia, 40% <high school education, BMI 26, 60% nonsmokers/20% current smokers (though less in hypertensives: 16%), 40% medium/40% high physical activity, 33% current drinkers/63% never, 14% diabetic (more in hypertensives), mean BP 148/76 in hyperte

The Am Heart Assn/Am College of Cardiol just published their updated 2016 guidelines on the pharmacological therapy of heart failure (HF), focusing on the newer therapies (see  chf aha guidelines2106 circ2016  in dropbox, or  doi:10.1161/CIR.0000000000000435/-/DC1  ) details: --meds for Stage C (symptomatic) HF with reduced ejection fraction (HFrEF). clinical strategy is to use one of these meds in combo with evidence-based  b -blocker and aldosterone antagonist in appropriate patients.     --ACE-I  ( Lev el A e vidence) : reduces morbidity and mortality in patients with any stage of symptomatic HF (also in asymptomatic, as an aside), with or without coronary artery disease (CAD). associated with hypotension; renal insufficiency; elevated K; angioedema in <1%, though higher in women and black patients.      --ARBs (Level A evidence): thought to help also with decreasing angiotensin II production (which continues despite ACE-I through alternative enzymatic pathways). ARBs re

A meta-analysis challenged the published statistic of the protective effect of aspirin after a TIA or ischemic stroke, showing that the effect of aspirin is much greater than believed, especially if given within days of the event (s ee  stroke TIA early ASA  rx  lancet2016  in  dropbox , or  doi.org/10.1016/S0140-6736(16)30468-8   ) . details: --background:     --risk of recurrent stroke is 10% in the week after a TIA or minor stroke     --but many patients delay seeking medical attention for days-to-weeks after these events     --in the UK, 1/2 of recurrent strokes happen prior to seeking medical attention     --pre-hospital use of self-administered aspirin is often discouraged for fear of exacerbating intracerebral bleed     --BUT, hemorrhage is a rare cause of TIAs and is in <5% of minor strokes     ​--there are minimal data from RCTs on the effect of aspirin after TIA or minor stroke, with only observational data on the effect of aspirin on early benefits after

A huge observational study was done in France looking at women on oral contraceptives (OCs), looking at the relative dose of the hormones and the risk of pulmonary embolism (PE), ischemic stroke and MI ( http://www.bmj.com/content/353/bmj.i2002  ). details: --4,945,088 women aged 15-49 with at least one reimbursement for OCs and no prior history of cancer, PE, ischemic stroke or MI, between 2010-2012 --mean age 28, 34% used oral contraceptive with  20  m g  estrogen , --risk factors used in models:  age, socioeconomic dat a (SES), hypertensio n, diabetes, and some indirect measures of smoking (eg, getting nicotine replacement therapy) though smoking was not directly assessed in the database. the incidence of hypertension, diabetes or being prescribed nicotine replacement therapy were each <2%. --results:     --5,443,916 women-years of OC use     ​--1800 PEs (33/100K women-years), 1046 ischemic strokes  (19/100K women-years) , 407 MIs  (7/100K women-years)     --wome

A subgroup analysis of the SPRINT trial found improved clinical outcomes in community-dwelling patients >= 75yo on intensive blood pressure control ( see htn SPRINT trial elderly jama2016  in dropbox, or  doi:10.1001/jama.2016.7050 ). for an overall review/critique of SPRINT, see  http://gmodestmedblogs.blogspot.com/2015/11/tighter-blood-pressure-control-sprint.html    .  details: --in brief, the SPRINT trial involved 9361 patients, mean age 68 (but they had a pre-designated subgroup >=75 yo), randomized to SBP goals of <120 vs <140 and achieving SBP of 121 vs 136, then finding a pretty dramatic clinical benefit in those with the more aggressive blood pressure goal. The researchers did not determine the antihypertensives used, but encouraged using those with known cardiovascular benefit (diuretics, calcium blockers, ACE/ARB) --the current study is of the 2636 people were over >=75 (mean age 79.9, 38% women, 75% white/17% black/7% Hispanic, baseline BP 142/71, 10%

I decided to resend an email from 11/12/14 on initial orthostatic hypotension, with a few additional comments, because i am finding this issue to be so common in my older patients. I am concerned that there is often a combination of pretty common age- and morbidity-related problems, often with some combination of medication adverse effects (some of the most egregious being a - or  b -blockers, diuretics, narcotics, vasodilators including calcium-channel blockers or hydralazine), alcohol, morphine, dehydration (esp in the hotter times of the year), autonomic neuropathy (esp from diabetes), and just the plain old decrease in baroreceptor response with aging. And, I am a little concerned about being overaggressive with application of the SPRINT trial results to the elderly (which, of note, excluded diabetics), suggesting benefit for more aggressive BP management in older patients. (see  http://gmodestmedblogs.blogspot.com/2015/11/tighter-blood-pressure-control-sprint.html    . For a hist