Alternative strategies to achieve cardiovascular mortality goals in china and india

High blood pressure is a leading modifiable risk factor cardiovascular disease (CVD) mortality which is why controlling this has become such a big focus for so many healthcare providers. The US currently uses a treat-to-target strategy. Europe on the other hand uses a benefit-based, tailored treatment strategy in which therapy is initiated for patients with high estimated CVD risk. Both of these emphasize that the goal of controlling blood pressure is not to lower it but to avoid CVD events. The team in this study used models to simulate adults ages 30 to 70 in divers populations. The study had three groups, the US method, the European method, and a hybrid of the two.

It turns out that the study showed that the treat-to-target would be the best model to use in both China and India to allow for the most decrease in risk for CVD related events. Less people would be treated under the other system although treatment strategies would be similar.

 

Basu S, Yudkin JS, Sussman JB, Millett C, and Hayward RA. Alternative strategies to achieve cardiovascular mortality goals in china and india. Circulation. 2016;133:840-48.

Long-term outcome of patients with chronic thromboembolic pulmonary hypertension

A rare complication of acute pulmonary embolism is chronic thromboembolic pulmonary hypertension which is characterized by fibrothrombotic obstructions of large pulmonary arteries in conjunction with small-vessel arteriopathy. The usual treatment for this is a surgery, pulmonary endarterectomy, but in patients who cannot be operated on, they can be treated with medicine. This study compares the effects and outcomes between two groups, one including pateints who receive an operation for their chronic thromboembolic pulmonary hypertension while the other group was only treated medicinally. This is the first study to take a prospective, large-scale, international registry of newly diagnosed patients with CTEPH and include patients who are operated on and those who are not. The most significant thing about it is how that it was long-term.

It turned out that sixty percent of patients were operated on and forty percent were not operated on either by their own decision or for medical reasons. In total, 143 patients died, 51 of which were operated on and 92 that were not operated on. The significant find was the fact that patients that were operated on had a significantly better long-term survival than not-operated patients. Patients were eight years younger, had higher six minutes walking distance and higher cardiac index for those who were operated on. Survival for not-operated patients at 3 years was on seventy percent compared to eighty-nine percent for those who were operated on. One of the biggest determinants of survival was actually the presence of comorbidities such as cancer, coronary disease, left heart failure, and chronic obstructive pulmonary disease. It is important to note that medically treated patients were sicker than the other patients. Another significant note is that patients were treated off-label with endothelin receptor antagonist or phosphodiesterase-5 inhibitor. The long-term effects of the recently improved drug needs to be further evaluated to see if this could lead to more problems down the road.

While reading this it made me realize that it is very difficult to tell what a medication will do to people over a very long period of time, and it is hard to find this out before many people are already taking it. I wonder what other medications could potentially lead to major problems for patients down the road that we do not know about yet.

Delcroix M, Lang I, Pepke-Zaba J, et al. Long-term outcome of patients with chronic thromboembolic pulmonary hypertension. Circulation. 2016;133:859-71.

Selective COX-2 inhibitors significantly reduce the occurrence of heterotopic ossification after hip arthroscopic surgery

A well known complication after hip arthroscopic surgery is heterotopic ossification (HO), the presence of bone in soft tissue. This complication can be as prevalent as 44% of patients when no prophylactic intervention is given. Although it is not totally understood how HO occurs, it is known that mesenchymal cells provide the origin for this, and they are activated by inflammatory mediated response in injured tissues. Low-dose irradiation and nonsteroidal anti-inflammatory drugs are the two most commonly used interventions for this problem of reducing and preventing HO. This study hypothesized that postoperative HO prophylaxis using 600 mg of etodolac once daily for two weeks would significantly reduce risk of HO in patients after surgery in comparison with a groups of patients who were treated by the same surgeon who did not receive NSAID prophylaxis. Their ultimate goal of the study was to evaluate the effectiveness of short-term selective COX-2 inhibitors (specific NSAID) when they are being used prophylactically for HO.

In this retrospective analysis of data gathered from a cohort of patients who underwent surgery by the same surgeon for the same reason, femoroacetabular impingement.  Although the study started out with 263 patients patients, 163 were included in the final analysis because 100 of them had to be excluded for various reasons including lost to follow-up, previous hip surgery or HO, and not meeting inclusion criteria. 100 patients were assigned to the control group and 63 were included in the group that received COX-2 inhibitor prophylaxis. In the control group, 35 of 100 patients developed HO. The patients were tested for HO 2 weeks, 6 months, and 1 year after surgery. The data did exhibit a significant difference between the control and study groups, as there were no patients in the study group who developed HO. This is the first study to ever look at a dose this low, half of the maximum, in attempting to prevent HO with this specific medication. It is significant that this research is able to show a short-term, selective NSAID can be used to effectively prevent HO in this patient population because it gives the patients much less of a risk of developing the GI side effects that are so closely associated with traditional NSAIDs.

