Internal organ involvement reduces the life expectancy of SSc patients. Cardiopulmonary manifestations are currently the primary cause of death. We aimed to perform a systematic review and meta-analysis to define more precise effect estimates of different cardiopulmonary manifestations and to verify trends in the mortality of SSc. A systematic literature search was performed to identify relevant cohort studies. Reports analyzing the role of the organ manifestations in mortality or analysing survival compared with the control population were included. The outcome parameters were pooled with the random-effect model via generic inverse-variance weighting in conventional and cumulative meta-analysis. Eighteen studies comprising a total of 12, 829 patients qualified. The reported causes of death were as follows: 19.7% cardiac, 16.8% interstitial pulmonary disease, 13.1% pulmonary hypertension and 13.8% renal disease. The risk of death was significantly increased in patients with cardiac involvement [hazard ratio (HR) 3.15], with pulmonary interstitial disease (HR 2.58), with pulmonary hypertension (HR 3.50) and with renal manifestations (HR 2.76). A trend for survival improvement (R2)= 0.4295, P = 0.04) was found, and the difference in survival between the diffuse and limited scleroderma subgroups was diminishing (R2)= 0.4119. P = 0.02). Meta-analysis of observational studies indicates a trend for improvement over the last decades in which the life expectancy of SSc patients approaches that of the general population. A decreasing tendency in the survival differences between the limited and diffuse SSc subgroups was also verified. Internal organ involvements have similarly unfavourable predictive impact on survival.

Review from JAMA Internal Medicine — Use of New-Generation Oral Anticoagulant Agents in Patients Receiving Antiplatelet Therapy After an Acute Coronary Syndrome — Systematic Review and Meta-analysis of Randomized Controlled Trials

Cardiopulmonary manifestations have an important impact on the life expectancy of SSc patients. Functional and morphological macrovascular changes may appear early before the development of ischaemic symptoms. Several non-invasive methods are used in cardiovascular risk assessment. Heterogeneous data are available regarding these in SSc. We aimed to perform a systematic review and meta-analysis to characterize the importance of atherosclerosis in SSc. A systematic literature search was performed to identify controlled studies on carotid intima-media thickness, flow- or nitrate-induced vasodilatation (flow-mediated dilatation, nitroglycerine-mediated dilatation), pulse wave velocity, augmentation index and ankle-brachial pressure index. Outcomes were pooled with the random-effects model. Thirty-five studies comprising a total of 1292 SSc patients qualified. Intima-media thickness, pulse wave velocity and ankle-augmentation index were higher and flow-mediated dilatation lower in SSc patients [standardized mean difference (SMD) 0.65 (95% CI: 0.29, 1.01), 0.62 (95% CI: 0.35, 0.88), 0.96 (95% CI: 0.45, 1.47) and -0.68 (95% CI: -1.39, -0.34), respectively, P < 0.01 for each]. Nitroglycerine-mediated dilatation and ankle-brachial pressure index were lower, but not significantly [SMD: -0.16 (95% CI: -0.50, 0.18) and -0.39 (95% CI: -0.91, 0.13), respectively]. Data showed high to moderate inconsistency and significant heterogeneity. Meta-regression analysis of the SMD and the disease duration found a regression coefficient of 0.086, P = 0.014, confirming that parameters of the included SSc population may have contributed to the heterogeneity. Meta-analysis of the published observational studies confirms that abnormalities attributable to macrovascular involvement are significantly more prevalent in SSc patients compared with controls. Considering the increasing importance of cardiovascular disease in SSc, a more widespread use of cardiovascular risk assessment is warranted.

Objectives: Pulmonary arterial hypertension (PAH) is a common complication of systemic sclerosis (SSc). Symptoms of coronary artery disease (CAD) and PAH are closely related and cardiac catheterisation is needed to confirm their diagnosis. The aim of the present work was to investigate of the extent of overlap between CAD and PAH in patients with SSc. Methods: Based on non-invasive investigations, 20 patients out of 120 were suspected to have PAH (“suspected PAH” group). Another 10 patients showed signs of coronary disease (“suspected CAD” Group). In these 30 patients, right heart catheterisation and coronary angiography were performed, and the coronary flow reserve (CFR) was assessed by thermodilution technique. Results: In the “suspected PAH” and the “suspected CAD” groups, PAH was found in 12/20 and 2/10 cases, and coronary artery stenosis in 9/20 and 6/10 cases, respectively. Severely reduced CFR was revealed in 7/20 and 3/10 cases, respectively. Conclusions: PAH, CAD and reduced CFR all show a considerable overlap in symptomatic patients with SSc. The current non-invasive investigations are neither sensitive nor specific enough to make an appropriate distinction between these different disease manifestations. A more invasive approach, such as coronary angiography at the initial catheterisation, is required to properly characterise and treat the different forms of cardiac involvement in SSc.

