ESC 2015 provides important updates on hypertension, CVD, diabetes with implications on primary clinical practice
Editors: Dr. Reuben C. Ricallo . Dr. Ereka C. Ricafranca
JOHN MANDROLA, MD provided some highlights of selected studies presented at the recently concluded European Society of Cardiology 2015 meeting in London, U.K. that can be informative and useful primary care practice. These highlights was published in Medscape Internal Medicine.
Twists and turns in hypertension
Several studies were presented on the management of patients with hypertension—both nonpharmacologic and drug therapies. These are some key messages:
1. Spironolactone in resistant hypertension. In the general hypertensive population the average physician sees in the clinic, around 10 percent or one in 10 has drug-resistant hypertension. The prospective, randomized Optimal Treatment of Drug-Resistant Hypertension— PATHWAY2 trial showed that the addition of spironolactone in patients treated with renin-angiotensin- aldosterone system blockers, calcium-channel blockers, and a thiazide- like diuretic resulted in a significant reduction in systolic blood pressure (BP).
Systolic BP decreased by 12.8 mm Hg on average during the 12 weeks of treatment. If one looks at the in-clinic reduction observed, which was approximately 20-mm Hg reduction from baseline, the benefit in terms of BP control is even more significant. To reiterate, this is additional BP control in a difficult-to-treat patient population.
2. Amiloride-HCTZ combination. An amiloride-hydrocholorothiazide (HCTZ) combination was shown in a separate trial—Comparison of Single and Combination Diuretics in Low-Renin Hypertension (PATHWAY3)—to offer an additional BP reduction in patients with uncontrolled hypertension (systolic BP > 140 mm Hg) who had at least one additional component of the metabolic syndrome.
In the trial, patients were randomly assigned to receive amiloride 10-20 mg, HCTZ 25-50 mg, or amiloride 5-10 mg plus HCTZ 12.5-25 mg. The two full-dose agents both decreased systolic BP approximately 14 mm Hg, but there was an additional reduction of 3.4 mm Hg in patients treated with the amiloride/HCTZ combination. The trialists reported that the combination was safe, with a neutral effect on both potassium levels and two-hour glucose levels.
3. Prescribe a nap. Another prospective, observational study of patients with well-controlled hypertension, which classified subjects as midday “nappers” or “nonnappers” on the basis of questionnaire responses, showed that those who slept for 60 minutes, typically after a midday meal, had a 5 percent lower average 24-hour ambulatory systolic BP than the nonnappers, even after adjusting for age, gender, body mass index, smoking status, salt intake, alcohol intake, exercise, and coffee consumption. Another favorable finding also was that nappers tended to use fewer medications than nonnappers. So, a short midday nap may be prescribed as part of lifestyle intervention.
4. Depression factor. Hypertension and depression make bad company to each other. A study involving over 35,000 primary care patients with heart disease, diabetes, or stroke showed an 83 percent higher relative risk for CV events in those with both depression and high systolic BP vs. those without both conditions. Conversely, those with depression and very low systolic BP had a 36 percent higher relative risk for CV events. No association was found between CV event risk and diastolic BP plus depression. So physicians must always screen for signs and symptoms of depression and try to keep the BP within optimal levels.
CVD and diabetes
Other papers presented in the ESC congress also offered clinically important findings.
1. Ezetimibe in ACS. A prespecified analysis in the IMPROVE-IT trial, a study examining the effects of the nonstatin, cholesterol-lowering drug ezetimibe, found that the 4,933 patients (27 percent) with diabetes and acute coronary syndrome benefited from the drug compared to nondiabetics. Based on the results, the benefit in patients with diabetes included a 24 percent reduction in myocardial infarction (MI) and a 39 percent reduction in ischemic stroke compared with patients who took ezetimibe but did not have diabetes. There were no safety signals noted.
However, this benefit to diabetics is to be interpreted with caution because the number needed to treat to prevent a single coronary event was quite high (NNT=200); and there was no mortality benefit. The cost implications are large, which may not make it that cost-effective. It was also noted that in the original trial, add-on ezetimibe was barely positive against simvastatin 40 mg daily, which is considered a weak comparator.
2. Sitagliptin safety. A question that begs an answer is if this dipeptidyl peptidase 4 (DPP-4) inhibitor is associated with a lower rate of heart failure (HF) since another DPP4-inhibitor (saxagliptin) showed some (HF) safety concerns in another trial (SAVOR-TIMI). A prespecified secondary analysis of data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), which enrolled more than 2,600 patients with prior heart failure found no difference in total heart failure events (first and recurrent events) or mortality among patients with at least one hospitalization for heart failure in the sitagliptin-treated patients. TECOS was designed as a safety study, and the trial found no significant difference between sitagliptin and placebo in terms of a composite endpoint of CV death, nonfatal MI, nonfatal stroke, or hospitalization for unstable angina.
This TECOS secondary analysis gives an assurance that the HF “red flag” noted with saxagliptin is not a class finding true for all DPP4 inhibitors.
3. NSAIDs and CV safety. This has been a decade-long issue; and the results of the Standard care versus Celecoxib Outcome Trial (SCOT) provide reassurance that celecoxib, a selective cyclooxygenase 2 (COX-2) inhibitor associated with concerns about elevated risk for MI in patients with CV disease (CVD), is as safe for chronic therapy as non–COX-selective (ns) NSAIDs. The SCOT trialists also allayed concerns that even the older, mainstay ns-NSAIDs like diclofenac and ibuprofen in their trial, pose an untoward CV risk.
Patients enrolled in the trial had no established CVD, but many had CV risk factors. The authors reported that serious adverse events were essentially equal, at 31.7 percent for the celecoxib group and 32.4 percent for the ns-NSAID group, but the absolute rate of cardiac events was low in both groups—approximately 1 percent. The trial was randomized but was not double-blind.
In a study involving a nationwide propensity-matched cohort of Danish patients with heart failure and atrial fibrillation, the use of digoxin was associated with slightly improved survival. This benefit was greater in patients with more severe heart failure. However, the rate of hospital readmission was not statistically different in the digoxin-treated patients vs the control patients.
The authors however clarified that the patients treated with digoxin were younger than control patients (mean age, 74 vs. 76 years; P < 0.001). CV risk factors including hypertension, CVD, chronic renal failure, and diabetes tended to be less also in the digitalis group. They were also less likely to receive concomitant angiotensin- converting enzyme inhibitors or angiotensin-receptor blockers, beta-blockers, spironolactone, or statins, but they were more likely to be receiving loop diuretics.
To date, there are no randomized controlled trial which has proven that digoxin reduces mortality in patients with heart failure. Observational trials have shown mixed results. In this trial, the relatively favorable results could be explained by the fact that digoxin seems most useful when used in patients with both atrial fibrillation and heart failure.
Vital Signs Issue 80 Vol. 4, October 1-31 2015