It is interesting how choosing between medications in the same class can often be very significant when treating a patient and trying to keep them as healthy and happy as possible. In what other classes of drugs can this be significant?
Rath E, Warschawski Y, Maman E, et al. Selective COX-2 inhibitors significantly reduce the occurrence of heterotopic ossification after hip arthroscopic surgery. Sports Med. 2016;44:677-81.

Effect of ranibizumab on the decision to drive and vision function relevant to driving in patients with diabetic macular edema

Diabetic macular edema (DME) is a condition that affects a person’s eyesight that can happen after a diabetic patient develops retinopathy. A major issue with this condition is that it often affects the patient’s ability to drive because of their loss of visual acuity (VA). One medication, ranibizumab, is said to significantly lower the risk for substantial visual acuity either by itself or in combination with laser treatment compared to observation alone or macular laser alone. This study was done to specifically analyze and evaluate the impact that ranibizumab can have on the ability of DME patients to drive. There were three different methods involved: RESTORE, RIDE, and RISE. In RESTORE, patients were deemed eligible for laser surgery and had a VA letter score between 78 and 39. They were then either given ranibizumab monotherapy, ranibizumab combination therapy (with laser therapy), or laser monotherapy. In RIDE and RISE, patients either got sham injection, 0.3 mg ranibizumab, or 0.5 mg ranibizumab. Macular laser could be used in any arm as long as the participant met the requirements. In all the trial types, each patient only had one eye treated with the experimental treatment while the other one was treated with the standard of care.

Compared with sham or macular laser therapy in all three of the methods, ranibizumab therapy allowed patients with visual impairment due to DME to report at a greater frequency that they were driving at 12 or 24 months if they were not driving at the onset of treatment. Those using ranibizumab treatment reported less difficulty with driving during the daytime in familiar places, driving at night, and driving in difficult conditions, such as bad weather, during rush hour, on the freeway, or in city traffic. This study ultimately shows that a patient treated for DME with ranibizumab is more likely to be driving 24 months after they start taking the medication. This article made me happy that medication is advancing to allow patients to better manage other disease that come along with diabetes. There are so many complications that occur with this one disease that it is nice to see more and more improvements with them. It is amazing that medication can bring a patient’s eyesight that was almost totally gone back to where they can see well enough to drive. This type of improvement must be amazing for the patient.

 

Bressler NM, Varma R, Mitchell P, et al. Effect of ranibizumab on the decision to drive and vision function relevant to driving in patients with diabetic macular edema. JAMA Opthalmol. 2016;134:160-66.

Risks and Benefits Associated with Prestroke Antiplatelet Therapy Among Patients with Acute Ischemic Stroke Treated with Intravenous Tissue Plasminogen Activator

Many patients who present at a hospital with a stroke are already on blood thinners for one reason or another. It is known that intravenous tissue plasminogen activator (tPA) improves the outcomes of ischemic strokes, but the issue is that it also carries the risk for symptomatic intracranial hemorrhage (sICH), which is actually the worst complications that could come from acute ischemic stroke. Another factor is that the blood thinners that these patients are often taking before they have a stroke, which could increase the chances of sICH when the patient is given tPA. The study done by Xian and colleagues aimed to determine if there was a significant increase risk for patients on antiplatelet therapy who received tPA, evaluated the safety of this in groups who would be clinically relevant and investigate the association that exists between being on antiplatelets prior to tPA administration with clinical outcomes in these cases.

This study included patients who had acute ischemic stroke, received intravenous tPA without combination with endovascular treatment, and had been on an anticoagulant regime before the ischemic stroke. The patients were then broken down into groups based on the types of anticoagulant regimes they had been receiving. The endpoints that the study focused on included sICH, in hospital mortality, discharge ambulatory status and the modified Rankin Scale score that ranges from 0 (no symptoms) to 6 (death). Secondary endpoints included were life-threatening or serious systemic hemorrhage within 36 hours, any tPA complication within 36 hours, and discharge destination (home, hospice, inpatient rehabilitation facility, or skilled nursing facility).

The results of this study were interesting because they determined that patients taking anticoagulant therapy did have a higher risk for sICH if they were on anticoagulants just prior to the stroke when given tPA at the hospital. Despite this finding, patients who received tPA did not have higher in-hospital mortality and had better functional outcomes in terms of ambulatory status and mRS scores. This leaves the real judgement up to the health care professionals involved in different individual cases.

It is interesting when a study seems to come up with results that could lead health care professionals in two different directions.What factors could go into making the decision to use tPA or not when a patient presents with an acute ischemic stroke?