Background: Despite numerous randomized clinical trials (RCT), data regarding the efficacy of antiplatelet and anticoagulant combinations are still conflicting. We aimed to analyze treatment options tested in various fields of cardiovascular prevention, regarding their efficacy and bleeding risk.Methods: Systematic searches of electronic databases were conducted until June 2022. A component network meta-analysis was performed in R. Risk estimates across trials were pooled using random-effects model selecting risk ratio (RR) with 95% confidence intervals (95% CIs) as summary statistics. The primary endpoint of interest was the rate of major cardiac adverse events (MACE). Major bleeding events were assessed as main safety endpoint. Secondary outcomes included cardiovascular- and overall mortality, myocardial infarction (MI), stent thrombosis, and stroke.Results: Fifteen studies randomizing 73,536 patients were identified. The MACE risk reflected heterogeneity among the anticoagulants with dabigatran and apixaban significantly reducing the risk of MACE (RR 0.56; 95% CI 0.39–0.80 and RR 0.75; 95% CI 0.58–0.98, respectively). Vitamin K antagonist (VKA), rivaroxaban, or edoxaban did not reduced of MACE while it was associated with a significant increase of bleeding risk (RR 1.66; 3.66, and 5.47, respectively). The direct anticoagulant (DOAC) dose reduction resulted in tendencies of fewer bleeding but higher MACE risk, while combination with aspirin was followed with increased risk for bleeding, however, remained non-significant in these cases.Conclusion: Our meta-analysis supports that the ischemic-bleeding balance is different among direct-acting oral anticoagulants (DOACs) while this is not significantly affected by the dose reduction approaches. Long-term aspirin treatment as part of the anticoagulant and dual antiplatelet regimen provides no ischemic benefit but may increase bleeding risk.Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [259703].

Background and Purpose: Preventive antiplatelet therapy is recommended for patients with cardiac or cerebrovascular atherosclerosis. Ticagrelor has an improved safety and efficacy profile in patients with acute coronary syndrome; however, data regarding stroke prevention remain controversial. We conducted a network meta-analysis to compare ticagrelor with other receptor antagonists (P2Y12) inhibitors and aspirin in monotherapy or combination in the treatment of patients with high risk for cardiovascular or cerebrovascular disease, defined as coronary artery disease, acute coronary syndrome, stroke or transient ischemic attack, or peripheral artery disease. Methods: Systematic searches of MEDLINE, EMBASE, and the Cochrane Library were conducted until August 1, 2020. Search terms included ticagrelor, AZD 6140, and stroke. The risk of bias was assessed using the Cochrane Collaboration assessment tool. Random-effects model was used to combine risk estimates across trials and risk ratio with 95% CIs served as summary statistics. The influence of individual components was evaluated in an additive network meta-analysis model. The primary efficacy end point was the occurrence of stroke. The safety end points included bleeding and all-cause mortality. Results: Twenty-six randomized clinical trials comprising 124 495 patients were analyzed. When compared with controls, ticagrelor plus aspirin significantly reduced the risk of ischemic stroke by 20% (risk ratio, 0.80 [95% CI, 0.71–0.89]). Treatment with ticagrelor monotherapy did not significantly affect ischemic stroke (risk ratio, 0.88 [95% CI, 0.77–1.00]; P =0.05). Compared with aspirin alone, major bleeding was in similar ranges with antiplatelet monotherapies while the relative risk was twice higher with combined antiplatelet therapies. There was no considerable difference in the risk of mortality with ticagrelor plus aspirin (risk ratio, 0.99 [95% CI, 0.91–1.07]). Conclusions: Ticagrelor on top of aspirin may provide more favorable outcomes on secondary stroke prevention in patients with vascular risk factors; however, this benefit may come with the price of increased bleeding risk including intracranial bleeding.