Clinical Briefs
By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville
Dr. Kuritzky is a retained consultant for Boehringer Ingelheim, Daiichi Sankyo, Forest Pharmaceuticals, Janssen, Lilly, Novo Nordisk, Pfizer, and Sanofi.
Long-Term Risk-Reduction Benefits of Sigmoidoscopy and Colonoscopy
Source: Nishihara R, et al. Long-term colorectal-cancer incidence and mortality after lower endoscopy. N Engl J Med 2013;369:1095-1105.
Participants from two large observational studies provide an opportunity to evaluate the risk reduction accrued from either colonoscopy (COL) or sigmoidoscopy (SIG). The Nurses’ Health Study (n = 121,700 female nurses) and the Health Professionals Follow-up Study (n = 51,529 male health professionals) have more than 20 years’ prospective follow-up of their participants. During this interval, there were 1185 cases of colon cancer and 474 deaths from colon cancer.
Skeptics have long held fast to the tenet that SIG had an advantage over COL: proven risk reduction for colon cancer mortality for the former. Although the intuitive additional advantage of examining the entire colon with COL seemed a no-brainer, purists argued that whether COL was truly better than SIG was not yet proven, and that since COL was associated with greater risks (perforation, adverse effects from sedation, etc.), there was reasonable basis to continue with SIG as a preferred method. In accord with this philosophy, noting the many missed opportunities for colon cancer screening and prevention, advocacy groups rallied around the call-to-action, "The best colon cancer screening test is whichever one you can get done!"
These data may change that perspective, since the risk reduction for colon cancer death was almost twice as great for COL as SIG (hazard ratios, 0.59 vs 0.32). The "no-brainer" part of the equation was also resoundingly confirmed: COL reduced mortality from proximal colon cancer by more than half compared to no risk reduction through SIG.
Consequences of Non-Adherence in Treated Hypertensives
Source: Cummings DM, et al. Medication adherence and stroke/TIA risk in treated hypertensives: Results from the REGARDS study. J Am Soc Hypertens 2013;7:363-369.
The relationship between elevated blood pressure (BP) and stroke is linear and continuous. An abundance of clinical trial data indicate that treatment of hypertension (HTN) by means of numerous diverse classes of antihypertensives lowers stroke risk by ≥ 40%. Clinical trials, however, are not "real life." The Reasons for Geographic and Racial Disparities in Stroke (REGARDS) study is examining a large population (n = 30,239) of southeastern men and women with HTN. Their assessment of the relationship between self-reported degree of antihypertensive medication adherence and serious outcomes (stroke/TIA) from a subset population (n = 15,071) is quite sobering.
During a 5-year window of observation, study participants were grouped into four categories of adherence using the Morisky scale, which translates into general groupings of high, good, moderate, and low adherence. Perhaps not surprisingly, mean systolic BP in the high adherence group was substantially better than the low adherence group (131 mmHg vs 138 mmHg). Incidence of stroke or TIA was 8% higher in the lowest adherence group compared to the highest. Good BP control has meaningful payoff; every decrement of adherence less than that is costly.
Warfarin Outperforms Dabigatran in Patients with Mechanical Heart Valves
Source: Eikelboom JW, et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med 2013;369:1206-1214.
The atrial fibrillation (af) headlines have been filled with celebration over the efficacy of factor Xa inhibitors (e.g., rivaroxaban, apixaban) and direct thrombin inhibitors (e.g., dabigatran) for prevention of thrombotic events. Since warfarin — though highly effective, exhaustively studied, and time-tested — also has distinct clinical burdens (e.g., need for monitoring, food interactions, drug interactions), agents that were at least as efficacious for thrombotic risk reduction — with fewer of these same clinical burdens — were welcomed.
Success in AF, however, does not necessarily translate into other pathologies. Eikelboom et al studied patients with recent mitral or aortic mechanical valve replacement (n = 252). Subjects were randomized to dabigatran or warfarin. About one-fourth of these patients also had AF.
The trial had to be discontinued early because of untoward events in the dabigatran group: stroke occurred in 5% of the dabigatran group vs none in the warfarin group, and major bleeding was twice as common on dabigatran (4% vs 2%). Although earlier trials in animals were encouraging, these data indicate that warfarin is safer and better tolerated in patients with recent surgery for prosthetic mechanical heart valves.