Xian Y, Federspiel JJ, Grau-Sepulveda M, et al. Risks and benefits associated with prestroke antiplatelet therapy among patients with acute ischemic stroke treated with intravenous tissue plasminogen activator. JAMA Neurol. 2016;73:50-59)

Immunosuppressive Medications and Squamous Cell Skin Carcinoma

It has been noted in that past that people who take immunosuppressive medication have been much more likely to be diagnosed with squamous cell skin carcinoma (SCSC), a specific skin cancer that is especially prominent in this population. The authors of this paper wanted to explore the difference in patients who took cyclosporine and azathioprine, an immunosuppressant that is also a known to allow skin cells to rapidly divide after UV exposure, and those who took mycophenolic acid, a newer immunosuppressant, and tacrolimus. These two regimens represent an older and a newer regimen, respectively, for those who have an organ transplant. This research team’s goal was to find out if the newer medication regimen allowed for a lower risk of SCSC. The study ultimately included patients who had received certain organs during a specific time frame, and then each confirmed SCSC case was matched with two similar patient cases to be the controls  based on a list of criteria. After being selected and grouped based on a simple interview that was mailed out, the participants completed an in-person interview that focused on their demographics, social history, family history, and their use of immunosuppressive drugs.

The two main objectives of the study were to determine if the mycophenolate medications had the same risk to cause skin cancer as azathioprine and to determine if the choice of calcineurin inhibitor impacted the risk for SCSC which would be cyclosporine versus tacrolimus. The final conclusion was that azathioprine’s association with an increased risk of SCSC was confirmed, but a new finding was that including mycophenolate whether with or instead of azathioprine showed a lower risk of SCSC. It was also determined that there was no significant difference between the calcineurin inhibitors in terms of SCSC risk. More research will be needed to determine if mycophenolate is actually protective against SCSC or if it just allows for less risk of this because there were not many patients who were on both azathioprine and mycophenolate.

Coghill AE, Johnson LG, Berg D, et al. Immunosuppressive medications and squamous cell skin carcinoma: nested case-control study within the skin cancer after organ transplant (SCOT) cohort. Am J Transplant. 2016;16:565-73.

Cancer prevention is something that is very important to me. I think that it is wonderful that these researchers are taking steps to look into ways to keep transplant patients health after their transplants. Could these types of issues be solved with other immunosuppressive agents that are on the market today? Are there ways to at least minimize the problems that come along with these types of drugs?

Dose-Response Relationship of Selective Serotonin Reuptake Inhibitors in Major Depressive Disorder

Selective serotonin reuptake inhibitors are generally accepted as a class of drugs that should be prescribed to those with major depressive disorder, especially in the most severe cases. There is really not much debate about this fact, however, there is still question and uncertainty about how to dose these medications. The APA guidelines today call for optimizing the dose as long as the side effects can be tolerated because it has been shown that the there is a flat dose-response curve within the therapeutic range for antidepressant medications in major depressive disorder. The authors of this meta-analysis believe that this statement may be flawed for two reasons. One, the data that supports this statement includes all antidepressants not just SSRIs, and the researchers from the previous meta-analysis that produced this guideline looked at dose as a categorical outcome instead of continuous which could have reduced their power to determine what the dose-response relationship is really like. This meta-analysis set out to determine whether higher doses of SSRIs really improved outcomes or not.

The authors of this paper only included very specific studies to ensure that they came to the most accurate conclusion. The inclusion criteria were data for both SSRI and placebo treated patients and used standardized, validated outcome measurements for depression. The exclusion criteria included patients less than 19 or older than 60, use of a cross-over design, dual diagnoses, non-SSRIs, not randomized, not placebo-controlled, and psychotherapy was given to either the control or active group. In the end, the team of authors concluded that SSRIs show a significant increase in efficacy when higher doses were administered. The analysis also found that the higher doses are associated with reduced tolerability because more people dropped out of the trials due to side effects at high doses of SSRIs. These results differed from the previous meta-analysis, showing that the dose response curve did not level-off until the very end of the dosing range. This new finding could possibly affect how doctors prescribe SSRIs because there could be evidence to indicate prescribing higher doses than the minimum therapeutic range could be more effective for patients but also more harmful.

 

Jakubovski E, Varigonda AL, Freemantie N, et al. Systematic Review and Meta-Analysis: Dose-Response Relationship of Selective Serotonin Reuptake Inhibitors in Major Depressive Disorder. Am J Psychiatry. 2016; 173: 174-83.

 

After reading this article, it makes me wonder how physicians in charge of treating a patient’s major depressive disorder would react. Would more physicians start their patients off at a dose in the middle of the dose response curve, or would they start off higher? If they started in the middle and their patient did not see any improvement, would they feel more comfortable increasing the dose or would the potential side effects still keep them from doing this?